Wang Wei, Li Qiang, Huang Ge, Lin Bing-Yao, Lin Dongzi, Ma Yan, Zhang Zhao, Chen Tao, Zhou Jie
Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China.
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510000, People's Republic of China.
Onco Targets Ther. 2021 Feb 12;14:1007-1020. doi: 10.2147/OTT.S273823. eCollection 2021.
The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation.
Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC-MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC).
A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC.
A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC.
肝细胞癌（HCC）预后较差，这促使我们去发现早期有效的生物标志物。在本研究中，我们应用基于串联质谱标签（TMT）的蛋白质组学分析来发现用于HCC识别和鉴别诊断的潜在蛋白质标志物。
纳入15例患者，包括高分化（G1，n = 5）、中分化（G2，n = 5）和低分化（G3，n = 5），共有30对匹配组织（肿瘤组织和来自同一患者的相邻非肿瘤组织）。所有样本均进行TMT标记和液相色谱-串联质谱（LC-MS/MS）分析。随后将鉴定出的蛋白质进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）注释以预测其功能。通过免疫组织化学（IHC）对鉴定出的蛋白质候选物进行验证。
共鉴定出1010种蛋白质。其中，肿瘤组织与相邻非肿瘤组织之间发现154种差异表达蛋白（DEP），100种上调，54种下调；G1和G3组织之间发现12种DEP，9种上调，3种下调；G1和G2组织之间发现8种DEP，5种上调，3种下调；G2和G3组织之间发现11种DEP，8种上调，3种下调。其中，与G1和G2肿瘤相比，G3肿瘤中精氨酸琥珀酸合成酶1（ASS1）和氨基甲酰磷酸合成酶1（CPS1）显著上调，而尿卟啉原脱羧酶（UROD）和血红蛋白β（HBB）显著下调。与G2和G3肿瘤相比，G1肿瘤中有3种蛋白质，即细胞色素b5A（CYB5A）、FK506结合蛋白11（FKBP11）和Y-盒结合蛋白1（YBX1）显著上调。通过免疫组织化学进一步验证了7种候选生物标志物。
鉴定出多种与HCC组织学分化相关的DEP，其中ASS1、CPS1、UROD和HBB蛋白是区分低分化HCC的潜在生物标志物，而CYB5A、FKBP11和YBX1是区分高分化HCC的潜在生物标志物。我们的研究结果可能进一步为HCC的诊断和预后提供新的见解。
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