Macrophages Phenotype Regulated by IL-6 Are Associated with the Prognosis of Platinum-Resistant Serous Ovarian Cancer: Integrated Analysis of Clinical Trial and Omics

Abstract

Background. The treatment of platinum-resistant recurrent ovarian cancer (PROC) is a clinical challenge and a hot topic. Tumor microenvironment (TME) as a key factor promoting ovarian cancer progression. Macrophage is a component of TME, and it has been reported that macrophage phenotype is related to the development of PROC. However, the mechanism underlying macrophage polarization and whether macrophage phenotype can be used as a prognostic indicator of PROC remains unclear. Methods. We used ESTIMATE to calculate the number of immune and stromal components in high-grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas database. The differential expression genes (DEGs) were analyzed via protein–protein interaction network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to reveal major pathways of DEGs. CD80 was selected for survival analysis. IL-6 was selected for gene set enrichment analysis (GSEA). A subsequent cohort study was performed to confirm the correlation of IL-6 expression with macrophage phenotype in peripheral blood and to explore the clinical utility of macrophage phenotype for the prognosis of PROC patients. Results. A total of 993 intersecting genes were identified as candidates for further survival analysis. Further analysis revealed that CD80 expression was positively correlated with the survival of HGSOC patients. The results of GO and KEGG analysis suggested that macrophage polarization could be regulated via chemokine pathway and cytokine–cytokine receptor interaction. GSEA showed that the genes were mainly enriched in IL-6-STAT-3. Correlation analysis for the proportion of tumor infiltration macrophages revealed that M2 was correlated with IL-6. The results of a cohort study demonstrated that the regulation of macrophage phenotype by IL-6 is bidirectional. The high M1% was a protective factor for progression-free survival. Conclusion. Thus, the macrophage phenotype is a prognostic indicator in PROC patients, possibly via a hyperactive IL-6-related pathway, providing an additional clue for the therapeutic intervention of PROC.

Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM

“…For instance, elevated levels of oxidative stress may precipitate apoptosis or impair functionality in immune cells, thereby diminishing the efficacy of immune infiltration ( 60 – 62 ). Moreover, oxidative stress may facilitate the proliferation and functional enhancement of immune suppressive cells within the tumor microenvironment, such as TAMs, further inhibiting the immune cells’ action against tumors ( 63 , 64 ). Currently, immunotherapy is recognized as an effective treatment strategy for various cancers ( 65 ).…”

Unraveling the role of disulfidptosis-related LncRNAs in colon cancer: a prognostic indicator for immunotherapy response, chemotherapy sensitivity, and insights into cell death mechanisms

“…The tumor microenvironment (TME) encompasses the contextual milieu surrounding tumor cells, comprising diverse constituents including blood vessels, immune cells, fibroblasts, and stroma. These elements engage in dynamic interactions, wherein the equilibrium between the immune system and the tumor intricately modulates this dynamic interplay ( Bruschini et al, 2021 ; Wu et al, 2023 ). Comprehending immune cell infiltration within the TME holds pivotal significance in elucidating tumor immune evasion mechanisms and facilitating insights into tailored therapeutic approaches.…”

“…Comprehending immune cell infiltration within the TME holds pivotal significance in elucidating tumor immune evasion mechanisms and facilitating insights into tailored therapeutic approaches. Enhanced understanding of immune infiltration in the tumor microenvironment can optimize treatment protocols, ultimately yielding improved clinical outcomes ( Wu et al, 2023 ; Yang et al, 2023 ). Understanding the immune cell infiltration within the TME is crucial for comprehending the immune evasion mechanisms of tumors and providing insights into personalized treatment strategies.…”

Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures

“…In order to conduct a more in-depth analysis of the data, specifically regarding the makeup of immune cells, the CIBERSORT algorithm was utilized, with outcomes deemed statistically significant if the p-value was below 0.05. R software (version 4.1.1) was utilized for all statistical analyses, incorporating specific R packages like ‘survival’ for Kaplan-Meier analysis and ‘ggplot2’ for data visualization [ 22 ]. A significance level of 0.05 was used to determine statistical significance based on two-sided p-values.…”