Establishment of a lncRNA-Based Prognostic Gene Signature Associated With Altered Immune Responses in HCC

Abstract

Hepatocellular carcinoma (HCC) is a common malignancy with higher mortality, and means are urgently needed to improve the prognosis. T cell exclusion (TCE) plays a pivotal role in immune evasion, and lncRNAs represent a large group of tumor development and progression modulators. Using the TCGA HCC dataset (n=374), we identified 2752 differentially expressed and 702 TCE-associated lncRNAs, of which 336 were in both groups. As identified using the univariate Cox regression analysis, those associated with overall survival (OS) were subjected to the LASSO-COX regression analysis to develop a prognosis signature. The model, which consisted of 11 lncRNAs and was named 11LNCPS for 11-lncRNA prognosis signature, was validated and performed better than two previous models. In addition to OS and TCE, higher 11LNCPS scores had a significant correlation with reduced infiltrations of CD8+ T cells and dendritic cells (DCs) and decreased infiltrations of Th1, Th2, and pro B cells. As expected, these infiltration alterations were significantly associated with worse OS in HCC. Analysis of published data indicates that HCCs with higher 11LNCPS scores were transcriptomically similar to those that responded better to PDL1 inhibitor. Of the 11LNCPS lncRNAs, LINC01134 and AC116025.2 seem more crucial, as their upregulations affected more immune cell types’ infiltrations and were significantly associated with TCE, worse OS, and compromised immune responses in HCC. LncRNAs in the 11LNCPS impacted many cancer-associated biological processes and signaling pathways, particularly those involved in immune function and metabolism. The 11LNCPS should be useful for predicting prognosis and immune responses in HCC.

Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma

“…The alteration of lncRNAs is also involved in immune response in cancers, including the regulation of immune checkpoint expression and tumor microenvironment composition [ 9 ]. Regarding HCC, it was shown that an up-regulated lncRNAs signature was associated with increased immune infiltration and worse overall survival [ 10 ].…”

LINC01134 promotes the progression of colorectal cancer through enhancing SLC1A5 mRNA stability

“…Previous studies have shown that LINC01134 was highly expressed in CHOL, COAD, LAML, LIHC [7,8,19], PRAD and READ tissues compared with corresponding normal tissues (Figure S1A). Thus, further analysis was conducted to identify the correlation between LINC01134 and colorectal cancer (CRC) via the online tool GEPIA (http://gepia.cancer-pku.cn/detail.php) [15].…”

Construction and validation of a prognostic signature for mucinous colonic adenocarcinoma based on N7-methylguanosine-related long non-coding RNAs

“…LINC01133 has been shown to play an important role in the occurrence and development of gastric ( 43 ), epithelial ovarian ( 44 ), cervical ( 45 ), and pancreatic cancers ( 46 ). LINC01134 has been proven to be relevant to immune response and metabolism in hepatocellular carcinoma (HCC) and has also been identified as an effective biomarker for HCC treatment ( 47 , 48 ). Furthermore, MHENCR has been found to be a predictor of poor prognosis in CRC patients and a regulator of tumourigenesis through the inhibition of miR-532-p ( 49 ).…”