STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion.
STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion.
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STAM 通过抑制细胞生长和侵袭来延长透明细胞肾细胞癌患者的生存期
DOI：
10.3389/fonc.2021.611081
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zeng G
中科院分区：
文献类型：
--
作者：
Deng T;He Z;Duan X;Gu D;Cai C;Wu W;Liu Y;Zeng G
背景：信号转导衔接分子1（STAM1）被认为介导细胞生长并参与多种信号通路；然而，目前尚未发表任何关于 STAM1 在任何肿瘤中的作用的研究。我们的研究旨在探讨 STAM1 对透明细胞肾细胞癌 (ccRCC) 的预后价值及其在调节癌细胞功能中的作用。方法：使用 2019 年 12 月癌症基因组图谱 (TCGA) 的数据来检查 STAM1 在指示 ccRCC 患者生存中的作用。使用购买的组织微阵列 (TM) 和新鲜的 ccRCC 肾组织进行进一步验证。然后，STAM1 在人 ccRCC 细胞系中过表达用于体外测定。最后，采用生物信息学方法进行 STAM1 蛋白-蛋白相互作用 (PPI) 网络构建和功能分析。结果：TCGA 队列共纳入 539 个 ccRCC 和 72 个对照样本，TM 队列共纳入 149 个 ccRCC 和 29 个对照样本。在 TCGA 和 TM 队列中，我们发现 ccRCC 中的 STAM1 表达低于正常的邻近非癌性肾组织（两个队列的 P < 0.0001）。 STAM1 下调还与显着缩短的总生存期 (OS) 相关（两个队列的 P < 0.0001）。在 TCGA 队列中，STAM1 表达减少也与肿瘤的侵袭性特征相关。多变量分析显示，在 TCGA（HR = 0.52，95% CI：0.33-0.84，P = 0.007）和 TM 队列（HR = 0.12，95% CI：0.04-0.32，P < 0.001）中，STAM1 被证明是 ccRCC 生存的独立预后因素。我们的体外实验表明，STAM1 抑制 ccRCC 细胞系的细胞活力、侵袭和迁移。在PPI网络中，发现分为5个生物过程的10个候选基因与STAM1密切相关。结论：STAM1 是一种有前途的预测 ccRCC 生存结果的预后生物标志物。我们的体外实验证明了初步发病机制。 STAM1 调节 ccRCC 的进一步病理机制需要全面的实验室和临床研究。
Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function. Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein–protein interaction (PPI) network construction and functional analyses. Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P < 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P < 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33–0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04–0.32, P < 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1. Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies.
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作者：
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通讯作者：
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