ABSTRACT
【Objective】 To explore the differentially expressed genes in normal prostate and prostate cancer (PCa) tissues based on bioinformatics and screen out potential biomarkers for PCa, so as to provide scientific basis for later clinical medicine. 【Methods】 Three gene chip datasets of GSE55945, GSE46602 and GSE69223 were downloaded from GEO database, and differentially expressed genes (DEGs) were screened by the OmicStudio tools, and protein-protein interaction network (PPI) of DEGs was constructed by STRING. After Cytoscape was imported, CytoHubba plug-in was used to screen the top 30 genes in MCC score as key genes (Hub gene). DAVID was used for GO and KEGG enrichment analysis of Hub gene, and GraphPad Prism software was used to draw ROC curve. GEPIA database was used to verify the key genes, and survival analysis was further carried out. UALCAN was used to verify the correlation between the expression of key genes and Gleason grade of PCa. 【Results】 Three data sets (GSE55945, GSE46602 and GSE69223) obtained 428, 727 and 1285 differentially expressed genes, respectively. The Venn diagram shows that the three datasets contain 105 DEGs. Among 105 PPI networks corresponding to DEGs, the top 30 genes with MCC score were selected as Hub genes. The biological processes involved mainly include the positive regulation of protein kinase B signal, cell differentiation, positive regulation of transcription, negative regulation of transforming growth factor β receptor signaling pathway, positive regulation of cell migration, etc. The pathways involved are adhesion plaque, estrogen signaling pathway, etc. ROC curve results showed that the diagnostic ability of 9 genes in 3 data sets was statistically significant, and 9 Hub genes were CAV1, KDR, CAV2, TGFBR1, SLC7A11, GSTM2, GSTM3, GSTM5 and MYO6. Nine Hub genes were verified by GEPIA website, among which CAV1, KDR, CAV2, TGFBR1, GSTM2, GSTM3 and GSTM5 showed low expression in PCa, while SLC7A11 and MYO6 showed high expression in PCa. Survival analysis suggested that high GSTM5 expression prolonged OS in PCa patients. UALCAN results showed that the expression of GSTM5 gene was significantly correlated with Gleason grade, and the expression of GSTM5 gene decreased with the increase of Gleason score. 【Conclusion】 Hub genes CAV1, KDR, CAV2, TGFBR1, GSTM2, GSTM3 and GSTM5 are low expression in PCa, while SLC7A11 and MYO6 are high expression in PCa. GSTM5 gene is related to the survival rate of PCa. The expression of GSTM5 decreased with the increase of Gleason score, which indicated that GSTM5 may be a potential biomarker for PCa.
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Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.
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<p><b>OBJECTIVE</b>To evaluated HER2 status using immunohistochemistry (IHC) assay and fluorescence in situ hybridization (FISH) at two different time points of tissue fixation after surgical resection of gastric cancer, emphasizing the importance of standard operation and quality control in HER2 testing.</p><p><b>METHODS</b>Forty-one resection specimens of advanced gastric cancer were collected with tissue fixation periods of < 30 min or > 30 min after surgical resection. HER2 status was evaluated by immunohistochemistry (IHC) assay and fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>The frequency of HER2 expression by IHC in the samples with fixation time of < 30 min was higher than that in those of > 30 min (P < 0.05). However, no significant difference was observed by FISH (P > 0.05) between the two groups. Samples of < 30 min fixation time had high concordant results between IHC and FISH (100.0% for both positive and negative cases, Rho = 0.724, P < 0.05). In addition, HER2 expression by IHC was significantly correlated with Lauren classification, histologic differentiation, TNM stage and gender (P < 0.05).</p><p><b>CONCLUSION</b>The time to tissue fixation after surgical resection of more than 30 min has deleterious effect on the detection of HER2 by IHC although FISH testing is not affected.</p>