BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis ...BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response. to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.展开更多
Objective: The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis a...Objective: The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis and prognosis. Methods: To observe MRP-1/C9mRNA expression, tissue microarray (TMA) containing 54 lung cancers and 10 normal lung tissues was prepared and Fluorescence in situ hybridization was used. Results: The positive rate of MRP-1/CD9 expression was 48.1% in lung cancer, lower than that of normal lung tissues. The statistical difference was significant (P〈0.05). Its protein expression had no relationship with the patients' ages, sex and the macroscopic type of tumor, but had relationships with the histological type, clinical stage, differentiated degree and metastasis. The expression in non-small cell lung cancer (NSCLC) was higher than that in small cell lung cancer (SCLC); in well-moderately differentiated group was higher than that in poorly differentiated group; Earlier period group (I+II) was higher than in later period group (Ⅲ+Ⅳ); and in group without lymphoid metastasis was higher than in patients with lymphoid metastasis. Conclusion: The progression of the lung cancer maybe related with the descended MRP-1/Cd9 expression, which may be useful in evaluating the prognosis of cancer patients.展开更多
BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-canc...BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.展开更多
To investigate the expressions of survivin, PTEN and bFGF in lung cancer and precancerous lesion by tissue microarray technology. Methods: The expressions of Survivin, PTEN and bFGF were detected in 89 primary lung ca...To investigate the expressions of survivin, PTEN and bFGF in lung cancer and precancerous lesion by tissue microarray technology. Methods: The expressions of Survivin, PTEN and bFGF were detected in 89 primary lung cancers, 12 lung cancers with lymph node metastasis, 12 precancerous lesions of lung by an immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expression of Survivin and bFGF protein were 57.3% and 66.3% in 89 primary lung cancer respectively, significantly higher than the control group (P<0.05). The positive ratio of PTEN was 42.7% in primary lung cancer, significantly lower than that of nornmal tissue (90.0%)(P<0.05). The expressions of Survivin and bFGF were significantly related to lymph node metastasis and clinical stages. The expression of PTEN was related to differentiations, lymph node metastasis and clinical stages (P<0.05). There was a negative correlation between expressions of Survivin and PTEN, a positive correlation between expressions of Survivin and bGFG (P<0.01). Conclusion: Survivin, PTEN and bFGF proteins may be related to the pathogenesis, progression and malignant behavious of lung cancer, and there are some relationships between expressions of Survivin, PTEN and bFGF. Survivin, PTEN and bFGF may play a role in prognosis assessment of lung cancer.展开更多
Objective: XIAP-associated factor 1 (XAF1) expression has been shown to be related with apoptosis in hepatocellular carcinoma (HCC). However, the correlation of XAF1 expression with HCC tumor grade has not been i...Objective: XIAP-associated factor 1 (XAF1) expression has been shown to be related with apoptosis in hepatocellular carcinoma (HCC). However, the correlation of XAF1 expression with HCC tumor grade has not been intensively assessed. XIAP-associated factor-1 (XAF1) is an important apoptosis inducer in human HCC. The aim of this study is to determine the correlation between XAF1 expression and HCC histopathological grades. Methods: The mRNA levels of XAF1 in 24 paired HCC-nonneoplastic specimens were quantified by real-time reverse transcription PCR (RT-PCR). Protein levels of XAF1 in 110 paired HCC-noncancer tissues were investigated by immunostaining specimens on a tissue microarray (TMA). Correlations between XAF1 mRNA levels or protein expression and clinicopathological features were assessed by statistical analysis. Results: Both XAF1 mRNA and protein were significantly under-expressed in HCC tissues compared to their non-neoplastic counterparts. No significant relationship was found between XAF1 mRNA or protein expression and histological tumor grade. Conclusion: All these data suggest that XAF1 is a potential biomarker for differentiating HCC with noncancerous tissues.展开更多
S To provide evidences for exploiting tissue microarray (TMA) technology, we reviewed advantages and applications of TMA on tumor research. TMA has many advantages, including (1) section from TMA blocks can be utili...S To provide evidences for exploiting tissue microarray (TMA) technology, we reviewed advantages and applications of TMA on tumor research. TMA has many advantages, including (1) section from TMA blocks can be utilized for the simultaneous analysis of up to 1,000 different tumors at DNA, RNA or protein level; (2) TMA is highly representative of their donor tissues; (3) TMA can improve conservation of tissue resources and experimental reagents, improve internal experimental control, and increase sample numbers per experiment, and can be used for large-scale, massively parallel in situ analysis; (4) TMA facilitates rapid translation of molecular discoveries to clinical applications. TMA has been applied to tumor research, such as glioma, breast tumor, lung cancer and so on. The development of novel biochip technologies has opened up new possibilities for the high-throughput molecular profiling of human tumors. Novel molecular markers emerging from high-throughput expression surveys could be analyzed on tumor TMA. It is anticipated that TMA, a new member of biochip, will soon become a widely used tool for all types of tissue-based research. TMA will lead to a significant acceleration of the transition of basic research findings into clinical applications.展开更多
Objective: To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray (TMA) method. Methods: The expres...Objective: To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray (TMA) method. Methods: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH(fluorescence in situ hybridization) and immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expressions of Ets-1 rnRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group (P〈0.05). The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins (P〈0.05). Conclusion: Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.展开更多
Objective: The aim of this study was to investigate the Elk-1 (Ets like transcription factor-1) expression in non-small cell lung cancer (NSCLC) and normal lung tissues and the relationship between its expression...Objective: The aim of this study was to investigate the Elk-1 (Ets like transcription factor-1) expression in non-small cell lung cancer (NSCLC) and normal lung tissues and the relationship between its expression and clinicopathological characters. Methods: To observe Elk-1 expression, western blot and immunochemistry (IHC) on tissue microarray (TMA) containing 118 lung cancers and their corresponding normal tissues were used. Results: In western blot and IHC on TMA, Elk-1 was highly expressed in NSCLC, while its expression was almost undetectable in normal lung tissues. Elk- 1 expression in NSCLC had no relationship with the patients' age, gender, smoking status and histological type, but had relationship with the differentiation degree, clinical stages and lymphonode metastasis. The expression was lower in early stage group (Ⅰ+Ⅱ) than in advanced stage group (Ⅲ), and lower in well-moderately differentiated group than in poorly differentiated group. The same trend was seen with lymphonode metastasis. Conclusion: The progression of NSCLC may be related with the increased Elk-1 expression, and Elk-1 may be regarded as a prognostic factor for NSCLC tissues.展开更多
BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore th...BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.展开更多
AIM: To investigate let-7a expression and analyze the correlation between let-7a and progression of gastric mucosa cancerization. METHODS: The tissue microarray was constructed previously in 52 cases of human gastric ...AIM: To investigate let-7a expression and analyze the correlation between let-7a and progression of gastric mucosa cancerization. METHODS: The tissue microarray was constructed previously in 52 cases of human gastric carcinoma, 17 cases of chronic atrophic gastritis (atypical hyperplasia) and 11 cases of normal gastric tissue, and tissue microarrays combined with in situ hybridization were used to detect the expression of let-7a. RESULTS: The positive rates of let-7a in normal gastric tissue, chronic atrophic gastritis and gastric carcinoma were 90.9%, 88.2% and 86.5%, respectively, without significant differences among the groups (P > 0.05). However, an intense signal of let-7a was observed in gastric epithelial cells, whereas a less intense signal was found in gastric atypical hyperplasia epithelial cells anda weak signal in gastric carcinoma epithelial cells. The expression of let-7a decreased along with the progression of gastric mucosa cancerization (P < 0.05). In the group of gastric carcinoma, the expression of let-7a was even significantly lower in gastric carcinomas with lymph node metastasis than in those without metastasis (P < 0.05). CONCLUSION: Gastric carcinoma has relatively lower expression of let-7a. Reduced let-7a may be a fundamental factor in the formation and lymph node metastasis of gastric carcinoma.展开更多
Backgroud: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In thepresent study...Backgroud: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In thepresent study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCCprogression and outcome.展开更多
BACKGROUND:Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate.A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression wil...BACKGROUND:Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate.A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis,prevention,and treatment of this deadly disease.The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types.Currently,we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer.METHODS:IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues(adjacent tissues)by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry.The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed.RESULTS:Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues.Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer(80.0%,48/60)compared with adjacent tissues(18.3%,11/60)(P【0.001).Moreover,overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation(P【0.05).CONCLUSION:The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression,and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.展开更多
FANCD2 is involved in DNA damage repair and maintenance of chromosome stability.The purpose of this study was to investigate the expression of FANCD2 in sporadic breast cancer tissues and its association with clinicop...FANCD2 is involved in DNA damage repair and maintenance of chromosome stability.The purpose of this study was to investigate the expression of FANCD2 in sporadic breast cancer tissues and its association with clinicopathological features.A total of 162 Chinese women with invasive breast carcinoma who had no family history in first-degree relatives and 12 normal breast tissues were examined.The expression of FANCD2 was detected by immunohistochemical staining based on a tissue microarray technique.SAS system was used to analyze the data.Twenty-one out of the 162 invasive breast cancers(13%) were negative for FANCD2.The mean percentage of FANCD2 positive cells was significantly lower in breast cancers than in controls(P0.05).It was suggested that FANCD2 may play a critical role in breast carcinogenesis.It may become a valuable and independent marker for identifying women with sporadic breast cancer and evaluating the prognosis.展开更多
Objective:To investigate the significance of Poly(ADP-ribose) glycolhydrolase(PARG) and membrane type 1 matrix metalloproteinase(MT1-MMP) expressions in human colorectal carcinoma.Methods:Immunohistochemical s...Objective:To investigate the significance of Poly(ADP-ribose) glycolhydrolase(PARG) and membrane type 1 matrix metalloproteinase(MT1-MMP) expressions in human colorectal carcinoma.Methods:Immunohistochemical staining for PARG and MT1-MMP was carried out on colorectal adenoma-carcinoma tissue microarrays containing normal colorectal mucosae,adenoma,adenoma with malignant transformation and adenocarcinoma(total 130 specimens).The expressions of PARG and MT1-MMP in the GLTN [Gallotannin]-treated and GLTN-untreated lovo cells were detected by Western Blot.Results:PARG expression in adenocarcinoma(83.1%) and adenoma with malignant transformation(66.7%) was significantly higher than that in normal colorectal mucosa(10%) and adenoma(10.5%).Expression of MT1-MMp in normal colorectal mucosa and adenoma was negative,while the expression in adenocarcinoma(80.3%) and adenoma with malignant transformation(72.2%) was high.The expressions of PARG and MT1-MMP in adenocarcinoma with metastasis and in late tumor stages were significantly higher than those in adenocarcinoma with no metastasis and in early tumor stages.Thus,PARG expression shows a positive correlation with the expression of MT1-MMP.The expressions of PARG and MT1-MMP in GLTN-treated lovo cells were weaker than that in GLTN-untreated lovo cells.Conclusion:The expression of PARG was probably related to the development of colorectal carcinoma.PARG may play an important role for the regulation of MT1-MMP expression in colorectal carcinoma.展开更多
The role of histone modifications in the development and progression of cancer remains unclear. Here,we gave an investigation of the relationship between the various histone modifications and the risk prediction of th...The role of histone modifications in the development and progression of cancer remains unclear. Here,we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy (RP). Histone 3 lysine 4 dimethylation (H3K4diMe),trimethylation (H3K4triMe),lysine 36 trimethylation (H3K36triMe),histone 4 lysine 20 trimethylation (H4K20triMe)and acetylation of histome 3 lysine 9 (H3K9Ac) were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis (RPA) was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy,we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer (Gleason score≤6) after RP. In the case of high grade prostate cancer (Gleason score≥7),H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen (PSA) level could also predict the risk of the biochemical recurrence after RP. In combination with the Gieason score and pre-operation PSA level,the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.展开更多
BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer...BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer(PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS: EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues(P0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.展开更多
In the recent years,microarray technology gained attention for concurrent monitoring of numerous microarray images.It remains a major challenge to process,store and transmit such huge volumes of microarray images.So,i...In the recent years,microarray technology gained attention for concurrent monitoring of numerous microarray images.It remains a major challenge to process,store and transmit such huge volumes of microarray images.So,image compression techniques are used in the reduction of number of bits so that it can be stored and the images can be shared easily.Various techniques have been proposed in the past with applications in different domains.The current research paper presents a novel image compression technique i.e.,optimized Linde–Buzo–Gray(OLBG)with Lempel Ziv Markov Algorithm(LZMA)coding technique called OLBG-LZMA for compressing microarray images without any loss of quality.LBG model is generally used in designing a local optimal codebook for image compression.Codebook construction is treated as an optimizationissue and can be resolved with the help of Grey Wolf Optimization(GWO)algorithm.Once the codebook is constructed by LBGGWO algorithm,LZMA is employed for the compression of index table and raise its compression efficiency additionally.Experiments were performed on high resolution Tissue Microarray(TMA)image dataset of 50 prostate tissue samples collected from prostate cancer patients.The compression performance of the proposed coding esd compared with recently proposed techniques.The simulation results infer that OLBG-LZMA coding achieved a significant compression performance compared to other techniques.展开更多
BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,fi...BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative.MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein.MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer,which promotes the exploration of the correlation between MRPL35 and GC.We proposed that the expression of MRPL35 might be critical in GC.AIM To study the effect of MRPL35 knockdown on GC cell proliferation.METHODS The expression of MRPL35 in GC was evaluated based on data from the publictumor database UALCAN(www.ualcan.path.uab.edu).The effect of theexpression of MRPL35 on the prognosis was evaluated with KMplot(www.kmplot.com).The expression of MRPL35 was assessed on the tissuemicroarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairsof clinical GC tissues and matched adjacent tissues was detected by quantitativereverse transcription-polymerase chain reaction.Celigo cell count assay,colonyformation assay,and flow cytometry were used to assess the role of MRPL35 inGC cell proliferation and apoptosis in vitro.Additionally,tumor formationexperiment in BALB/c nude mice was utilized to determine the effect of MRPL35on GC cell proliferation.After knockdown of MRPL35,related proteins wereidentified by isobaric tags for relative and absolute quantification analysis,andthe expression of related proteins was detected by Western blot.RESULTSThe expression of MRPL35 was up-regulated in GC(P=1.77×10^(-4)).The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 wasassociated with a poor survival in GC.Compared with adjacent tissues,theexpression of MRPL35 in GC tissues was increased,which was related to age(P=0.03),lymph node metastasis(P=0.007),and pathological tumor-node-metastasisstage(P=0.024).Knockdown of MRPL35 inhibited GC cell proliferation andcolony formation and induced apoptosis.Animal experiment results showed thatknockdown of MRPL35 inhibited tumor formation in BALB/c nude mice.Westernblotting analysis showed that after knockdown of MRPL35,the expression ofPICK1 and BCL-XL proteins decreased,and that of AGR2 protein increased.CONCLUSIONCollectively,our findings demonstrate that knockdown of MRPL35 inhibits GCcell proliferation through related proteins including PICK1,BCL-XL,and AGR2.展开更多
Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study wer...Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue (P^O.O01) and was positively associated with higher Gleason score (P^O.O01) and higher prostate-specific antigen level (P=0.005). Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery (P=0.042) in the univariate analysis but not in the multivariate analysis (P=0. 139), which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.展开更多
文摘BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response. to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.
基金This work was supported by a grant from Tianjin Science and Technology Committee (No. 033804211)
文摘Objective: The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis and prognosis. Methods: To observe MRP-1/C9mRNA expression, tissue microarray (TMA) containing 54 lung cancers and 10 normal lung tissues was prepared and Fluorescence in situ hybridization was used. Results: The positive rate of MRP-1/CD9 expression was 48.1% in lung cancer, lower than that of normal lung tissues. The statistical difference was significant (P〈0.05). Its protein expression had no relationship with the patients' ages, sex and the macroscopic type of tumor, but had relationships with the histological type, clinical stage, differentiated degree and metastasis. The expression in non-small cell lung cancer (NSCLC) was higher than that in small cell lung cancer (SCLC); in well-moderately differentiated group was higher than that in poorly differentiated group; Earlier period group (I+II) was higher than in later period group (Ⅲ+Ⅳ); and in group without lymphoid metastasis was higher than in patients with lymphoid metastasis. Conclusion: The progression of the lung cancer maybe related with the descended MRP-1/Cd9 expression, which may be useful in evaluating the prognosis of cancer patients.
基金The study was supported by a grant from the National 863 program (2002AA2Z2021).
文摘BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.
基金This work was supported by a grant fromTianjin Provincial Science and Technology Committee (No.033804211)
文摘To investigate the expressions of survivin, PTEN and bFGF in lung cancer and precancerous lesion by tissue microarray technology. Methods: The expressions of Survivin, PTEN and bFGF were detected in 89 primary lung cancers, 12 lung cancers with lymph node metastasis, 12 precancerous lesions of lung by an immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expression of Survivin and bFGF protein were 57.3% and 66.3% in 89 primary lung cancer respectively, significantly higher than the control group (P<0.05). The positive ratio of PTEN was 42.7% in primary lung cancer, significantly lower than that of nornmal tissue (90.0%)(P<0.05). The expressions of Survivin and bFGF were significantly related to lymph node metastasis and clinical stages. The expression of PTEN was related to differentiations, lymph node metastasis and clinical stages (P<0.05). There was a negative correlation between expressions of Survivin and PTEN, a positive correlation between expressions of Survivin and bGFG (P<0.01). Conclusion: Survivin, PTEN and bFGF proteins may be related to the pathogenesis, progression and malignant behavious of lung cancer, and there are some relationships between expressions of Survivin, PTEN and bFGF. Survivin, PTEN and bFGF may play a role in prognosis assessment of lung cancer.
基金supported by grants from the National Natural Science Foundation of China (No. 30800186)Shanghai Natural Science Fundation (No. 11ZR1416800)
文摘Objective: XIAP-associated factor 1 (XAF1) expression has been shown to be related with apoptosis in hepatocellular carcinoma (HCC). However, the correlation of XAF1 expression with HCC tumor grade has not been intensively assessed. XIAP-associated factor-1 (XAF1) is an important apoptosis inducer in human HCC. The aim of this study is to determine the correlation between XAF1 expression and HCC histopathological grades. Methods: The mRNA levels of XAF1 in 24 paired HCC-nonneoplastic specimens were quantified by real-time reverse transcription PCR (RT-PCR). Protein levels of XAF1 in 110 paired HCC-noncancer tissues were investigated by immunostaining specimens on a tissue microarray (TMA). Correlations between XAF1 mRNA levels or protein expression and clinicopathological features were assessed by statistical analysis. Results: Both XAF1 mRNA and protein were significantly under-expressed in HCC tissues compared to their non-neoplastic counterparts. No significant relationship was found between XAF1 mRNA or protein expression and histological tumor grade. Conclusion: All these data suggest that XAF1 is a potential biomarker for differentiating HCC with noncancerous tissues.
文摘S To provide evidences for exploiting tissue microarray (TMA) technology, we reviewed advantages and applications of TMA on tumor research. TMA has many advantages, including (1) section from TMA blocks can be utilized for the simultaneous analysis of up to 1,000 different tumors at DNA, RNA or protein level; (2) TMA is highly representative of their donor tissues; (3) TMA can improve conservation of tissue resources and experimental reagents, improve internal experimental control, and increase sample numbers per experiment, and can be used for large-scale, massively parallel in situ analysis; (4) TMA facilitates rapid translation of molecular discoveries to clinical applications. TMA has been applied to tumor research, such as glioma, breast tumor, lung cancer and so on. The development of novel biochip technologies has opened up new possibilities for the high-throughput molecular profiling of human tumors. Novel molecular markers emerging from high-throughput expression surveys could be analyzed on tumor TMA. It is anticipated that TMA, a new member of biochip, will soon become a widely used tool for all types of tissue-based research. TMA will lead to a significant acceleration of the transition of basic research findings into clinical applications.
文摘Objective: To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray (TMA) method. Methods: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH(fluorescence in situ hybridization) and immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expressions of Ets-1 rnRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group (P〈0.05). The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins (P〈0.05). Conclusion: Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.
基金This project was supported by the National Natural Science Foundation of China (No. 30371624) the Scientific Research Foundation of Liaoning Education Office (No. 2004D157).
文摘Objective: The aim of this study was to investigate the Elk-1 (Ets like transcription factor-1) expression in non-small cell lung cancer (NSCLC) and normal lung tissues and the relationship between its expression and clinicopathological characters. Methods: To observe Elk-1 expression, western blot and immunochemistry (IHC) on tissue microarray (TMA) containing 118 lung cancers and their corresponding normal tissues were used. Results: In western blot and IHC on TMA, Elk-1 was highly expressed in NSCLC, while its expression was almost undetectable in normal lung tissues. Elk- 1 expression in NSCLC had no relationship with the patients' age, gender, smoking status and histological type, but had relationship with the differentiation degree, clinical stages and lymphonode metastasis. The expression was lower in early stage group (Ⅰ+Ⅱ) than in advanced stage group (Ⅲ), and lower in well-moderately differentiated group than in poorly differentiated group. The same trend was seen with lymphonode metastasis. Conclusion: The progression of NSCLC may be related with the increased Elk-1 expression, and Elk-1 may be regarded as a prognostic factor for NSCLC tissues.
文摘BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
基金Supported by Research Grants from the Key Science and Technology Projects of Guangxi Zhuang Autonomous Region
文摘AIM: To investigate let-7a expression and analyze the correlation between let-7a and progression of gastric mucosa cancerization. METHODS: The tissue microarray was constructed previously in 52 cases of human gastric carcinoma, 17 cases of chronic atrophic gastritis (atypical hyperplasia) and 11 cases of normal gastric tissue, and tissue microarrays combined with in situ hybridization were used to detect the expression of let-7a. RESULTS: The positive rates of let-7a in normal gastric tissue, chronic atrophic gastritis and gastric carcinoma were 90.9%, 88.2% and 86.5%, respectively, without significant differences among the groups (P > 0.05). However, an intense signal of let-7a was observed in gastric epithelial cells, whereas a less intense signal was found in gastric atypical hyperplasia epithelial cells anda weak signal in gastric carcinoma epithelial cells. The expression of let-7a decreased along with the progression of gastric mucosa cancerization (P < 0.05). In the group of gastric carcinoma, the expression of let-7a was even significantly lower in gastric carcinomas with lymph node metastasis than in those without metastasis (P < 0.05). CONCLUSION: Gastric carcinoma has relatively lower expression of let-7a. Reduced let-7a may be a fundamental factor in the formation and lymph node metastasis of gastric carcinoma.
基金supported by grants from the National Natural Science Foundation of China(81673241,81401988 and 81702419)Jiangsu Medical Science(BE2016698)+2 种基金Jiangsu Government Scholarship for Overseas Studies(JS-2014-209 and JS-2014-208)Projects of Nantong Health and Family Planning Commission Fund(WQ2016083)Jiangsu Graduate Innovation of China(KYCX17_1934)
文摘Backgroud: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In thepresent study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCCprogression and outcome.
基金supported by grants from the National Natural Science Foundation of China(81372676 and 30973401)the Natural Science Foundation of Shanxi Province(2009011052-1)
文摘BACKGROUND:Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate.A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis,prevention,and treatment of this deadly disease.The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types.Currently,we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer.METHODS:IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues(adjacent tissues)by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry.The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed.RESULTS:Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues.Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer(80.0%,48/60)compared with adjacent tissues(18.3%,11/60)(P【0.001).Moreover,overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation(P【0.05).CONCLUSION:The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression,and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.
文摘FANCD2 is involved in DNA damage repair and maintenance of chromosome stability.The purpose of this study was to investigate the expression of FANCD2 in sporadic breast cancer tissues and its association with clinicopathological features.A total of 162 Chinese women with invasive breast carcinoma who had no family history in first-degree relatives and 12 normal breast tissues were examined.The expression of FANCD2 was detected by immunohistochemical staining based on a tissue microarray technique.SAS system was used to analyze the data.Twenty-one out of the 162 invasive breast cancers(13%) were negative for FANCD2.The mean percentage of FANCD2 positive cells was significantly lower in breast cancers than in controls(P0.05).It was suggested that FANCD2 may play a critical role in breast carcinogenesis.It may become a valuable and independent marker for identifying women with sporadic breast cancer and evaluating the prognosis.
基金supported by the National Natural Science Foundation of China(No.30870946)Research Foundation of Chongqing Medical University(XB0536)
文摘Objective:To investigate the significance of Poly(ADP-ribose) glycolhydrolase(PARG) and membrane type 1 matrix metalloproteinase(MT1-MMP) expressions in human colorectal carcinoma.Methods:Immunohistochemical staining for PARG and MT1-MMP was carried out on colorectal adenoma-carcinoma tissue microarrays containing normal colorectal mucosae,adenoma,adenoma with malignant transformation and adenocarcinoma(total 130 specimens).The expressions of PARG and MT1-MMP in the GLTN [Gallotannin]-treated and GLTN-untreated lovo cells were detected by Western Blot.Results:PARG expression in adenocarcinoma(83.1%) and adenoma with malignant transformation(66.7%) was significantly higher than that in normal colorectal mucosa(10%) and adenoma(10.5%).Expression of MT1-MMp in normal colorectal mucosa and adenoma was negative,while the expression in adenocarcinoma(80.3%) and adenoma with malignant transformation(72.2%) was high.The expressions of PARG and MT1-MMP in adenocarcinoma with metastasis and in late tumor stages were significantly higher than those in adenocarcinoma with no metastasis and in early tumor stages.Thus,PARG expression shows a positive correlation with the expression of MT1-MMP.The expressions of PARG and MT1-MMP in GLTN-treated lovo cells were weaker than that in GLTN-untreated lovo cells.Conclusion:The expression of PARG was probably related to the development of colorectal carcinoma.PARG may play an important role for the regulation of MT1-MMP expression in colorectal carcinoma.
文摘The role of histone modifications in the development and progression of cancer remains unclear. Here,we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy (RP). Histone 3 lysine 4 dimethylation (H3K4diMe),trimethylation (H3K4triMe),lysine 36 trimethylation (H3K36triMe),histone 4 lysine 20 trimethylation (H4K20triMe)and acetylation of histome 3 lysine 9 (H3K9Ac) were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis (RPA) was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy,we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer (Gleason score≤6) after RP. In the case of high grade prostate cancer (Gleason score≥7),H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen (PSA) level could also predict the risk of the biochemical recurrence after RP. In combination with the Gieason score and pre-operation PSA level,the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.
基金supported by a grant from the Research Special Fund for Public Welfare Industry of Health(201202007)
文摘BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7(EGFL7)in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer(PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally,correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.RESULTS: EGFL7 was widely expressed in all PC cell lines tested.EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues(P0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival,accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for longterm outcome of PC.CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.
文摘In the recent years,microarray technology gained attention for concurrent monitoring of numerous microarray images.It remains a major challenge to process,store and transmit such huge volumes of microarray images.So,image compression techniques are used in the reduction of number of bits so that it can be stored and the images can be shared easily.Various techniques have been proposed in the past with applications in different domains.The current research paper presents a novel image compression technique i.e.,optimized Linde–Buzo–Gray(OLBG)with Lempel Ziv Markov Algorithm(LZMA)coding technique called OLBG-LZMA for compressing microarray images without any loss of quality.LBG model is generally used in designing a local optimal codebook for image compression.Codebook construction is treated as an optimizationissue and can be resolved with the help of Grey Wolf Optimization(GWO)algorithm.Once the codebook is constructed by LBGGWO algorithm,LZMA is employed for the compression of index table and raise its compression efficiency additionally.Experiments were performed on high resolution Tissue Microarray(TMA)image dataset of 50 prostate tissue samples collected from prostate cancer patients.The compression performance of the proposed coding esd compared with recently proposed techniques.The simulation results infer that OLBG-LZMA coding achieved a significant compression performance compared to other techniques.
文摘BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative.MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein.MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer,which promotes the exploration of the correlation between MRPL35 and GC.We proposed that the expression of MRPL35 might be critical in GC.AIM To study the effect of MRPL35 knockdown on GC cell proliferation.METHODS The expression of MRPL35 in GC was evaluated based on data from the publictumor database UALCAN(www.ualcan.path.uab.edu).The effect of theexpression of MRPL35 on the prognosis was evaluated with KMplot(www.kmplot.com).The expression of MRPL35 was assessed on the tissuemicroarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairsof clinical GC tissues and matched adjacent tissues was detected by quantitativereverse transcription-polymerase chain reaction.Celigo cell count assay,colonyformation assay,and flow cytometry were used to assess the role of MRPL35 inGC cell proliferation and apoptosis in vitro.Additionally,tumor formationexperiment in BALB/c nude mice was utilized to determine the effect of MRPL35on GC cell proliferation.After knockdown of MRPL35,related proteins wereidentified by isobaric tags for relative and absolute quantification analysis,andthe expression of related proteins was detected by Western blot.RESULTSThe expression of MRPL35 was up-regulated in GC(P=1.77×10^(-4)).The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 wasassociated with a poor survival in GC.Compared with adjacent tissues,theexpression of MRPL35 in GC tissues was increased,which was related to age(P=0.03),lymph node metastasis(P=0.007),and pathological tumor-node-metastasisstage(P=0.024).Knockdown of MRPL35 inhibited GC cell proliferation andcolony formation and induced apoptosis.Animal experiment results showed thatknockdown of MRPL35 inhibited tumor formation in BALB/c nude mice.Westernblotting analysis showed that after knockdown of MRPL35,the expression ofPICK1 and BCL-XL proteins decreased,and that of AGR2 protein increased.CONCLUSIONCollectively,our findings demonstrate that knockdown of MRPL35 inhibits GCcell proliferation through related proteins including PICK1,BCL-XL,and AGR2.
基金This study was supported by the National Basic Research Program of China (No. 2012CB518300), the National Natural Science Foundation of China(No. 81101946), the Prostate Cancer Foundation Young Investigator Award, the Shanghai Pujiang Program (No. 12PID008) and the Key Project of Science and Technology Commission of Shanghai Municipality (No. 09DJ 1400400).
文摘Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue (P^O.O01) and was positively associated with higher Gleason score (P^O.O01) and higher prostate-specific antigen level (P=0.005). Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery (P=0.042) in the univariate analysis but not in the multivariate analysis (P=0. 139), which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.