Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer

The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

HER2 gene status and the relationship with p21 protein expression in gastric cancer

Objective： We aimed to analysis the HER2 gene status and its relationship with p21 protein expression in gastric carcinoma. Methods： Fluorescence in situ hybridisation （FISH） and immunohistochemistry （IHC） techniques were used to detect HER2 gene status and p53 protein in 59 cases of gastric cancer. Results： FISH detection of HER2 gene amplification rate was 16.9% （10/59）, HER2 gene amplification in 49 cases without copy number gain and gene amplification were a total of 49.2% （29/59）. HER2 protein expression was 42.4% （25/59）, HER2 gene amplification rates in patients with ＋＋＋, ＋＋ HER2 protein expression were 3/3 and 5/8, while in patients with ＋ HER2 protein expression, it was 2/14, there was significant difference （P 0.05）. p21 protein expression rate was 49.2% （29/59）, HER2 gene amplification rates and p21 protein expression had significant difference in tumor invasion depth, lymph node metastasis （P 0.05）; had no statistical significance in histological type, age, gender differences （P 0.05）. Conclusion： HER2 gene amplification rate and gene copy number had positively correlation with p21 protein expression, HER2 gene status and expression of p21 protein combined detection can provide a reference value in gastric cancer metastasis, patient’s condition development and prognosis, it also can guide clinical development of individual treatment.

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

AIM:To investigate the association between the tag single nucleotide polymorphisms(TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.METHODS:We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls.Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system.The serum levels of anti-Helicobacter pylori(H.pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection.The odds ratios(OR) and 95% confidence intervals(CI) were calculated by unconditional logistic regression,including sex and age as confounding factors.RESULTS:The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer(OR 0.50,95% CI:0.26-0.95,P = 0.04) while the rs7789045 TT genotype showed an increased risk(OR 2.14,95% CI:1.20-3.82,P = 0.01).An elevated susceptibility to gastric cancer was observed in the subjects with H.pylori infection and the NaOD1 rs7789045 TT genotype(OR 2.05,95% CI:1.07-3.94,P = 0.03) or the NOD2 rs7205423 GC genotype(OR 2.52,95% CI:1.05-6.04,P = 0.04).Haplotype analysis suggested that the distribution of AGT(rs2907749,rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different(P corrected:0.04),and the diplotype AGT/AGT was associated with an elevated gastric cancer risk(OR 1.98,95% CI:1.04-3.79,P = 0.04).The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H.pylori-related diffuse-type gastric cancer(OR 3.00,95% CI:1.38-6.53,P = 0.01;OR 4.02,95% CI:1.61-10.05,P < 0.01,respectively).CONCLUSION:Genetic polymorphisms in NOD1 and NOD2 may interact with H.pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.

Genetic polymorphisms of N-acetyltransferase 2 and colorectal cancer risk

AIM： To identify the distribution of N-acetyltrasferase 2 （NAT2） polymorphism in Hebei Han Chinese and the effects of the polymorphism on the development of colorectal cancer.METHODS： We performed a hospital-based case-control study of 237 healthy individuals and 83 colorectal cancer patients of Hebei Han Chinese. DNA was extracted from peripheral blood and cancer tissues. The genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism（RFLP）.RESULTS： There were four NAT2 alleles of WT, M1, M2,and M3 both in the healthy subjects and in the patients,and 10 genotypes of WT/WT, WT/M1, WT/M2, WT/M3,M1/M1, M1/M2, M1/M3, M2/M2, M2/M3, M3/M3. M2 allele was present in 15.61% of healthy subjects and 29.52% of patients （X^2 = 15.31, P〈0.0001）, and M3 allele was present in 30.59% of healthy subjects and 16.87% of patients （X^2 = 25.33, P〈0.0001）. There were more WT/M2 （X^2= 34.42, P〈0.0001, odd ratio= 4.99, 95%CI = 2.27-9.38）and less WT/M3 （X^2 = 3.80, P = 0.03） in the patients than in the healthy subjects. In 70.3% of the patients, there was a difference in NAT2 genotype between their tumors and blood cells. Patients had more WT/M2 （7.2 = 5.11,P = 0.02） and less M2/M3 （X^2= 4.27, P = 0.039） in their blood cells than in the tumors. Furthermore, 53.8% （7/13）of M2/M3 in tumors were from VVT/M2 of blood cells.CONCLUSION： There is a possible relationship between the NAT2 polymorphisms and colorectal cancer in Hebei Han Chinese. The genotype WT/M2 may be a risk factor for colorectal cancer.

N-myc downstream-regulated gene 2 promotes proliferation of HO-8910 ovarian cancer cells

Objective To investigate N-myc downstream-regulated gene 2(NDRG2) expression in ovarian cancer cells and its potential usefulness as a diagnostic marker and/or target for therapeutic intervention.Methods Human NDRG2 L/S gene was obtained by revers-transcription polymerase chain reaction(RT-PCR). Sequence analysis confirmed the identity of NDRG2 L/S gene, which was then inserted into a eukaryotic vector p LNCX2, which was in turn transfected into NDRG2 gene-negative HO-8910 cells. Flow cytometry(FCM) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay were conducted to determine the proliferation rate of HO-8910 cells. Cisplatin resistance of HO-8910 cells transfected with p LNCX2-NDRG2 L/S was evaluated by FCM. Tumors were generated in female nude mice by subcutaneous injection of HO-8910 cells.Results NDRG2 gene was isolated and its expression vector was successfully constructed. NDRG2 expression positively correlated with the proliferation of HO-8910 cells. NDRG2 L/S promoted tumorigenicity in HO-8910 cells.Conclusion The present study identified a novel function of NDRG2 L/S gene and demonstrated its involvement in the promotion of ovarian cancer cell proliferation and enhancement of cisplatin resistance in HO-8910 cells. Future studies are warranted to determine the relationship between NDRG2 upregulation and ovarian cancer progression.

The expression of HER-2/neu gene in colon cancer tissues and its clinical significance

Objective：The article aims to detect the expression of HER-2/neu gene in colon cancer tissues and adjacent tissues, to analyze the relationship between dif erent pathologic types and clinical features, also to invest the distribution of patients with positive expression of HER-2 gene. Methods：The expression of HER-2 gene in the 223 samples with colon can-cer was detected by immunochemical approach. The expression of HER-2 gene in colon cancer tissues and adjacent tissues and dif erent pathologic types was analyzed byχ2 test. The correlation between the expression of HER-2 gene and clinical features was analyzed by Spearman. Results：The number of positive expression of HER-2 gene in colon cancer tissues and adjacent tissues were 74 and 0 respectively, the dif erence has statistical significance. The number of papil ary or tubular adenocarcinoma was 182, among them, 60 cases were positive expression. The number of mucinous adenocarcinoma was 41, among them, 14 cases were positive expression. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, which has no statistical significance. However, the expression of HER-2/neu gene has correlation with metastasis of lymph node and Dukes stage, which has statistical significance. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The correlated coef icient index was 0.320 and 0.320 respectively. In the 74 patients with positive expression of HER-2 gene, 59.4%of them were 60-74 years old. And there was 97.3%of the patients without family history of adenocarcinoma. Conclusion：The expression of HER-2/neu gene in colon cancer tissues was higher than in adjacent tissues. The expression of HER-2/neu gene has no correlation with sex, age, the maximum diameter, general classification, degree of dif erentiation and depth of invasion, but has correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene was positive correlation with metastasis of lymph node and Dukes stage. The expression of HER-2/neu gene with age of 60-74 years old and without family history of adenocarcinoma was higher than other groups.

Expression and Significance of Cyclooxygenase 2 Gene in Lung Cancer

To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in cancerous tissues and paired adjacent non-cancerous tissues from 56 patients and benign lesions from 12 patients. Our results showed that expression of COX-2 gene was detected in a significantly greater proportion of cancerous tissues (60.7 %) than adjacent noncancerous tissues (10.7 %, P<0.01) and benign lesions (3/12, P<0.05). Expression of COX-2 gene was higher in adenocarcinoma than in squamous carcinoma (P<0.01). There was no significant relationship between COX-2 gene expression and patients' age, sex, histological type of tumors, differentiation degree and TNM stages (P>0.05). The up-regulation of COX-2 gene in lung cancer tissues especially in adenocarcinoma suggested that COX-2 may play a role in the lung carcinogenesis and COX-2 gene may serve as a potential therapeutic target in lung cancer.

EXPRESSION PATTERN OF LUNG CANCER RELATED GENES IN MALIGNANT TRANSFORMATION OF BEP2D

Objective: To detect the expression difference of 60 lung cancer associated genes in human bronchial epithelial malignant transformation cell model (BEP2D) induced by alpha-particles. Methods: 60 lung cancer associated genes were collected and micro-arrayed onto the microscope slides using Cartesian PixSys5500 cDNA Microarray machine. Total RNA from BEP2D cells and passage 20 (R15H-20), passage 35 (R15H-35) cells derived from BEP2D following 1.5 Gy alpha-particles was extracted and labeled by fluorescent dye. The labeled probe was then hybridized with the cDNA. Results: 40, 47, 20 genes were detected in BEP2D, R15H-20 and R15H-35 respectively. The expression level of tumor suppressor genes decreased greatly in the transformed R15H-35. Most oncogenes decreased slightly in R15H-20. Most growth factors expressed only in R15H-20. Conclusion: In human bronchial epithelial malignant transformed cell model generated by alpha-particles, the loss-function of tumor suppressor genes at initiation stage was dominant, some related oncogenes and growth factors promoted the malignant transformation.

Construction of recombinant type 5 adenovirus expressing human DBC2 gene in bladder cancer cells

Objective:The aim of the study was to construct recombinant type 5 adenovirus expressing the human DBC2(deleted in breast cancer 2) gene for in vitro and in vivo assay in human bladder cancer research.Methods:The human DBC2 gene was first subcloned into a shuttle plasmid pAdTrack-CMV.After recombining with pAdEasy-1 vector in BJ5183 cells,the new recombinant vector pAdEasy-DBC2-CMV was transfected into HEK-293 cells to produce adenovirus.The human bladder cancer cell line T24 was infected with DBC2-containing adenovirus particles.Both RNA and protein were collected from cells harvested at 72 h after infection.Real time quantitative PCR(qPCR) and Western blot were used to examine mRNA and protein levels.Fluorescence microscopy was utilized to observe the expression of reporter green fluorescence protein.Results:Electrophoresis showed there was a 2.2 kb size band produced from high fidelity PCR.Pac I digest of the final produced recombinant vector yielded band sizes of approximately 30 kb and 4.5 kb.After virus infection with the pAdEasy-DBC2-CMV vector,the T24 cell line was observed to highly express green fluorescence protein under a fluorescence microscope.qPCR and Western blot assay identified that the DBC2 gene was overexpressed at both the mRNA and protein levels in virus transfected cells.Conclusion:By using the pAdEasy adenovirus system,we successfully constructed an adenovirus that could highly overexpress the tumor suppressor DBC2 gene in a bladder cancer cell line.This viral construct would be widely used for our further research in gene functional assays and gene therapy in bladder cancer.

Detection of TMPRSS2：ERG fusion gene in circulating prostate cancer cells

Aim： To investigate the existence of TMPRSS2：ERG fusion gene in circulating tumor cells （CTC） from prostate cancer patients and its potential in monitoring tumor metastasis. Methods- We analyzed the frequency of TMPRSS2： ERG and TMPRSS2：ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2：ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction （RT-PCR）. Fluorescence in situ hybridization （FISH） was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2：ERG fusion in 10 of the 15 CTC samples. Results： TMPRSS2： ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2：ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2：ERG fusion at the primary site. However, TMPRSS2：ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion： Although further study is required to address the association between TMPRSS2：ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.

Correlation research of Runt-related transcription factor 2 with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions

Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Background: Knowledge of HER2/Neu and BRCA1 Genes might be helpful for development of strategies for decreasing the burden of risk of breast cancer. Therefore, the aim of this study to detect the role of HER2/Neu and BRCA1 Genes expression in diagnosis of breast cancer in Sudanese women. Methodology: A total of 100 tissue samples obtained from patients with breast cancer in addition to 50 tissue samples obtained from patients with benign breast lesions, were detected the expression of HER2/Neu and BRCA1 Genes by Polymerase Chain Reaction (PCR). Results: The prevalence of HER2/Neu and BRCA1 Genes, among cases was 6%, and 10% respectively. Conclusion: HER2/Neu and BRCA1 Genes have a considerable contribution to etiology of breast cancer in Sudan that requires further consideration.

Correlation of Kif2a and HPK1 expression in breast cancer with the oncogene and drug resistance gene expression

Objective: To investigate the correlation of Kif2a and HPK1 expression in breast cancer with the oncogene and drug resistance gene expression. Methods: A total of 91 patients with breast cancer and 85 patients with breast adenoma who accepted surgical treatment in our hospital between August 2016 and February 2018 were selected, and the breast cancer tissues and breast adenoma tissues were collected respectively as the research samples. Fluorescence quantitative PCR method was used to detect the expression of Kif2a and HPK1 genes as well as oncogenes and drug resistance genes in sample tissues, and Pearson test was used to evaluate the inner link of Kif2a and HPK1 gene expression in breast cancer tissue with oncogene and drug resistance gene expression. Results: Kif2a mRNA expression in breast cancer tissues was higher than that in breast adenoma tissues whereas HPK1 mRNA expression was lower than that in breast adenoma tissues;oncogenes DEK, iASPP-SV, Stat3, MDM2 and Fra-1 mRNA expression were higher than those in breast adenoma tissues;drug resistance genes ESR1, MDR1, P-gp, MRP1 and GST- mRNA expression were higher than those in breast adenoma tissues whereas BCRP mRNA expression was lower than that in breast adenoma tissues. Correlation analysis showed that the Kif2a and HPK1 gene expression in breast cancer tissues were directly correlated with the expression of oncogenes and drug resistance genes. Conclusion: Kif2a gene is abnormally highly expressed whereas HPK1 gene is abnormally lowly expressed in breast cancer tissues, and they are involved in the regulation of oncogene and drug resistance gene expression.

乳腺癌组织中C-erbB-2、nm23基因的表达及其预后的关系

目的探讨乳腺癌组织中C-erbB-2基因和nm23基因的表达与预后的关系。方法采用免疫组织化学S-P法检测298例乳腺癌C-erbB-2、nm23基因表达情况并与乳腺癌病理类型、发病年龄、临床分期、腋淋巴结转移情况及5a生存率之间的关系进行分析。结果C-erbB-2基因阳性率36.24%(108/298),nm23基因阳性率为58.05%(173/298);C-erbB-2和nm23基因的表达与肿瘤病理类型、发病年龄、临床分期无明显相关性(P>0.05);C-erbB-2基因表达与腋淋巴结转移呈正相关,与5a生存率呈负相关,nm23基因的表达与腋淋巴结转移呈负相关,与5a生存率呈正相关(P<0.05);C-erbB-2基因表达与nm23基因表达两者之间明显负相关(P<0.05)。结论联合检测乳腺癌组织中C-erbB-2和nm23基因表达可能成为预测、评估乳腺癌患者临床预后的标记物。

C-erbB2基因shRNA表达质粒对结肠癌细胞生物学行为的影响

目的:观察C-erbB2基因shRNA表达质粒对结肠癌HT-29细胞生长抑制、细胞周期和凋亡的影响。方法:用MTT法及流式细胞仪分别检测pGenesil-erbB2实验组(PEG)、转染试剂对照组(TRCG)、阴性质粒对照组(NPCG)细胞对结肠癌细胞生长曲线、细胞周期及细胞凋亡率的影响。结果:pGenesil-erbB2实验组、转染试剂对照组、阴性质粒对照组的生长抑制率分别为39.65%、7.23%、8.05%,实验组明显高于其他两组(P<0.01);pGenesil-erbB2实验组、转染试剂对照组、阴性质粒对照组的G0/G1期细胞分别占74.93%、67.19%、68.05%,实验组明显高于其他两组(P<0.05);S期细胞分别占7.81%、14.02%、13.70%,实验组明显低于其他两组(P<0.05);pGenesil-erbB2实验组、转染试剂对照组、阴性质粒对照组的凋亡率分别为19.21%、3.13%、4.08%,实验组明显高于其他两组(P<0.01)。结论:C-erbB2基因siRNA重组质粒可以明显抑制结肠癌细胞的生长;可以将细胞周期阻滞于G0/G1期;可以明显增加结肠癌细胞的发生凋亡;说明C-erbB2基因在结肠癌的发生和发展中也起到非常重要的作用。

c-erbB-2、ER、PR在乳腺癌中的表达及其临床意义

目的探讨c-erbB-2、雌激素受体(ER)、孕激素受体(PR)在乳腺癌中的表达及其临床意义。方法采用免疫组化方法检测54例乳腺癌患者中c-erbB-2、ER、PR的表达,并分析其与临床的关系。结果54例乳腺癌中,ER、PR、c-erbB-2的阳性表达率分别为48.2%(26/54)、53.7%(29/54)、72.2%(39/54)。ER、PR的阳性表达率与患者年龄、有无淋巴结转移及组织学类型的差异无统计学意义(P>0.05);c-erbB-2阳性表达率与有无淋巴结转移的差异有统计学意义(P<0.05),与患者年龄、肿瘤体积及组织学类型的差异无统计学意义(P>0.05);ER、PR与c-erbB-2表达一致率为46.3%(25/54),表达不一致率为27.8%(15/54),ER、PR表达与c-erbB-2表达无显著相关性(P>0.05)。结论c-erbB-2的阳性表达是乳腺癌患者预后差的指标,联合检测ER、PR更有助于乳腺癌患者临床疗效和预后的判断。

Detection of Serum Aberrant CDKN2/P16 DNA in Colorectal Cancer

Objective： To search for a biomarker for colorectal cancer. Methods： The MSP, SSCP and deletion tests with serum have been taken simultaneously in 100 cases of colorectal cancer and 2 groups of controls, as well as the specimens of 26 cancer tissues and 22 paracancerous tissues and 29 cases of benign disease tissues for a contrast. Results： The aberrant methylation rate of P16 in the serum was 69.00%, deletion rate 4.00% and suspicious point mutation rate 15.00% in colorectal cancer patients. The data of cancer tissues were the same as those of the serum, but in paracancerous tissue those were significantly lower. In 10 cases, sequencing analysis revealed that there were 3 cases of missense, one case of frameshift and one case of nonsense. Among them, four cases had P16 protein deletion. As a tumor marker, the sensitivity of combined use of three methods was 88.00%, specificity 96.87% and accuracy 90.15%. The combined use of MSP and SSCP could obtain the same results. Conclusion： The content of DNA in serum is minimal, but it reflects the tumor burden of patients. The 10^-3 fragments of DNA could be detected in the serum by MSP. It can be used in the clinical diagnosis or popular investigation, and long-term postoperative follow-up.

乳腺癌中c-erbB-2与HIF-1基因表达相关性研究

目的探讨c-erbB-2与HIF 1基因过表达在乳腺癌进程中的内在相关性,寻找检测癌浸润转移的联合分子指标。方法乳腺癌组织芯片中200例样品经原位杂交检测c-erbB-2和HIF-1 mRNA表达,87例样本经荧光原位杂交检测c-erbB-2基因扩增。结果①185例乳腺癌样本中c-erbB-2和HIF 1基因有不同程度的共表达,浸润型的非特殊导管癌I级中c-erbB-2与HIF-1的表达2级以上的样本比率都超过70%。非特殊导管癌Ⅰ、Ⅱ级中c-erbB-2表达的样本比率高于HIF-1。c-erbB-2和HIF 1基因在非特殊导管癌Ⅰ、Ⅱ级中两者表达存在显著差异(P=0.003,P=0.036),小叶癌中两者表达无显著差异(P=0.607)。②浸润型的非特殊性导管癌Ⅰ级中c-erbB-2基因扩增与表达存在显著差异(P=0.046),非特殊性导管癌Ⅱ级与小叶癌中差异不显著(P=0.496m,P=0.878)。结论在乳腺癌浸润转移程度高时,c-erbB-2与HIF-1 mRNA的过表达一致,c-erbB-2扩增与其过表达一致,两者可成为乳腺癌浸润转移的联合分子指标。

乳腺癌超声造影特征与C-erbB-2、p53表达的相关性研究

目的 探讨乳腺癌肿块超声造影灌注特征与癌基因C-erbB-2、p53表达的相关性。方法 回顾性分析51例经手术及病理确诊的乳腺癌患者术前超声造影资料,术后对肿瘤标本采用免疫组织学方法测定C-erbB-2、p53蛋白表达情况,并分析其与超声造影特点之间的关系。结果 ①乳腺癌患者肿块C-erbB-2、p53阳性表达率分别为45.1%(23/51)和41.2%(21/51)。②51例乳腺癌患者肿块的增强模式均以向心性、快速增强、高增强为主,与C-erbB-2及p53表达无关。③C-erbB-2、p53阳性表达的乳腺癌患者,肿块均出现灌注不均匀的几率增加,两者间有关联(P<0.05),且C-erbB-2阳性表达的乳腺癌患者肿块出现灌注缺损的几率增加,与阴性表达的乳腺癌患者肿块比较差异有统计学意义(P<0.05)。④C-erbB-2、p53阳性表达的乳腺癌患者,肿块出现放射状或穿支血管的几率增加,两者间有关联(P<0.05),尤其以后者较为显著(P<0.01)。结论 乳腺癌超声造影特征与C-erbB-2、p53阳性表达之间存在一定的相关性。乳腺癌超声造影特征能在一定程度上反映癌细胞的生物学行为及预后,可为临床选择合理的治疗方案提供参考。