Zou Wenbo, Wang Zizheng, Zhang Xiuping, Xu Shuai, Wang Fei, Li Lincheng, Deng Zhaoda, Wang Jing, Pan Ke, Ge Xinlan, Li Chonghui, Liu Rong, Hu Minggen
Medical School of Chinese PLA, Beijing, China.
Faculty of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, China.
Cancer Cell Int. 2021 Dec 7;21(1):657. doi: 10.1186/s12935-021-02310-2.
Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer, and its long-term survival rate remains poor. RNA-binding proteins (RBPs) play an important role in critical cellular processes, failure of any one or more processes can lead to the development of multiple cancers. This study aimed to explore pivotal biomarkers and corresponding mechanisms to predict the prognosis of patients with ICC.
The transcriptomic and clinical information of patients were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Bioinformatic methods were used to identify survival-related and differentially-expressed biomarkers. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to detect the expression levels of key biomarkers in independent real-world cohorts. Subsequently, a prognostic signature was constructed that effectively distinguished patients in the high- and low-risk groups. Independent prognosis analysis was used to verify the signature's independent predictive capabilities, and two nomograms were developed to predict survival.
PIWIL4 and SUPT5H were identified and considered as pivotal biomarkers, and the same expression trends of upregulation in ICC were also validated via qRT-PCR and immunohistochemistry in the separate real-world sample cohorts. The prognostic signature showed good predictive capabilities according to the area under the curve. The correlation of the biomarkers with the tumour microenvironment suggested that the high riskScore was positively related to the enrichment of resting natural killer cells and activated memory CD4 + T cells.
In the present study, we demonstrated that PIWIL4 and SUPT5H could be used as novel prognostic biomarkers to develop a prognostic signature. This study provides potential biomarkers of prognostic value for patients with intrahepatic cholangiocarcinoma.
肝内胆管癌（ICC）是一种致命的原发性肝癌，其长期生存率仍然很低。RNA结合蛋白（RBPs）在关键的细胞过程中发挥着重要作用，任何一个或多个过程的失败都可能导致多种癌症的发生。本研究旨在探索预测ICC患者预后的关键生物标志物及其相应机制。
从癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）收集患者的转录组学和临床信息。采用生物信息学方法鉴定与生存相关和差异表达的生物标志物。运用定量实时聚合酶链反应（qRT-PCR）和免疫组织化学检测独立真实世界队列中关键生物标志物的表达水平。随后，构建了一个预后特征，有效地区分了高风险组和低风险组的患者。采用独立预后分析验证该特征的独立预测能力，并绘制了两个列线图来预测生存情况。
鉴定出PIWIL4和SUPT5H并将其视为关键生物标志物，在独立的真实世界样本队列中通过qRT-PCR和免疫组织化学也验证了它们在ICC中上调的相同表达趋势。根据曲线下面积，预后特征显示出良好的预测能力。生物标志物与肿瘤微环境的相关性表明，高风险评分与静息自然杀伤细胞和活化记忆CD4 + T细胞的富集呈正相关。
在本研究中，我们证明PIWIL4和SUPT5H可作为新的预后生物标志物来构建预后特征。本研究为肝内胆管癌患者提供了具有预后价值的潜在生物标志物。
