Dataset Information

Bioinformatics Analysis of Potential Therapeutic Targets and Prognostic Biomarkers amid CXC Chemokines in Ovarian Carcinoma Microenvironment.

ABSTRACT:

Background

Ovarian cancer (OC) is one of the leading lethal gynecologic cancers of women around the world. More than 70% of patients are diagnosed with stage III or IV with poor outcome. This is partly because of lacking early effective screening techniques and potential biomarkers of OC. CXC chemokines in tumor microenvironment (TME) and their interaction with relative receptors can excite the downstream signaling pathways to influence tumor progression. However, the role of CXC chemokines in OC has not been identified.

Methods

ONCOMINE, GEPIA, Kaplan-Meier plotter, cBioPortal, TIMER, Metascape, and LinkedOmics were applied in our study.

Results

The transcriptional levels of CXCL1/8/9/10/11/12/13/14/16/17 were significantly elevated while CXCL3 was obviously reduced in OC vs normal ovarian tissue. CXCL8/9/11/13 were correlated with clinic pathological stage. Patients with low expression of CXCL8/9/11/13 were associated with better prognosis. We also found that CXCL3 and CXC12 could be used as potential prognostic markers of OC through Kaplan-Meier plotter. Patients with high expression of CXCL3/12 had a significantly better prognosis. Their functions focus on locomotion, signaling, response to stimulus, undergoing the process of multiorganism, immune system, biological regulation, etc. The differentiated CXC chemokines mainly participate in cytokine-cytokine receptor interaction, chemokine signaling pathway, IL-17 signaling pathway, and toll-like receptor signaling pathway. Our results showed that CXC chemokines were highly correlated with infiltration of immune cells. The kinase targets of differentially expressed CXC chemokines are mainly in ATM, LYN, LCK, PLK1, FYN, CDK2, and ATR.

Conclusions

Our results may provide a new insight for selecting precision biomarkers of targeted therapy of OC.

SUBMITTER: Jin Y

PROVIDER: S-EPMC7964101 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Bioinformatics Analysis of Potential Therapeutic Targets and Prognostic Biomarkers amid CXC Chemokines in Ovarian Carcinoma Microenvironment.

Jin Yunfeng Y Lin Qiwang Q Fei He H Xue Lujie L Li Li L Xi Qinghua Q Jiang Hua H

Journal of oncology 20210128

<h4>Background</h4>Ovarian cancer (OC) is one of the leading lethal gynecologic cancers of women around the world. More than 70% of patients are diagnosed with stage III or IV with poor outcome. This is partly because of lacking early effective screening techniques and potential biomarkers of OC. CXC chemokines in tumor microenvironment (TME) and their interaction with relative receptors can excite the downstream signaling pathways to influence tumor progression. However, the role of CXC chemoki ...[more]

PMID: 33763130

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Project description:BackgroundSeveral studies have indicated that CXC chemokines influence the prognosis and therapy in patients with hepatocellular carcinoma (HCC). However, there are limited studies on the roles of CXC chemokines in HCC based on data acquired from various databases. This study aimed to conduct an in-depth and comprehensive bioinformatic analysis of the expression and functions of CXC chemokines in HCC.MethodsData was obtained from various databases including ONCOMINE, UALCAN, STRING, GeneMinia, DAVID, Kaplan-Meier plotter, TIMER, GSCALite and NetworkAnalyst for the analysis of the expression and functions of the CXC chemokines in HCC.ResultsAnalysis of the differential expression levels of CXC chemokines between HCC and adjacent normal tissues revealed that the mRNA expression levels of CXCL1/2/5/6/7/12/14 were significantly lower in HCC tissues than those in adjacent normal tissues, whereas the mRNA expression levels of CXCL9/16/17 were significantly higher in HCC tissues. Analysis of the relationship between CXC chemokines and overall survival revealed that high mRNA expression levels of CXCL1/3/5/6/8 were associated with poor overall survival, whereas high mRNA expression levels of CXCL2/4/7/9/10/12 were associated with better overall survival. The functions of CXC chemokines and related genes were associated with cytokine-cytokine receptor interactions and chemokine signaling pathway. Analysis of the association between CXC chemokines and activity of cancer pathways indicated that the DNA damage response and hormone androgen receptor (AR) signaling pathways were inhibited, whereas apoptosis, epithelial-mesenchymal transition (EMT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways were activated. The expression of CXC chemokines was positively correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells).ConclusionsThis study has demonstrated that CXC chemokines can influence survival of patients with HCC by recruiting different types of immune cells into the tumor microenvironment.

Project description:BackgroundPancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified.MethodsBioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer.ResultsExcept for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times.ConclusionsThese findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.

Dataset Information

Bioinformatics Analysis of Potential Therapeutic Targets and Prognostic Biomarkers amid CXC Chemokines in Ovarian Carcinoma Microenvironment.

Background

Methods

Results

Conclusions

Publications

Bioinformatics Analysis of Potential Therapeutic Targets and Prognostic Biomarkers amid CXC Chemokines in Ovarian Carcinoma Microenvironment.

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