FAM83A 通过 ERK 信号通路驱动 PD-L1 的表达，并且 FAM83A/PD-L1 的共表达与肺腺癌的不良预后相关。
FAM83A drives PD-L1 expression via ERK signaling and FAM83A/PD-L1 co-expression correlates with poor prognosis in lung adenocarcinoma.
机构信息
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
出版信息
Int J Clin Oncol. 2020 Sep;25(9):1612-1623. doi: 10.1007/s10147-020-01696-9. Epub 2020 May 19.
PURPOSE
The purpose of this research was to explore the correlation and prognostic significance of FAM83A and programmed cell death-ligand 1 (PD-L1) protein expression in patients with lung adenocarcinoma (LUAD).
METHODS
A total of 130 LUAD specimens and 50 normal lung tissue specimens were analyzed for both FAM83A and PD-L1 expression by immunohistochemistry (IHC) analysis. The effect of FAM83A on PD-L1 and ERK pathway was evaluated by RT-PCR and western blot in vitro.
RESULTS
Both FAM83A and PD-L1 were upregulated in patients with LUAD and co-expression of them was significantly associated with tumor stage, metastasis and worse survival in LUAD. Multivariate cox regression analysis revealed that co-expression of FAM83A and PD-L1 was an independent prognostic factor impacting survival. Moreover, experiments in vitro showed FAM83A could promote the expression of PD-L1 through the ERK pathway.
CONCLUSION
FAM83A and PD-L1 may be potential therapeutic targets for LUAD. Co-expression of FAM83A and PD-L1 in tumor cells was a credible biomarker predictor for worse survival in resected cases. FAM83A may promote the expression of PD-L1 through ERK signaling pathway, thus causing immune escape of tumor.
目的
本研究旨在探讨肺腺癌（LUAD）患者中 FAM83A 与程序性死亡配体 1（PD-L1）蛋白表达的相关性及其预后意义。
方法
采用免疫组织化学（IHC）分析方法检测 130 例 LUAD 标本和 50 例正常肺组织标本中 FAM83A 和 PD-L1 的表达情况。通过 RT-PCR 和 Western blot 体外评估 FAM83A 对 PD-L1 和 ERK 通路的影响。
结果
FAM83A 和 PD-L1 在 LUAD 患者中均上调，且两者共表达与肿瘤分期、转移和 LUAD 患者的生存预后较差显著相关。多因素 Cox 回归分析显示，FAM83A 和 PD-L1 的共表达是影响生存的独立预后因素。此外，体外实验表明 FAM83A 可通过 ERK 通路促进 PD-L1 的表达。
结论
FAM83A 和 PD-L1 可能是 LUAD 的潜在治疗靶点。肿瘤细胞中 FAM83A 和 PD-L1 的共表达是可切除病例中预测生存预后不良的可靠生物标志物。FAM83A 可能通过 ERK 信号通路促进 PD-L1 的表达，从而导致肿瘤的免疫逃逸。
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