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鉴定 FAM83 家族成员在胰腺导管腺癌中的预后和治疗生物标志物。

Identification of Prognostic and Therapeutic Biomarkers among FAM83 Family Members for Pancreatic Ductal Adenocarcinoma.

机构信息

Department of General Surgery, Guangdong Provincial People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510080, China.

Shantou University of Medical College, Shantou 515000, China.

出版信息

Dis Markers. 2021 Mar 1;2021:6682697. doi: 10.1155/2021/6682697. eCollection 2021.

Abstract

Family with sequence similarity 83 (FAM83) members were shown recently to have oncogenic effect in a variety of cancer types, but the biological roles and prognostic value of FAM83 family in pancreatic ductal adenocarcinoma remain unknown. In the current study, the clinical significance and molecular function of the FAM83 family were assessed by multiple bioinformatics analysis. Besides, potential associations between differentially expressed genes (DEGs) of FAM83 family and antitumor immunity were evaluated using TIMER and TISIDB analyses. As the results show, FAM83A, FAM83D, FAM83E, and FAM83H were significantly upregulated in PDAC and were identified as DEGs. Higher expression of FAM83A, FAM83B, FAM83D, FAM83E, and FAM83H were associated with advanced tumor stage or worse patient prognosis. Importantly, the overexpression of DEGs was found to be significantly correlated with activated KRAS and loss of SMAD4, which are important drivers for PDAC. Further, FAM83A, FAM83D, and FAM83H were associated with CD8 T cell, Gamma Delta T cell, and CD4 T cell infiltration in PDAC and FAM83H was found closely correlated with some immunomodulators including immunoinhibitors, immunostimulators, and MHC molecules. In conclusion, FAM83A, FAM83D, FAM83E, and FAM83H have significant prognostic value in PDAC and they may play important roles in regulating tumor progression and the immune cell infiltration.

摘要

最近的研究表明,家族与序列相似性 83(FAM83)成员在多种癌症类型中具有致癌作用,但 FAM83 家族在胰腺导管腺癌中的生物学作用和预后价值仍不清楚。在本研究中,通过多种生物信息学分析评估了 FAM83 家族的临床意义和分子功能。此外,还使用 TIMER 和 TISIDB 分析评估了 FAM83 家族差异表达基因(DEGs)与抗肿瘤免疫之间的潜在关联。结果表明,FAM83A、FAM83D、FAM83E 和 FAM83H 在 PDAC 中显著上调,并被鉴定为 DEGs。FAM83A、FAM83B、FAM83D、FAM83E 和 FAM83H 的高表达与肿瘤晚期或患者预后不良相关。重要的是,发现 DEGs 的过表达与激活的 KRAS 和 SMAD4 的缺失显著相关,这是 PDAC 的重要驱动因素。此外,FAM83A、FAM83D 和 FAM83H 与 PDAC 中的 CD8 T 细胞、Gamma Delta T 细胞和 CD4 T 细胞浸润相关,并且发现 FAM83H 与包括免疫抑制剂、免疫刺激剂和 MHC 分子在内的一些免疫调节剂密切相关。总之,FAM83A、FAM83D、FAM83E 和 FAM83H 在 PDAC 中具有显著的预后价值,它们可能在调节肿瘤进展和免疫细胞浸润方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9641/7943308/2c2961c5908d/DM2021-6682697.001.jpg

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