Classification of the mitochondrial ribosomal protein-associated molecular subtypes and identified a serological diagnostic biomarker in hepatocellular carcinoma
作者全名："Xie, Cong; Hu, Juan; Hu, Qin; Jiang, Linshan; Chen, Weixian"
作者地址："[Xie, Cong; Hu, Juan; Hu, Qin; Jiang, Linshan; Chen, Weixian] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing, Peoples R China"
通信作者："Chen, WX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing, Peoples R China."
来源：FRONTIERS IN SURGERY
关键词：mitochondrial ribosomal protein; molecular subtype; mrpl9; hepatocellular carcinoma; biomarker
摘要："PurposeThe objective of this study was to sort out innovative molecular subtypes associated with mitochondrial ribosomal proteins (MRPs) to predict clinical therapy response and determine the presence of circulating markers in hepatocellular carcinoma (HCC) patients. MethodsUsing an unsupervised clustering method, we categorized the relative molecular subtypes of MRPs in HCC patients. The prognosis, biological properties, immune checkpoint inhibitor and chemotherapy response of the patients were clarified. A signature and nomogram were developed to evaluate the prognosis. Enzyme-linked immunosorbent assay (ELISA) measured serum mitochondrial ribosomal protein L9 (MRPL9) levels in liver disease patients and normal individuals. Receiver operating characteristic (ROC) curves were conducted to calculate the diagnostic effect. The Cell Counting Kit 8 was carried out to examine cell proliferation, and flow cytometry was used to investigate the cell cycle. Transwell assay was applied to investigate the potential of cell migration and invasion. Western blot detected corresponding changes of biological markers. ResultsParticipants were classified into two subtypes according to MRPs expression levels, which were characterized by different prognoses, biological features, and marked differences in response to chemotherapy and immune checkpoint inhibitors. Serum MRPL9 was significantly higher in HCC patients than in normal individuals and the benign liver disease group. ROC curve analysis showed that MRPL9 was superior to AFP and Ferritin in differentiating HCC from healthy and benign patients, or alone. Overexpressed MRPL9 could enhance aggressiveness and facilitate the G1/S progression in HCC cells. ConclusionWe constructed novel molecular subtypes based on MRPs expression in HCC patients, which provided valuable strategies for the prediction of prognosis and clinical personalized treatment. MRPL9 might act as a reliable circulating diagnostic biomarker and therapeutic target for HCC patients."
基金机构：National Natural Science Foundation of China 
基金资助正文："The current study was granted by the National Natural Science Foundation of China, no. 8187080942."