Positive expression and correlation of chemokine receptor CXCR4 with nodal metastasis and prognosis in colorectal cancer

Objective: Colorectal cancer is one of the leading causes of cancer related deaths, with recurrence and metasta- sis as the primary reasons for mortality. New evidence has implicated chemokines as the likely cause. We studied the positive expression of CXCR4 chemokine receptors in colorectal carcinoma and investigated its correlations to clinicpathological char- acteristics and prognosis. Methods: Tumor tissue specimens of patients with colorectal carcinoma (n = 67) who underwent surgery from January 2003 to December 2004 at the Department of Surgery, Tongji Hospital were collected. CXCR4 expres- sion levels and tumor microvessel density were evaluated by immunohistochemistry. Specimens were immunostained using formalin-fixed, paraffin-embedded tissues. The correlation between the CXCR4 expression and clinicopathological factors was evaluated. Results: In 67 cancer tissue specimens, CXCR4 was positively expressed in 38 cases, positive rate being 56.7%. Positive expression of CXCR4 is associated with an increasing incidence of nodal involvement, higher clinic stage, higher tumor microvessel density and a lower 3-year disease free survival rate as compared to those with negative CXCR4 expression (P < 0.05). Conclusion: Positive CXCR4 expression and high tumor microvessel density are associated with poor prognosis and could be a potential predictive factor for recurrence or metastasis of colorectal cancer patients. So CXCR4 may be a potential target for specific therapeutic interventions in the future.

Differential mucin phenotypes and their significance in a variation of colorectal carcinoma

AIM: To investigate mucin expression profiles in colorectal carcinoma (CRC) histological subtypes with regard to clinicopathologic variables and prognosis. METHODS: Mucin (MUC)2 and MUC5AC expressions were assessed by immunohistochemistry for a total of 250 CRC cases that underwent surgical resection. CRCs included 63 well-to-moderately differentiated adenocar-cinomas (WMDAs), 91 poorly differentiated adenocarcinomas (PDAs), 81 mucinous adenocarcinoma (MUAs), and 15 signet-ring cell carcinomas (SRCCs). MUC2 and MUC5AC were scored as positive when ≥ 25% and ≥ 1% of cancer cells were stained positive, respectively. The human mutL homolog 1 and human mutS homolog 2 expressions were assessed by immunohistochemistry in PDAs to investigate mismatch-repair (MMR) status.Tumors that did not express either of these two were considered MMR-deficient. Results were analyzed for associations with clinicopathologic variables and the prognosis in individual histological CRC subtypes. RESULTS: MUC2-positive and MUC5AC-positive WMDA percentages were 49.2% and 30.2%, respectively. In contrast, MUC2-positive and MUC5AC-positive PDA percentages were 9.5% and 51.6%, respectively. MUC2 levels tended to decrease and MUC5AC levels tended to increase from WMDA to PDA. In 21 tumors comprising both adenoma and adenocarcinoma components in a single tumor (4 WMDAs, 7 PDAs, and 10 MUAs), MUC2 was significantly downregulated in PDA and MUC5AC was downregulated in PDA and MUA in the adenoma-carcinoma sequence. These results suggested that MUC2 levels might be associated with malignant potential and that MUC5AC expression was an early event in tumorigenesis. Despite worse prognoses than WMDA, high MUC2 expression levels were maintained in MUA (95.1%) and SRCC (71.5%), which suggested a pathogenesis for these subtypes distinct from that of WMDA. No significant associations were found between MUC2 expression and any clinicopathologic variables in any histological subtype. MUC5AC expression in PDA was closely associated with right-sided location (P = 0.017), absence of nodal metastasis (P = 0.010), low tumor node metastasis stage (P = 0.010), and MMR deficiency (P = 0.003). MUC2 expression in WMDA was a marginal prognostic factor for recurrence/metastasis-free survival (RFS) by univariate Cox analysis (P = 0.077) but not by multivariate Cox analysis (P = 0.161). MUC5AC expression in PDA was a significant prognostic factor for RFS by univariate Cox analysis (P = 0.007) but not by multivariate Cox analysis (P = 0.104). Kaplan-Meier curves and log-rank tests revealed that MUC2 expression was marginally associated with a better WMDA prognosis [P = 0.064 for RFS and P = 0.172 for overall survival (OS)] but not for PDA. In contrast, MUC5AC expression was significantly and marginally associated with a better PDA prognosis in terms of RFS and OS, respectively(P = 0.004 for RFS and P = 0.100 for OS), but not for WMDA and MUA. CONCLUSION: Mucin core protein expression profiles and clinical significance differ according to histological CRC subtypes. This may reflect different pathogeneses for these tumors.

E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome

AIM： To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS： E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations （membrane and cytoplasm）. Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free （DFS） and disease-specific （DSS） survival. RESULTS： E-cadherin membrane index （MI）, but not cytoplasmic index （CI）, was significantly higher in primary tumors than their metastases （P = 0.0001）. Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis （P = 0.022 and P = 0.007, respectively）. Interestingly, both indices were higher in liver metastase compared to other anatomic sites （MI, P = 0.034 and CI, P = 0.022）. The CI of the primary tumors was a significant predictor of DFS （P = 0.042, univariate analysis）, with a strong inverse correlation between CI and DFS （P = 0.006, multivariate analysis）. Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome （P = 0.016）. CONCLUSION： Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma

AIM:To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using X2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P=0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P= 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P= 0.012), and the performance status (P=0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.

Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

AIM： To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer （CRC）. METHODS： Archival tumor samples were analyzed for β-catenin using immunohistochemistry （IHC） in 95 patients with advanced CRC. RESULTS： Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 （58%） cases showed nuclear expression. In univariate （Kaplan-Meier） survival analysis, only the nuclear index （NI） was a significant predictor of disease free survival （DFS） （P = 0.023; n = 35）, with a NI above the median associated with longer DFS （34.2 too） than those with a NI below the median （15.5 too） （P = 0.045, ANOVA）. The other indices were not significant predictors of DFS, and none of the three tested indices （for membranous, cytoplasmic, or nuclear expression） predicted diseasespecific survival （DSS）. However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS （P = 0.041） and DSS （P = 0.046）. CONCLUSION： Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

Objective: This study was designed to detect the expression of bcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Methods: Immunohistochemistry method was used to detect the expression of bcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Results: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(?) had the best prognosis. This group was significantly associated with earlier Dukes’ stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. Conclusion: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

Epithelial membrane protein 1 negatively regulates cell growth and metastasis in colorectal carcinoma

AIM: To determine the expression and function of epithelial membrane protein 1 (EMP1) in colorectal carcinoma.

Clinical significance of subcellular localization of KL-6 mucin in primary colorectal adenocarcinoma and metastatic tissues

AIM： To assess subcellular localization of KL-6 mucin and its clinicopathological significance in colorectal carcinoma as well as metastatic lymph node and liver tissues. METHODS： Colorectal carcinoma tissues as well as metastatic lymph node and liver tissues were collected from 82 patients who underwent colorectomy or hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS： Of the 82 colorectal carcinoma patients, 6 showed no staining, 29 showed positive staining only in the apical membrane, and 47 showed positive staining in the circumferential membrane and/or cytoplasm. Positive staining was not observed in non-cancerous colorectal epithelial cells surrounding the tumor tissues. The five-year survival rate was significantly lower in cases showing positive staining in the circumferential membrane and/or cytoplasm （63.0%） than those showing positive staining only in the apical membrane （85.7%） and those showing no staining （100%）. Statistical analysis between clinicopathological factors and subcellular localization of KL-6 mucin showed that KL-6 localization in the circumferential membrane and/or cytoplasm was significantly associated with the presence of venous invasion （P = 0.0003）, lymphatic invasion （P 〈 0.0001）, lymph node metastasis （P〈0.0001）, liver metastasis （P = 0.058）, and advanced histological stage （P〈 0.0001）. Positive staining was observed in all metastatic lesions tested as well as in the primary colorectal carcinoma tissues. CONCLUSION： The subcellular staining pattern of KL-6 in colorectal adenocarcinoma may be an important indicator for unfavorable behaviors such as lymph node and liver metastasis, as well as for the prognosis of patients.

Prognostic value of YKL-40 in colorectal carcinoma patients:A metaanalysis

BACKGROUND In recent years,the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated.However,whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified.AIM To identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients.METHODS Several electronic databases including the PubMed,EMBASE,Web of Science,CNKI,VIP and WanFang were searched for relevant studies.The hazard ratios(HR)and 95%confidence intervals(CI)were combined and the primary and secondary outcomes were overall survival(OS)and progression-free survival(PFS),respectively.All statistical analysis were conducted by STATA 15.0 software.RESULTS A total of nine studies involving 2545 patients were included.The pooled results indicated that YKL-40 was significantly associated with poor OS(HR=1.80,95%CI:1.32-2.45,P<0.001)and PFS(HR=1.62,95%CI:1.22-2.16,P=0.001).Subgroup analysis stratified by the treatment,tumor type and source of YKL-40 showed similar results.CONCLUSION Elevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients.YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.

SERUM INTERLEUKIN-18 LEVEL AS A PROGNOSTIC MARKER IN PATIENTS WITH COLORECTAL CARCINOMA

Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.

Role of microsatellite instability in occurrence of colorectal carcinoma and its prognostic significance

Objective: To explore the role of microsatellite instability (MSI ) in the occurrence of colorectal carcinoma and the relationship between MSI and prognosis of the carcinoma. Methods: MSI at 6 loci of D18S34. D17S799. D55409. TCF--2, P53 and Rb in 56 cases of colorectal carcinoma were detected with PCRSSLP. Results: The total positive rate of MSI was 44. 64 %. The 3-or 5-year survival rate was higher in the cases with MSI than in those without. Conclusion: MSI may be another molecular mechanism of occurrence of colorectal carcinoma. The cases of colorectal carcinoma with MSI have better biological behavior and outcome. Therefore. the detection of MSI might be useful for prediction of the prognosis of colorectal carcinoma.

Prognostic nomograms for predicting overall survival and causespecific survival of signet ring cell carcinoma in colorectal cancer patients

BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

AIM： To examine the expression of beta-catenin in colorectal cancer and look for association with other dinico-pathological parameters. METHODS;： Tumor samples from 163 cases of colorectal cancer （CRC） who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density （OSD） and percentage of cells having nuclear localization was counted as nuclear staining density （NSD）. Univariate exploration used log-rank test and multivariate survival analysis used Cox＇s hazard regression model. RESULTS： Beta-catenin immunoreactivity was detected in 161 samples （98.8%）, of which 131 cases had nuclear staining. High OSD （≥ 75%）, detected in 123 cases （75.5%）, was significantly associated with earlier clinical staging （P 〈 0.01）, lower nodal status （P = 0.02）, non-metastatic status （P 〈 0.01） and better differentiation （P = 0.02）. Multivariate analysis found that high OSD was independently associated with better survival [Cox＇s hazard ratio 0.51, 95% confidence interval （CI） 0.31-0.83]. Although high NSD （≥ 75%） was correlated with high pre-operative serum CEA （P = 0.03）, well differentiation （P 〈 0.01）, and increased staining intensity（P 〈 0.01）, the parameter was not significantly associated with survival. CONCLI3SIOM： Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.

Importance of MutL homologue MLH1 and MutS homologue MSH2 expression in Turkish patients with sporadic colorectal cancer

AIM： To assess the incidence of MLH1 （the human MutL homologue） and MSH2 （the human MutS homologue） protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features. METHODS： We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis： p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability （MSI）. RESULTS： Our analysis showed that 29 （39.2%） had loss of MLH1 expression, 5 （6.8%） had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival （71.7 ± 8.65 mo vs 47.08± 5.26 too） for the patients with MLHl-negative versus MLHl-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and -negative cases.CONCLUSION： Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas.

Death decoy receptor overexpression and increased malignancy risk in colorectal cancer

AIM: To evaluate human epidermal growth factor receptor 2 (HER2) and death decoy receptor (DcR3) as colorectal cancer prognostic indicators.

Up-regulation of α-catenin is associated with increased lymph node involvement in colorectal cancer

AIM: To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients. METHODS: Archival tumor samples were analyzed using immunohistochemistry (IHC) for α-catenin in 91 patients with advanced CRC. RESULTS: The values of α-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high α-catenin expression had a signifi cantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longerSWM, but no such effect on disease free survival (DFS) or disease specifi c survival (DSS). As to co-expression with another member of the adhesion complex (β-catenin), high α-catenin/β-catenin MI index was of marginal signifi cance in predicting longer DSS (P = 0.063, log-rank). CONCLUSION: The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.

Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma

Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation.However,few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma （CRC）.This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms.Methods The 40 CRC,adjacent nontumorous tissues and 2 human CRC-derived cell lines （SW-480 and SW-620） were collected,respectively,and the total RNA and protein were isolated routinely.The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction （RT-PCR） and Northern blotting.Smoothened （SMO,possible target of miR-338-3p） mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting.miR-338-3p expression patterns were compared between nontumor mucosa and CRC samples,graded by progression-related factors.Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival （DFS） and overall survival （OS） of patients.Moreover,SMO 3＇-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid.The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected.Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues,and the value was negatively related to advanced TNM stage and local invasion （P ＜0.01）.Furthermore,miR338-3p value was decreased markedly in SW-620 cell line relative to SW-480 （P ＜0.01）.Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates.Moreover,RT-PCR and Western blotting analysis demonstrated that there was no significant difference in SMO mRNA expression between the corresponding CRCs and nontumorous tissues,whereas SMO protein markedly increased in CRCs （P ＜0.01）.A significant increase in luciferase activity was detected in CRC cells,which were cotransfected with the luciferase reporter plasmid construct and anti-miR-338-3p （P ＜0.01）.Conclusions miR-338-3p is expressed differentially in CRC and associated with progression and prognosis of CRC.SMO might be a possible target of miR-338-3p,which made it a potential antitumor candidate for treatment and prevention of CRC.

结直肠癌组织中SEC62、LSM12表达与临床病理参数、上皮间质转化及预后的关系

目的分析结直肠癌(CRC)组织中前蛋白易位因子(SEC62)、RNA剪切因子(LSM12)表达与临床病理参数、上皮间质转化(EMT)及预后的关系。方法选取92例CRC患者,术中收集CRC组织及癌旁组织。用实时荧光定量PCR法检测SEC62、LSM12 mRNA及EMT相关基因[E-钙黏蛋白(E-cadherin/N-钙黏蛋白(N-cadherin)、Twist转录因子(TWIST)基因],用免疫组化法检测SEC62、LSM12蛋白。分析结直肠癌组织中SEC62、LSM12 mRNA表达与临床病理参数、EMT相关基因的关系。从癌症基因组图谱数据库(TCGA,https://portal.gdc.cancer.gov)下载643例CRC患者的癌组织RNAseq数据,分析SEC62、LSM12 mRNA表达与CRC患者5年总生存率的关系。结果与癌旁组织比较,CRC组织中SEC62、LSM12、N-cadherin、TWIST mRNA表达高,E-cadherin mRNA表达低,SEC62、LSM12蛋白阳性表达率高,差异均有统计学意义(P均<0.05)。不同TNM分期、分化程度及有无淋巴结转移的CRC组织中SEC62、LSM12 mRNA表达比较差异有统计学意义(P均<0.05)。CRC组织中SEC62 mRNA表达与N-cadherin、TWIST mRNA表达呈正相关(r分别为0.643、0.721,P均<0.05),与E-cadherin mRNA表达呈负相关(r=-0.684,P<0.05)。CRC组织中LSM12 mRNA表达与N-cadherin、TWIST mRNA表达呈正相关(r分别为0.715、0.786,P均<0.05),与E-cadherin mRNA表达呈负相关(r=-0.687,P<0.05)。根据SEC62、LSM12 mRNA表达的中位数将TCGA中643例CRC患者分为SEC62 mRNA高表达者(>3.12,n=322)、低表达者(≤3.12,n=321),LSM12 mRNA高表达者(>2.57,n=321)、低表达者(≤2.57,n=322)。SEC62 mRNA高表达者5年总生存率低于SEC62 mRNA低表达者(Log-rankχ^(2)=5.960,HR=1.547,95%CI:1.225~1.820,P<0.05);LSM12 mRNA高表达者5年总生存率低于LSM12 mRNA低表达者(Log-rankχ^(2)=6.012,HR=1.649,95%CI:1.253~1.834,P<0.05)。结论CRC组织中SEC62、LSM12高表达,二者表达变化与肿瘤TNM分期、分化程度、淋巴结转移、EMT及预后有关。

结直肠癌组织PAX8、SFRP4表达水平及与患者临床病理特征、预后的相关性研究

目的探究结直肠癌(CRC)组织配对盒基因8(PAX8)和分泌型卷曲相关蛋白4(SFRP4)表达水平与患者临床病理特征及预后的相关性研究。方法前瞻性选取2019年1月至2021年10月西安交通大学医学院附属陕西省肿瘤医院病理科就诊的125例CRC患者在手术中切除的CRC组织及癌旁组织(距离CRC组织>2 cm)标本。收集整理CRC患者年龄、性别、糖尿病、高血压、组织学分型、肿瘤部位、附件转移、淋巴结转移、肿瘤淋巴结转移(TNM)分期、组织分级、淋巴结状态、肿瘤直径等临床资料。采用免疫组织化学染色法(IHC)检测PAX8和SFRP4表达水平;采用Spearman等级相关分析对癌组织PAX8和SFRP4表达的相关性进行分析;采用Kaplan-Meier法进行CRC患者预后生存分析。结果PAX8和SFRP4在癌组织的高表达率为64.80%、59.20%,均高于癌旁组织(32.80%、36.80%),差异均有统计学意义(P<0.05),且两者的表达具有相关性(r=0.479,P<0.05)。PAX8和SFRP4表达与年龄、性别、糖尿病、高血压、组织学分型、肿瘤部位、附件转移、肿瘤直径等无关,差异均无统计学意义(P>0.05);PAX8和SFRP4表达与淋巴结转移、TNM分期、组织分级、淋巴结状态有关,差异均有统计学意义(P<0.05)。高表达PAX8和SFRP4的CRC患者术后2年预后不良率分别为37.04%和37.84%,均高于低表达PAX8和SFRP4(15.91%、17.65%),差异均有统计学意义(P<0.05)。结论PAX8和SFRP4在CRC组织中高表达,且两者具有一定的相关性,高表达的PAX8和SFRP4可作为CRC患者预后不良的重要指标。

应用Ag-NOR计数、DNA含量检测大肠癌的预后价值

该文应用胶质银染技术、自动图像分析仪DNA含量测量技术对56例大肠癌手术标本进行了检测。结果发现Ag－NOR计数与患者存活时间呈负相关（r＝－0．77P＜0．001）。Ag－NOR计数低，患者存活时间长，预后好；反之则预后差。对数秩时序检验P＜0．001。在DNA含量总体直方图中，大肠癌细胞DNA主峰位于2～6C之间，预后好组，其主峰左移至2C附近，大于5C细胞群较少（10．48±9．89），而预后差组主峰右移至5C附近，大于5C细胞所占比例明显增多（61．59±21．45）。2C细胞群为主大肠癌Ag－NOR计数（4．04±0．66）低于以非整倍体细胞群占多数大肠癌（5．92±1．49）（P＜0．01）。结合运用上述指标可提高判断预后的准确性。