FAM83H overexpression predicts worse prognosis and correlates with less CD8 + T cells infiltration and Ras-PI3K-Akt-mTOR
- PDF / 2,355,841 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 33 Downloads / 161 Views
RESEARCH ARTICLE
FAM83H overexpression predicts worse prognosis and correlates with less CD8+ T cells infiltration and Ras‑PI3K‑Akt‑mTOR signaling pathway in pancreatic cancer H. Zhuang1,2 · C. Zhang2 · B. Hou2 Received: 19 March 2020 / Accepted: 28 April 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract Background Family with sequence similarity 83 members H (FAM83H) is one member of Family with sequence similarity 83 (FAM83) family, which possess oncogenic properties in several types of cancer. However, the potential function of FAM83H in pancreatic cancer (PC) still remain unknown. Aim This study aims to explore the role of FAM83H during pancreatic carcinogenesis and the regulation of immune infiltration in PC. Methods In the current study, the clinical significance and potential biological of FAM83H were evaluated by bioinformatics analysis. Possible associations between FAM83H expression and tumor immunity were analyzed using ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA). Results FAM83H expression was significantly upregulated in tumor tissues, and positively associated with higher histologic grade, tumor recurrence, and worse prognosis. FAM83H overexpression is notably associated with KRAS activation. And functional enrichment analysis demonstrated that FAM83H may be involved in positive regulation of cell proliferation and migration, Ras protein signal transduction, regulation of cell–matrix adhesion, epithelial to mesenchymal transition (EMT), TGF-β receptor signaling in EMT, and activated NOTCH transmits signal to the nucleus. ESTIMATE algorithm and ssGSEA demonstrated that FAM83H overexpression suppressed the infiltration and antitumor activity of tumor-infiltrating lymphocytes (TILs), especially for CD8+ T cells. Besides, FAM83H overexpression significantly correlated with low expression of TIL-related gene markers (e.g. CD8A, CD8B, CD2, CD3D, and CD3E). Conclusion The study suggests that FAM83H overexpression predicts poor prognosis and correlates with less CD8+ T cells infiltration and Ras-PI3K-Akt-mTOR signaling pathway in PC. Keywords Pancreatic cancer · FAM83H · CD8+ T cells · RAS-PI3K-Akt-mTOR · TGF-β · NOTCH1
Introduction
* C. Zhang [email protected] * B. Hou [email protected] 1
Shantou University of Medical College, Shantou 515000, China
Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou 510080, China
2
Pancreatic cancer (PC) is one of the most aggressive malignancies, causing 4.5% of all cancer related deaths worldwide in 2015 [1]. Its 5-year survival is only about 8% [2]. And it is wildly considered as a highly immunosuppressive cancer [3]. Immune checkpoint inhibitors (ICIs) have been effectively used for several solid tumors, such as melanoma, nonsmall cell lung cancer, and hepatocellular carcinoma [4, 5]. However, these drugs fail to demonstrate efficacy in patients with PC due to the lack of CD8+ T cells in the TME
Data Loading...
