CNHPP_Liver

Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.

肝细胞癌（Hepatocellular carcinoma, HCC）约占原发性肝癌的90%，是全球第二大癌症相关死亡病因。尽管早期肝细胞癌可通过手术治疗实现根治，但患者五年总生存率仅为50%~70%。蛋白质组学技术的进步拓展了癌症蛋白质组表征的广度与深度。本研究针对临床早期肝细胞癌（巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）0期及A期）的222例肿瘤组织与配对癌旁正常组织开展蛋白质组学分析，是目前规模最大的此类表征工作。定量蛋白质组学数据将该早期肝细胞癌队列划分为三种更为精细的亚型（命名为S-I、S-II及S-III），各亚型临床结局存在显著差异。其中S-I亚型保留了肝脏解毒与代谢功能，预后最佳；S-II亚型的增殖相关分子表达水平升高；S-III亚型则显著富集肿瘤转移与免疫应答通路，预后最差。目前经美国食品药品监督管理局（Food and Drug Administration, FDA）批准的肝细胞癌治疗药物，以及处于肝细胞癌临床研究阶段的抑制剂所靶向的各亚型特异性特征，为肝细胞癌治疗靶点研究提供了全新资源。研究还在S-III亚型中发现了一种全新的胆固醇稳态紊乱伴胆固醇酯异常蓄积的机制。综上，本研究首次完成了早期肝细胞癌的蛋白质组学分型，为肿瘤生物学研究及个性化靶向治疗提供了全新的研究视角。

搜集汇总

背景与挑战

背景概述

CNHPP_Liver是一个专注于肝细胞癌（HCC）的蛋白质组学数据集，包含222个早期HCC肿瘤和配对非肿瘤组织的定量蛋白质组数据，用于识别三种具有不同临床预后和生物学特征的亚型。该数据集规模达2.19TB，主要由质谱原始文件构成，由北京蛋白质组研究中心于2019年创建并公开共享，为HCC的肿瘤生物学研究和个性化靶向治疗提供了重要资源。