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A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer.

ABSTRACT: Breast cancer (BC) is a major human health problem due to its increasing incidence and mortality rate. CC and CXC chemokines are associated with tumorigenesis and the progression of many cancers. Since the prognostic values of CC and CXC families' expression in various types of cancers are becoming increasingly evident, we aimed to conduct a comprehensive bioinformatics analysis elucidating the prognostic values of the CC and CXC families in BC. Therefore, TCGA, UALCAN, Kaplan-Meier plotter, bc-GenExMiner, cBioPortal, STRING, Enrichr, and TIMER were utilized for analysis. We found that high levels of CCL4/5/14/19/21/22 were associated with better OS and RFS, while elevated expression of CCL24 was correlated with shorter OS in BC patients. Also, high levels of CXCL9/13 indicated longer OS, and enhanced expression of CXCL12/14 was linked with better OS and RFS in BC patients. Meanwhile, increased transcription levels of CXCL8 were associated with worse OS and RFS in BC patients. In addition, our results showed that CCL5, CCL8, CCL14, CCL20, CCL27, CXCL4, and CXCL14 were notably correlated with the clinical outcomes of BC patients. Our findings provide a new point of view that may help the clinical application of CC and CXC chemokines as prognostic biomarkers in BC.

SUBMITTER: Hozhabri H

PROVIDER: S-EPMC9209453 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer.

Hozhabri Hossein H Moghaddam Marziyeh Mazaheri MM Moghaddam Madiheh Mazaheri MM Mohammadian Ali A

Scientific reports 20220620 1

Breast cancer (BC) is a major human health problem due to its increasing incidence and mortality rate. CC and CXC chemokines are associated with tumorigenesis and the progression of many cancers. Since the prognostic values of CC and CXC families' expression in various types of cancers are becoming increasingly evident, we aimed to conduct a comprehensive bioinformatics analysis elucidating the prognostic values of the CC and CXC families in BC. Therefore, TCGA, UALCAN, Kaplan-Meier plotter, bc- ...[more]

PMID: 35725915

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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.

Project description:Colon adenocarcinoma (COAD) is a prevalent and aggressive form of cancer that necessitates the identification of robust biomarkers for early diagnosis and treatment. Therefore, this project was launched to identify a few key biomarkers from CC and CXC chemokine families for the accurate detection of COAD. Hub gene identification was performed using CytoHubba analysis. Clinical samples from COAD patients and normal individuals were collected and subjected to appropriate methods for DNA and RNA extraction. The expression levels of hub genes were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), while promoter methylation analysis was conducted using targeted bisulfite sequencing (bisulfite-seq). Additionally, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized to validate the findings based on clinical samples. CXCL10 (C-X-C motif chemokine ligand 10), CXCL12 (C-X-C motif chemokine ligand 12), CXCL16 (C-X-C motif chemokine ligand 16), and CCL25 (CC motif chemokine ligand 25) were denoted as the key hubs among CC and CXC chemokine families. Through RT-qPCR analysis, it was found that CXCL10, CXCL12, and CXCL16 were significantly up-regulated, while CCL25 was down-regulated in COAD patients compared to healthy controls. Later on, these findings were also validated using TCGA and GEO datasets consisting of COAD and normal control samples. Furthermore, we investigated the promoter methylation status of these chemokine genes in COAD patients. Our results revealed significant dysregulation of promoter methylation, suggesting an epigenetic mechanism underlying the altered expression of CXCL10, CXCL12, CXCL16, and CCL25 in COAD. In addition to this, various additional aspects of the CCL25, CXCL10, CXCL12, and CXCL16 have also been uncovered in COAD during the present study. This study highlights the dysregulation of CXCL10, CXCL12, CXCL16, and CCL25 chemokine members in COAD patients, emphasizing their significance as potential biomarkers and therapeutic targets in the management of this deadly disease. However, further investigations are warranted to elucidate the underlying molecular mechanisms and evaluate the clinical utility of these findings.

Dataset Information

A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer.

Publications

A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among CC and CXC chemokines in breast cancer.

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