ABSTRACT
@# Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients, who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNAin colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance. The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNAexpression of KDR.
ABSTRACT
@# Objective: To investigate the effect of VEGFR2 gene polymorphism V297I on the clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with bevacizumab combining with chemotherapy. Methods:Atotal of 135 patients with advanced NSCLC, who were treated by bevacizumab plus platinum-based chemotherapy for first-line regimen, were included in this study. PCR-RFLP assay was used to detect the VEGFR2 genotypes in peripheral blood of patients and qPCR was used to detect the VEGFR2 mRNA in the cancer tissues of NSCLC patients. Logistic regression analysis was used to analyze the correlation between gene polymorphism and other variants, Kaplan-Meier assay to analyze the correlation between genotype and prognosis, and Cox regression model to analyze the risk factors for patients’PFS. Results: Of the polymorphisms analyzed, only polymorphism V297I was found to be of clinical significance. V297I locates in the coding region of VEGFR2, and it’s prevalence in the study population was as follows: CC genotype in 99 cases (73.33%), CT genotype in 33 cases (24.44%) and TT genotype in 3 cases (2.23%); the frequency of minor allele was 0.14, and the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P>0.05). The overall objective remission rate (ORR) of the 135 patients was 45.93%, the median progression free survival (mPFS) was 8.2 months and the median overall survival (mOS) was 20.8 months. The ORR, mPFS and mOS of patients with CT/TT genotype and CC genotype were 41.67%, 6.2 months, 18.9 months and 47.47%, 8.9 months and 21.5 months, respectively (all P<0.05).Additionally, the mRNAexpression of VEGFR2 in cancer tissues of the patients with CT/TT genotype was significantly higher than those with CC genotype (P< 0.01). The risk factors for patients’PFS included V297I, gender and ECOG score. Conclusion:Among advanced NSCLC patients treated by bevacizumab plus platinum-based chemotherapy, the polymorphism V297I of VEGFR2 may impact the clinical outcomes and prognosis of NSCLC patients treated with bevacizumab first line treatment by influencing the mRNAexpression of VEGFR2.
ABSTRACT
@#[Abstract] Objective: To investigate the relationship between expression of MICA/B (MHC class I chain-related proteinA/B) and disease-free survival (DFS) of patients with HER2+(human epidermal growth factor receptor 2) breast cancer tissue. Methods: Twenty six cases of corresponding para-cancerous tissue and 100 cases of HER2+ breast cancer tissue that preserved in wax at Zhengzhou People’ s Hospital Affiliated to Southern Medical University from January 2009 to June 2010 were collected for this study. Expression of MICA/ B in these tissue samples was detected by immunohistochemistry; and the relationship between MICA/B expression with clinicopathologic features as well as DFS was analyzed with Kaplan-Meier survival curve. Results: The expression of MICA/B in adjacent paracancerous tissues was negative (0/26), however, it was highly positive in cancer tissues (92/100), and the percentage with high expression was 65%(65/100), the difference was significant (P<0.05). High MICA/B expression rate in stage I was significantly higher than that in stage Ⅱ-Ⅲ (77.55% vs 52.94%， P<0.05), and the high expression rate in stage T1 was also significantly higher than that in stage T2-T4 (75.00% vs 52.27%， P<0.05). High MICA/B expression rate in ER+, PR+ group (with positive number≥1%) was significantly lower than that in ER- , PR-group (ER： 52.38% vs 74.14%，PR： 51.35% vs 73.02%， all P<0.05). MICA/B expression was correlated with clinical stages, the expression of ER, PR and tumor size (all P<0.05), but not associated with menopausal status, histological grade and lymph node metastasis (all P>0.05). Over-expression of MICA/B was closely associated with much better 6-year DFS rate in patients no matter with or without targeted therapy (the targeted group: 90.6% vs 72.2%; the untargeted group: 78.4% vs 58.8%, all P<0.05). Conclusion: Over-expression of MICA/B in HER2+ breast cancer tissue is closely related to DFS, which may be served as a potential prognosis indicator for patients with HER2+ breast cancer.
ABSTRACT
Objective:To investigate the effects of Fructus Corni extract on the B7-H6 expression in primary liver cancer cells of rats. Methods:Sixty SD rats were randomly divided into three groups, namely, model, matrine, and Cornus officinalis. The rat model bear-ing the primary liver cancer was induced by diethylnitrosamine, except for the rats in the control group. The rats in both the matrine and Cornus officinalis groups were fed with matrine and Cornus officinalis. The rats in model groups were fed with 0.9％sodium chlo-ride solution. The number of hepatocellular carcinoma nodules was calculated, and the tumor growth inhibition rate was also calculat-ed. The pathological changes of hepatic tissues in rats of each group were observed by hematoxylin and eosin staining. The expression levels of B7-H6 in these three groups were determined by immunohistochemistry and Western blot. Results:The number of liver nod-ules of the matrine and Fructus Corni group rats was lower than that of the model group (P<0.05). The tumor inhibition rate of the Cor-nus group was significantly higher than that of the matrine group (P<0.05). The tumor growth inhibition rate of the Cornus officinalis group was significantly higher than that of the matrine group (P<0.05). Immunohistochemistry showed that the positive expression of B7-H6 in the Cornus officinalis group and the matrine group was significantly higher than that in the model group (P<0.05), and the positive expression of B7-H6 in the Cornus officinalis group was significantly higher than that in the matrine group (P<0.05). Similarly, the protein expression of B7-H6 in the Cornus officinalis and matrine groups was significantly higher than that in the model group (P<0.05) by Western blot, while the protein expression of B7-H6 in the Cornus officinalis group was significantly higher than that in the matrine group (P<0.05). Conclusion:Fructus Corni extract may inhibit the growth of hepatocellular carcinoma through upregulating the B7-H6 expression.