Pan‐cancer analysis of immune complement signature c3/c5/c3ar1/c5ar1 in association with tumor immune evasion and therapy resistance

Bashir Lawal, Sung Hui Tseng, Janet Olayemi Olugbodi, Sitthichai Iamsaard, Omotayo B. Ilesanmi, Mohamed H. Mahmoud, Sahar H. Ahmed, Gaber El Saber Batiha, Alexander T.H. Wu

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2 引文 斯高帕斯(Scopus)

摘要

Despite the advances in our understanding of the genetic and immunological basis of cancer, cancer remains a major public health burden with an ever‐increasing incidence rate globally. Nevertheless, increasing evidence suggests that the components of the complement system could regulate the tumor microenvironment (TME) to promote cancer progression, recurrence, and metastasis. In the present study, we used an integrative multi‐omics analysis of clinical data to explore the relationships between the expression levels of and genetic and epigenetic alterations in C3, C5, C3AR1, and C5AR1 and tumor immune evasion, therapy response, and patient prognosis in various cancer types. We found that the complements C3, C5, C3AR1, and C5AR1 have deregulated expression in human malignancies and are associated with activation of immune‐related oncogenic processes and poor prognosis of cancer patients. Furthermore, we found that the increased expression levels of C3, C5, C3AR1, and C5AR1 were primarily predicted by copy number variation and gene methylation and were associated with dysfunctional T‐cell phenotypes. Single nucleotide variation in the gene signature co‐occurred with multiple oncogenic mutations and is associated with the progression of onco‐immune‐related diseases. Further correlation analysis revealed that C3, C5, C3AR1, and C5AR1 were associated with tumor immune evasion via dysfunctional T‐cell pheno-types with a lesser contribution of T‐cell exclusion. Lastly, we also demonstrated that the expression levels of C3, C5, C3AR1, and C5AR1 were associated with context‐dependent chemotherapy, lym-phocyte‐mediated tumor killing, and immunotherapy outcomes in different cancer types. In conclusion, the complement components C3, C5, C3AR1, and C5AR1 serve as attractive targets for strategizing cancer immunotherapy and response follow‐up.
原文英語
文章編號4124
期刊Cancers
13
發行號16
DOIs
出版狀態已發佈 - 8月 2 2021

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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