上调的免疫检查点 HHLA2 在透明细胞肾细胞癌中的作用：一种新的预后生物标志物和潜在的治疗靶点。
Upregulated immune checkpoint HHLA2 in clear cell renal cell carcinoma: a novel prognostic biomarker and potential therapeutic target.
机构信息
Department of Urology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
J Med Genet. 2019 Jan;56(1):43-49. doi: 10.1136/jmedgenet-2018-105454. Epub 2018 Jul 2.
BACKGROUND
Clear cell renal cell carcinoma (ccRCC) is a malignant urogenital cancer with high mortality; however, current progress in understanding its molecular mechanism and predicting clinical treatment outcome is limited. Therefore, this study is to evaluate the clinical significance of immune inhibitory molecular human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) in ccRCC prognosis and transcriptional regulatory network.
METHODS
Expression of in ccRCC was examined by an online database platform ONCOMINE. The ONCOMINE result was independently validated by qRT-PCR and immunohistochemistry. Kaplan-Meier survival was generated using IBM SPSS Statistics V.22. ccRCC tissues cells with high HHLA2 were sorted and subjected to microarray transcriptional profiling and analysis.
RESULTS
It was shown that expression of HHLA2 was statistically significantly increased in ccRCC tissues compared with normal renal tissues at both transcriptional and protein level. Moreover, the expression of HHLA2 was closely correlated with multiple clinicopathological features including tumour size, clinical stage and histological grade. High HHLA2 expression was associated with poor overall survival and clinical outcome. Comprehensive microarray analysis further identified thousands of HHLA2 targets including mRNA, long non-coding RNA and circular RNA that might function in various biological processes, especially, immune response.
CONCLUSION
Increased HHLA2 expression was observed in ccRCC tumour tissue, which leads to a remarkable shorter overall survival and poorer prognosis. Together with other molecular evidence, we have demonstrated that HHLA2 could be a potential prognostic biomarker for ccRCC.
背景
透明细胞肾细胞癌（ccRCC）是一种具有高死亡率的恶性泌尿生殖系统癌症；然而，目前对其分子机制的理解和预测临床治疗结果的进展有限。因此，本研究旨在评估免疫抑制分子人内源性逆转录病毒-H 长末端重复相关蛋白 2（HHLA2）在 ccRCC 预后和转录调控网络中的临床意义。
方法
通过在线数据库平台 ONCOMINE 检查 HHLA2 在 ccRCC 中的表达。ONCOMINE 结果通过 qRT-PCR 和免疫组织化学独立验证。使用 IBM SPSS Statistics V.22 生成 Kaplan-Meier 生存曲线。对 HHLA2 高表达的 ccRCC 组织细胞进行微阵列转录谱分析。
结果
结果表明，与正常肾组织相比，HHLA2 在 ccRCC 组织中的转录和蛋白水平均显著增加。此外，HHLA2 的表达与多个临床病理特征密切相关，包括肿瘤大小、临床分期和组织学分级。HHLA2 高表达与总生存期和临床预后不良相关。综合微阵列分析进一步鉴定了数千个 HHLA2 靶标，包括 mRNA、长非编码 RNA 和环状 RNA，它们可能在各种生物学过程中发挥作用，尤其是免疫反应。
结论
在 ccRCC 肿瘤组织中观察到 HHLA2 表达增加，导致总生存期显著缩短和预后不良。结合其他分子证据，我们已经证明 HHLA2 可能是 ccRCC 的潜在预后生物标志物。
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