Analysis of expression and clinical significance of SHCBP1 gene in lung adenocarcinoma based on bioinformatics / 中国免疫学杂志

Objective:To analyze the expression and clinical significance of SHC SH2-binding protein 1(SHCBP1)in lung adenocarcinoma(LUAD).Methods:Oncomine,TIMER,UALCAN,GEPIA,Kaplan-Meier plotter and STRING databases were used to explore the effect of SHCBP1 on progression and immune infiltration of LUAD.Results:Expression of SHCBP1 mRNA in LUAD tissue was significantly higher than that in normal lung tissue(P<0.05).Expression of SHCBP1 mRNA was significantly increased in LUAD patients with smoking history,nodal metastasis,late clinical stage and TP53 mutation(P<0.05).Survival analysis by GEPIA and Kaplan-Meier plotter databases showed that LUAD patients with high SHCBP1 mRNA expression had a lower overall survival rate(P<0.05).SHCBP1 mRNA was correlated with immune cell infiltration,immune cell markers and immune checkpoint expression in LUAD.Conclusion:High expression of SHCBP1 is related to poor prognosis and tumor immune infiltration of LUAD patients.

TIM-3 gene is highly expressed in ephithelial ovarian cancer to promote proliferation and migration of ovarian cancer cells / 南方医科大学学报

OBJECTIVE@#To analyze the expression of immunoglobulin mucin molecule 3 (TIM-3) in epithelial ovarian cancer (EOC) and the effects of TIM-3 knockdown and overexpression on proliferation and migration of ovarian cancer cells.@*METHODS@#We analyzed TIM-3 expression in EOC and normal ovarian tissues using GEPIA database. We also detected TIM-3 expression levels in 82 surgical specimens of EOC and 18 specimens of normal ovarian tissues using immunohistochemistry, and analyzed the correlation of TIM-3 expression with clinicopathological parameters and survival outcomes of the patients. The expression of TIM-3 and Wnt1 mRNA in the tissues were detected using qRT-PCR. We constructed SKOV3 cell models of TIM-3 knockdown and overexpression and examined the changes in proliferation, apoptosis, migration and invasion of the cells using MTT assay, Annexin V-FITC/PI staining, scratch test and Transwell assay. The activity of Wnt/β-catenin pathway in the transfected was detected using dual luciferase reporter assay, and the mRNA levels of TCF-7, TCCFL-2 and CD44 were detected using qPCR. The protein expressions of MMP-9, CD44, Wnt1, β-catenin and E-cad in the transfected cells were detected with Western blotting.@*RESULTS@#The positive expression rate of TIM-3 was significantly higher in EOC tissues than in normal ovarian tissues (P < 0.05). The expression of TIM-3 was significantly correlated with FIGO stage, histological differentiation and lymph node metastasis, and was positively correlated with Wnt1 level (P < 0.05). In SKOV3 cells, TIM-3 knockdown significantly lowered the activity of Wnt/ β-catenin pathway, inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. TIM-3 knockdown significantly down-regulated the mRNA levels of TCF-7, TCFL-2 and CD44 and the protein levels of MMP-9, CD44, Wnt1 and β-catenin, and significantly up-regulated the expression level of E-cad (P < 0.05). Overexpression of TIM-3 caused opposite effects in SKOV3 cells.@*CONCLUSION@#TIM-3 is highly expressed in EOC tissue to promote malignant behaviors of the tumor cells possibly by activating the Wnt/β-catenin signal pathway.

Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction / 解剖学报

Objective To explore the abnormal expression of ubiquitin D (UBD) and glypican-3 (GPC3) among patients of hepatocellular carcinoma (HCC) by using analysis tools of genomics and epigenetics, so as to study their prognostic effects. Methods The online tools called ULCAN( http://ualan.path.uab.edu) and Gene Expression Profiling Interative Analysis (GEPIA) were used to perform expression analysis in genomics and epigenetics of UBD and GPC3. Moreover, GEPIA was conducted to evaluate the survival effects on HCC patients. The GeneCards was used to find the localization of UBD and GPC3 in tumor tissue and normal tissue. The STRING was utilized to perform the construction of PPI network and gene annotation. The correlation between UBD and GPC3 in progress of HCC was revealed based on Pearson correlation coefficient. Results UBD and GPC3 were dramatically up-regulated in HCC tissues, with downregulation of methylation level. UBD was located in 6p22. 1 with primary expression in the nucleus, while GPC3 was located in Xq26. 2 with main expression in the plasma membrane, extracellular matrix, endoplasmic reticulum, lysosome and golgi apparatus. The enrichment analysis showed that, UBD was enriched in activities involving proteasome, such as post-translation protein modification, ubiquitination and deubiquitination. GPC3 was enriched in the biosynthetic and catabolic process of glycosaminoglycan, possessed relationship with proteoglycans in cancer, ECM-receptor interaction, cell adhesion molecules (CAMs). Both of UBD and GPC3 were shown to exhibit a positive linear correlation, which suggested that GPC3 and UBD mediated the pathological process of HCC in cooperation. The survival analysis showed that, GPC3 exhibited a critical effect on survival of HCC patients. Conclusion UBD and GPC3 represent up-regulation in tumor tissue, in which GPC3 possesses a greater impact on the prognosis of HCC. GPC3 could be potential to serve as a practical biomarker for early diagnosis and medical intervention.

Expression and mechanism of TMEM45A in renal clear cell carcinoma / 实用肿瘤学杂志

Objective The objective of this study was to investigate the expression and function of TMEM45A( transmem-brane protein 45A)in clear cell renal cell carcinoma(ccRCC). Methods The data of TMEM45A in Oncomine database were extrac-ted by R language. The relationship between the expression level of TMEM45A and the stage or survival time of ccRCC was analyzed by GEPIA database. qRT-PCR and Western blot were used to detect the expression of TMEM45A in ccRCC tissues and renal cell carcinoma cell lines. After transfection of TMEM45A siRNA,the low expression ofTMEM45A in Caki-1 cells was confirmed by qRT-PCR and Western blot. Cell proliferation after knockdown TMEM45A was analyzed in Caki-1 cells by CCK8. The mechanism of action in the low expression of TMEM45A inhibited cell proliferation was analyzed in Caki-1 cells by qRT-PCR and Western blot. Results A total of 384 TMEM45A-related studies were collected in the Oncomine database,with 35 statistically significant differ-ences,25 of them elevated and 10 decreased. Four studies were associated with ccRCC with a total of 115 samples. The expression of TMEM45A was significantly increased in ccRCC(P<0. 05). It was also found that the high expression of TMEM45A was closely as-sociated with high ccRCC stage and poor prognosis( P<0. 05). When compared with the normal kidney tissues,TMEM45A mRNA was significantly increased in ccRCC tissues(P<0. 05). The expression of TMEM45A at levels of mRNA and protein in Caki-1 and 786-0 cells was higher than that in normal renal tubular epithelial HK-2 cells. After transfection with TMEM45A siRNA for 48h and 72h,the proliferation of Caki-1 cells was significantly decreased(P<0. 001). At the same time,it was found that the expression of PCNA and cyclin D1 at levels of mRNA and protein was significantly decreased ( P <0. 05). Conclusion The expression of TMEM45A is elevated in ccRCC and is associated with ccRCC staging and prognosis. It may be involved in the proliferation of renal carcinoma cells by regulating PCNA and Cyclin D1.