Huang Shih-Chung, Huang Chao-Cheng, Ko Chou-Yuan, Huang Cheng-Yi, Liu Ching-Han, Lee Yung-Kuo, Chen Tung-Yuan, Hsueh Chao-Wen, Tzou Shiow-Jyu, Tai Ming-Hong, Hu Tsung-Hui, Tsai Ming-Chao, Lee Wen-Chin, Ho Yu-Cheng, Wu Cheng-Chun, Chang Yi-Chen, Chang Jung-Jui, Liu Kai-Hsi, Li Chiao-Ching, Wen Zhi-Hong, Chang Chen-Lin, Chu Tian-Huei
Department of Internal Medicine, Division of Cardiology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Gene. 2023 May 20;865:147331. doi: 10.1016/j.gene.2023.147331. Epub 2023 Mar 5.
Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.
慢肌肌钙蛋白T（TNNT1）作为一种预后不良指标，在结肠癌和乳腺癌中上调。然而，TNNT1在肝细胞癌（HCC）疾病预后和生物学功能中的作用仍不清楚。应用癌症基因组图谱（TCGA）、实时定量逆转录聚合酶链反应（qRT-PCR）、免疫印迹和免疫组织化学分析来评估人HCC中TNNT1的表达。使用TCGA分析研究TNNT1水平对疾病进展和生存结果的影响。此外，利用生物信息学分析和HCC细胞培养来研究TNNT1的生物学功能。此外，分别使用免疫印迹分析和酶联免疫吸附测定（ELISA）检测HCC细胞的细胞外TNNT1和HCC患者的循环TNNT1。在培养的肝癌细胞中进一步验证了TNNT1中和对致癌行为和信号传导的影响。在本研究中，基于生物信息学、新鲜组织、石蜡切片和血清分析，HCC患者的肿瘤和血液中的TNNT1上调。从多种生物信息学工具来看，TNNT1过表达与HCC患者的晚期、高分级、转移、血管侵犯、复发和不良生存结果相关。通过细胞培养和TCGA分析，TNNT1的表达和释放与HCC组织和细胞中的上皮-间质转化（EMT）过程呈正相关。此外，TNNT1中和抑制了肝癌细胞的致癌行为和EMT。总之，TNNT1可能作为HCC管理的非侵入性生物标志物和药物靶点。这一研究发现可能为HCC的诊断和治疗提供新的见解。
