Prognostic significance of LRRC1 in hepatocellular carcinoma and construction of relevant prognostic model

Abstract

This study aimed to elucidate the prognostic value of the leucine rich repeat containing 1 (LRRC1) gene in hepatocellular carcinoma (HCC) and to determine the effects of high and low LRRC1 expression on mutation and immune cell infiltration. We downloaded HCC mRNA-seq expression and clinical data from University of California Santa Cruz Xena. The expression of LRRC1 was compared between HCC tumor and normal samples. Tumor samples were divided according to high and low LRRC1 expression. Differentially expressed genes between the 2 groups were identified, and function, mutation, and immune cell infiltration were analyzed. Genes associated with immune cells were identified using weighted gene co-expression network analysis, and transcription factors of these genes were predicted. Moreover, a prognostic model was developed and its performance was evaluated. The expression of LRRC1 was upregulated in HCC tissues, and this indicated a poor prognosis for patients with HCC. Differentially expressed genes between high and low LRRC1 expression were significantly enriched in pathways associated with cancer, amino acid metabolism, carbohydrate metabolism, and the immune system. We identified 15 differentially infiltrated immune cells between tumors with high and low LRRC1 expression and 14 of them correlated with LRRC1 gene expression. Weighted gene co-expression network analysis identified 83 immune cell-related genes, 27 of which had prognostic value. Cyclic AMP-response element binding protein regulated annexin A5, matrix metallopeptidase 9, and LRRC1 in the transcription factor regulatory network. Finally, a prognostic model composed of 7 genes were generated, which could accurately predict the prognosis of HCC patients. The LRRC1 gene might serve as a potential immune-associated prognostic biomarker for HCC.

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3

“…Recently, LRRC1, a cytoplasmic scaffold protein, was identified as an oncogenic factor that contributes to HCC [ 29 , 35 ] and lung cancer [ 32 , 36 ]; other studies have reported that LRRC1 regulates the stemness of breast cancer stem cells to behave as a potential tumor suppressor and that in human mesenchymal stem cells (MSCs) [ 33 ], LRRC1 acts as a downstream target of PPARγ that regulates adipocyte differentiation [ 30 ]. The results of these studies together emphasize the complex roles of LRRC1 in various pathological processes.…”