A bioinformatic analysis: the overexpression and clinical significance of FCGBP in ovarian cancer.
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ABSTRACT:
SUBMITTER: Wang K
PROVIDER: S-EPMC7993703 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle-Ottawa Scale (NOS) for quality assessment of case-control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma.
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Project description:Objective: Cyclooxygenase-2 (COX-2) is a critical enzyme associated with inflammation and tumorigenesis. Although several studies have compared the expression of COX-2 in endometrial cancer tissues and normal tissues, the results have been inconsistent thus far. This study aims to conduct a meta-analysis to elucidate the role of COX-2 in the determination of the risk, prognosis, and clinical features of endometrial cancer. Methods: We retrieved the suitable studies on the association between COX-2 expression and endometrial cancer from PubMed, EMBASE, and Web of Science databases that were published between 1999 and September 31st, 2019. The hazard ratio (HR) and 95% confidence intervals (CIs) were retrieved to assess the relationship between COX-2 expression and the prognosis of endometrial cancer. The odds ratio (OR) and 95% CIs were calculated to evaluate the correlation between COX-2 expression and the risk and clinical features of endometrial cancer. Results: To investigate the association between COX-2 expression and the susceptibility, clinical features, and prognosis of endometrial cancer, we performed a meta-analysis on data from selected studies that collectively involved 273 normal individuals and 1,376 patients with endometrial cancer. Overall, the pooled analysis indicated that COX-2 expression was significantly associated with susceptibility (Caucasians, OR = 3.94, 95% CI = 2.17-7.17, P < 0.05; Asians, OR = 20.51, 95% CI = 8.54-49.26, P < 0.05), cancer stage (OR = 3.01, 95% CI = 1.95-4.67, P < 0.05), myometrial invasion (OR = 1.59, 95% CI = 1.17-2.15, P < 0.05), lymph node metastasis (OR = 1.63, 95% CI = 1.18-2.26, P < 0.05), and prognosis (OR = 2.91, 95% CI = 1.17-4.66, P < 0.05) in endometrial cancer. Conclusions: Our findings suggested that COX-2 overexpression is significantly associated with poor prognosis and advanced clinical features in endometrial cancer. Therefore, COX-2 may function as an effective prognostic biomarker and a potential therapeutic target for endometrial cancer.
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Project description:ObjectiveSeveral studies have found that MMP-9, one of the extracellular matrix-degrading proteinases, was involved in EC's (endometrial cancer) clinical progression and prognosis. However, the results involving the associations of MMP-9 expression with risk, clinical features and prognosis of EC were conflicting. Therefore, we performed a systematic review and meta-analysis to clarify the correlation of MMP-9 expression with EC.MethodsRelative studies involving the associations between MMP-9 expression and EC were retrieved from PubMed, Embase, Web of Science and CNKI (China National Knowledge Infrastructure) electronic databases. OR (odds ratio) with 95% CI (confidence interval) was applied to evaluate the associations of MMP-9 expression with risk and clinical features of EC. Furthermore, we evaluated the role of MMP-9 expression in prognosis of EC using HR and 95% CI. The funnel plots and Begg test were used to assess the publication bias.ResultsA total of 28 eligible studies were acquired from Pubmed, Embase, Web of science and CNKI databases. We found MMP-9 overexpression was significantly associated with the risk of EC (OR = 11.02, 95% CI = 7.51-16.16, P < 0.05). In the meantime, MMP-9 overexpression was significantly associated with the tumor grade, FIGO stage, lymph node metastasis and myometrial invasion (Tumor grade: OR = 1.68, 95% CI = 1.09-2.58, P < 0.05; FIGO stage: OR = 3.25, 95% CI = 1.73-6.08, P < 0.05; Lymph node metastasis: OR = 2.98, 95% CI = 1.27-7.03, P < 0.05; Myometrial invasion: OR = 2.42, 95% CI = 1.42-4.12, P < 0.05) in Asians. In addition, the overall results showed that MMP-9 overexpression predicted a worse prognosis of EC (OR = 1.82, 95% CI = 1.01-2.62, P < 0.05).ConclusionsMMP-9 overexpression might be a potential predictor of poor clinical progression and prognosis of EC.
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Project description:Background and objectives: Ovarian cancer is one of the leading causes of death among women worldwide. Most newly diagnosed ovarian cancer patients are diagnosed in advanced stages of the disease. Despite various treatments, most patients with advanced stage ovarian cancer, including serous ovarian cancer (the most common subtype of ovarian cancer), experience recurrence, which is associated with extremely poor prognoses. In the present study, we aimed to identify core genes involved in ovarian cancer and their associated molecular mechanisms, as well as to investigate related clinicopathological implications in ovarian cancer. Materials and methods: Three gene expression cohorts (GSE14407, GSE36668, and GSE38666) were obtained from the Gene Expression Omnibus databases to explore potential therapeutic biomarkers for ovarian cancer. Nine up-regulated and six down-regulated genes were screened. Three publicly available gene expression datasets (GSE14407, GSE36668, and GSE38666) were analyzed. Results: A total of 14 differently expressed genes (DEGs) were identified, among which nine genes were upregulated (BIRC5, CDCA3, CENPF, KIF4A, NCAPG, RRM2, UBE2C, VEGFA, and NR2F6) and were found to be significantly enriched in cell cycle regulation by gene ontology analysis. Further protein-protein interaction network analysis revealed seven hub genes among these DEGs. Moreover, Kaplan-Meier survival analysis showed that a higher expression of CDCA3 and UBE2C was associated with poor overall patient survival regardless of tumor stage and a higher tumor histologic grade. Conclusion: Altogether, our study suggests that CDCA3 and UBE2C may be valuable biomarkers for predicting the outcome of patients with advanced serous ovarian cancer.
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Project description:BackgroundCurrently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood.MethodsComprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions.ResultsWe analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages.ConclusionRYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.
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Project description:Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.
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Project description:BACKGROUND: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. METHODS AND RESULTS: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CONCLUSION: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.
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Project description:Immune checkpoint blockade (ICB), mainly anti-CTLA-4 and anti-PD-1/PD-L1 therapy, has showed promising clinical benefits in the treatment of some cancer types; however, its application in ovarian cancer is still in the primary stage. Immunophenotyping can help us understand the clinical characteristics and immune status of cancer, and thus benefit immunotherapy and personalized therapy. In this study, we clustered 907 ovarian cancer patients into three immune molecular subtypes (IMMSs) based on 48 genes. Expression data were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering was used to identify IMMS. Clinical and immunological characteristics and gene expression patterns of different IMMS were compared, and associations between IMMS and tumor microenvironment immune types were explored. Three IMMSs with different clinical and immunological characteristics were identified, in which type I and II ovarian cancer patients were similar to each other. There were more serous and low-grade tumors in type I and II ovarian cancer. IMMS was associated with disease-free survival before and after adjusting for clinical characteristics and ICB-related genes. Among the differentially expressed genes identified in our study, about 90% (25/28) were highly expressed in type I and II ovarian cancer. Genes related to ICB (CTLA-4, PD-L1, and PD-L2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type I and II ovarian cancer. Patients with type I and II ovarian cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. In contrast, patients with type III ovarian cancer may be insensitive to these treatments and require new therapies.
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Project description:ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.
| S-EPMC2409772 | biostudies-other
Project description:ObjectivesHuman epidermal growth factor receptor-2 (HER2) and 3 (HER3) belong to the epidermal growth factor receptor (EGFR) family of transmembrane receptor tyrosine kinases. In this study, we assessed HER2/HER3 expression levels in specimens of epithelial ovarian cancer and determined their correlation with clinical features of ovarian cancer.MethodsTissue microarrays (TMAs) were prepared from paraffin blocks of 105 ovarian tumour samples. HER2, HER3, PI3K, Akt, p-Akt, mTOR, p-mTOR, S6, and p-S6 expression levels were investigated using immunohistochemistry (IHC). HER2 and HER3 amplifications were determined using in situ hybridization (ISH). The correlation between HER2/3 expression and disease outcome of the patients including surgical outcome, progression-free survival (PFS) and overall survival (OS) was analysed.ResultsHER2 positivity was 3.8% by IHC and 5.7% by ISH, whereas that of HER3 was 12.4% and 8.6%, respectively. HER2 status by either IHC or ISH was not related to PFS (p=0.128, 0.168, respectively) and OS (p=0.245, 0.164, respectively). However, the HER3 status determined using fluorescence ISH was associated with poor PFS (p=0.035 on log rank test), which was a significant risk factor even after adjusting other possible risk factors in multivariate analysis (hazard ratio=2.377 [1.18-7.49], p=0.021). Expressions of Akt, p-mTOR, and S6 were also related with poor progression (p=0.008, 0.049, 0.014, respectively).ConclusionHER3 is possibly an independent marker for poor prognosis in individuals with ovarian cancer, as the HER3 signalling pathway is distinct from that of HER2. The possibility of targeted therapy for patients with HER3 alteration in ovarian cancer should be evaluated.
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