Machine learning integrations develop an antigen-presenting-cells and T-Cells-Infiltration derived LncRNA signature for improving clinical outcomes in hepatocellular carcinoma
Xiaodong Wang,
Ji Chen,
Lifan Lin,
Yifei Li,
Qiqi Tao,
Zhichao Lang,
Jianjian Zheng,
Zhengping Yu
Affiliations
Xiaodong Wang
Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University
Ji Chen
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Lifan Lin
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Yifei Li
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Qiqi Tao
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Zhichao Lang
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Jianjian Zheng
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
Zhengping Yu
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University
Abstract As a highly heterogeneous cancer, the prognostic stratification and personalized management of hepatocellular carcinoma (HCC) are still challenging. Recently, Antigen-presenting-cells (APCs) and T-cells-infiltration (TCI) have been reported to be implicated in modifying immunology in HCC. Nevertheless, the clinical value of APCs and TCI-related long non-coding RNAs (LncRNAs) in the clinical outcomes and precision treatment of HCC is still obscure. In this study, a total of 805 HCC patients were enrolled from three public datasets and an external clinical cohort. 5 machine learning (ML) algorithms were transformed into 15 kinds of ML integrations, which was used to construct the preliminary APC-TCI related LncRNA signature (ATLS). According to the criterion with the largest average C-index in the validation sets, the optimal ML integration was selected to construct the optimal ATLS. By incorporating several vital clinical characteristics and molecular features for comparison, ATLS was demonstrated to have a relatively more significantly superior predictive capacity. Additionally, it was found that the patients with high ATLS score had dismal prognosis, relatively high frequency of tumor mutation, remarkable immune activation, high expression levels of T cell proliferation regulators and anti-PD-L1 response as well as extraordinary sensitivity to Oxaliplatin/Fluorouracil/Lenvatinib. In conclusion, ATLS may serve as a robust and powerful biomarker for improving the clinical outcomes and precision treatment of HCC.
