Dataset Information

Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis.

ABSTRACT:

Background

Interleukin-17A is a proinflammatory cytokine that is produced by TH17 cells, and plays a dual role in tumor progression, infectious diseases, and autoimmune disorders. Interleukin-17A is induced during colorectal tumorigenesis and angiogenesis, although some studies have reported an anti-tumor effect as well. The aim of our study was to assess the prognostic role of interleukin-17A in colorectal cancer and determine the potential mechanisms.

Methods

The GEO database was searched using the keyword "colorectal cancer", and 10 datasets were identified that included interleukin-17A mRNA expression and survival data of several colorectal cancer patient cohorts. The patients were stratified into the interleukin-17Ahigh and interleukin-17Alow groups based on the median expression level.

Results

Higher interleukin-17A mRNA levels were associated with better overall survival rates and the early tumor stage, indicating a protective role of interleukin-17A in colorectal cancer. Furthermore, interleukin-17A mRNA expression also correlated positively with that of TNFS11, CCR6, and CCL20, indicating that the anti-tumor effect of interleukin-17A is likely mediated by enhancing tumor antigen presentation by dendritic cells and recruiting the activated tumor-specific CD8+ cytotoxic T lymphocytes. The IL-23 and STAT3 mRNA levels were also significantly higher in the interleukin-17Ahigh group, which points to an upstream regulatory role of IL-23/STAT3 axis. Finally, the immune checkpoints PDCD1 (PD-1) and CD274 (PDL-1) were also positively correlated with interleukin-17A mRNA expression, indicating that interleukin-17A is a promising predictor of the immunotherapeutic outcome of PD-1/PDL-1 blockade in colorectal cancer.

Conclusion

Interleukin-17A mRNA is a protective factor in colorectal cancer and a promising biomarker for assessing the prognosis and immunotherapeutic response.

SUBMITTER: Yang W

PROVIDER: S-EPMC9797711 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis.

Yang Wei W Chen Jiejing J Liang Hailiang H Wu Wei W

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 20221201 12

<h4>Background</h4>Interleukin-17A is a proinflammatory cytokine that is produced by TH17 cells, and plays a dual role in tumor progression, infectious diseases, and autoimmune disorders. Interleukin-17A is induced during colorectal tumorigenesis and angiogenesis, although some studies have reported an anti-tumor effect as well. The aim of our study was to assess the prognostic role of interleukin-17A in colorectal cancer and determine the potential mechanisms.<h4>Methods</h4>The GEO database wa ...[more]

PMID: 36098359

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Project description:BackgroundInterleukin-17 (IL-17) is a pro-inflammatory cytokine that plays a vital role in the promotion of tumorigenesis in various cancers, including colorectal cancer (CRC). Based on current evidence, IL-17 binds to interleukin-17 receptor A (IL-17RA); however, the role of IL-17RA has not been elucidated in previous studies on CRC. In this study, we explored the role of IL-17RA in human CRC tissues and the progression of CRC in humans and mice.MethodsThe expressions of IL-17RA and epithelial-mesenchymal transition (EMT)-related genes were examined in CRC cells and tissue samples by quantitative real-time polymerase chain reaction. The role of IL-17RA in pathogenesis and prognosis was evaluated using a Chi-squared test, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis in 133 CRC patients. A tumor-bearing mice model was executed to evaluate the role of IL-17RA in tumor growth, vascularity and population of infiltrating immune cells.ResultsIL-17RA expression was found to be significantly higher in CRC tissues than in adjacent normal tissues. The expression of IL-17RA in Stage IV patients was significantly higher than that in Stages I and II patients. Patients with high IL-17RA expression exhibited significantly worse overall and CRC-specific survival than those with low IL-17RA expression. Functional assessment suggested that the knockdown of IL-17RA expression distinctly suppressed cellular proliferation, migration, invasion, and EMT-related gene expression. In a tumor-bearing mouse model, decreased IL-17RA expression significantly repressed tumor growth and vascularity and reduced the population of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).ConclusionReduced IL-17RA expression also suppressed cellular proliferation, migration, and invasion, and the expression of EMT genes. Knockdown of IL-17RA inhibited tumor growth and vascularity and decreased the population of Tregs and MDSCs in mouse tumors. Overall, IL-17RA expression was identified to be independently associated with the prognosis of patients with CRC.

Project description:BackgroundIn mice, the cytokine interleukin (IL)-17A causes a local accumulation of neutrophils within the bronchoalveolar space. IL-17A may thereby also contribute to an increased local proteolytic burden. In the current study, we determined whether mRNA for IL-17A is elevated and protein expression of IL-17A occurs locally in inflammatory cells within the human bronchoalveolar space during severe inflammation caused by organic dust. We also assessed the expression of the elastinolytic protease MMP-9 in this airway compartment.MethodsSix healthy, non-smoking human volunteers were exposed to organic dust in a swine confinement, a potent stimulus of neutrophil accumulation within the human bronchoalveolar space. Bronchoalveolar lavage (BAL) fluid was harvested 2 weeks before and 24 hours after the exposure and total and differential counts were conducted for inflammatory BAL cells. Messenger RNA for IL-17A was measured using reverse transcript polymerase chain reaction-enzyme linked immunoassay (RT-PCR-ELISA). Intracellular immunoreactivity (IR) for IL-17A and MMP-9, respectively, was determined in BAL cells.ResultsThe exposure to organic dust caused more than a forty-fold increase of mRNA for IL-17A in BAL cells. IL-17A immunoreactivity was detected mainly in BAL lymphocytes, and the number of these IL-17A expressing lymphocytes displayed an eight-fold increase, even though not statistically significant. The increase in IL-17A mRNA was associated with a substantial increase of the number of BAL neutrophils expressing MMP-9 immunoreactivity.ConclusionExposure to organic dust increases local IL-17A mRNA and because there is intracellular expression in BAL lymphocytes, this suggests that IL-17A protein can originate from lymphocytes within the human bronchoalveolar space. The fact that the increased IL-17A mRNA is associated with an increased number of MMP-9-expressing neutrophils is compatible with IL-17A increasing the local proteolytic burden through its neutrophil-accumulating effect.

Project description:BackgroundHeat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily.MethodsOnline analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher's exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan-Meier analysis and Cox's proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson's correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes.ResultsColorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan-Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113-3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair.ConclusionsOur results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.

Dataset Information

Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis.

Background

Methods

Results

Conclusion

Publications

Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis.

Similar Datasets

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