Identification of a molecular subtyping system associated with the prognosis of Asian hepatocellular carcinoma patients receiving liver resection

Abstract

Hepatocellular carcinoma (HCC) remains a severe health issue worldwide, especially in Asia. To date, molecular classifications proposed for the overall survival (OS) or recurrence-free survival (RFS) prediction of Asian HCC patients after hepatectomy are quite few and limited in clinical practice. Here, we established a molecular subtyping system for Asian HCC to facilitate prognosis evaluation. Firstly, differentially expressed genes (DEGs) (FDR [false discovery rate] <0.05) between different types of liver cancer and non-tumor tissue were screened. Among the DEGs solely between HCC and non-tumor samples, 185 genes simultaneously significantly associated with the OS and RFS were identified as HCC-characteristic genes. The molecular subtypes were developed based on the expression profiles of the 185 genes in the training dataset (TCGA [The Cancer Genome Atlas] dataset) using non-negative matrix factorization (NMF) clustering method. Patients were then classified into Subtype1 and Subtype2 groups denoting unfavorable and favorable clinical outcome respectively. The robustness and effectiveness of the molecular subtype was confirmed in another independent dataset (GSE14520) by the same clustering approach and Kaplan-Meier analyses. Moreover, functional prediction analysis revealed that the identified molecular signature was involved in chemotaxis, apoptosis and cell development associated pathways. Besides, the molecular signature was closely related to the clinical characteristics including TNM stage, preoperative alpha-fetoprotein (AFP) level and TP53 mutation. Furthermore, integration of the molecular subtype and TNM stage was demonstrated to improve risk stratification. Taken together, our molecular subtyping system exhibited great utility and potential in prognosis prediction and therapeutic decision making of Asian HCC patients.

An independent poor-prognosis subtype of hepatocellular carcinoma based on the tumor microenvironment

“…A similar observation of three patient clusters with increasing levels of immune cell infiltration in breast cancer has been reported. Additionally, Ma et al 32 established a molecular subtyping method for Asian HCC to evaluate prognosis. Therefore, the importance of conducting a systematic analysis of the molecular subtypes of HCC is evident.…”

“…Additionally, Ma et al. 32 established a molecular subtyping method for Asian HCC to evaluate prognosis. Therefore, the importance of conducting a systematic analysis of the molecular subtypes of HCC is evident.…”

Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma

“…Tumor metastasis plays a major role in the poor prognosis of HCC patients. Although HCC has many staging systems, such as the American Joint Committee on Cancer (AJCC) TNM stage and the Barcelona-Clinic Liver Cancer (BCLC) system, approaches for evaluation of survival and prognosis of patients are limited [ 3 ]. Therefore, there is a need to develop a novel metastasis-related signature for improved prediction of prognosis of HCC patients.…”

Multi-resolution characterization of molecular taxonomies in bulk and single-cell transcriptomics data

“…Common deliverables of these types of analysis include the discovery and characterization of molecular subtypes, which are prevalent in both bulk and single-cell gene expression studies. For example, TCGA bulk expression data have been utilized to characterize subtypes of numerous cancers ( 7 ), including but not limited to: breast ( 8 ), colorectal ( 9 ), liver ( 10 ) and bladder cancer ( 11 , 12 ). Similarly, the characterization of molecular subtypes is a standard component of the scRNAseq data analysis workflow, insofar as estimation and annotation of subpopulations of cells is one of the primary goals of the assay ( 13 ).…”