A prognostic aging-related lncRNA risk model correlates with the immune microenvironment in HCC
Authors: Mei Kun , Chen Zilu , Wang Qin , Ali Akbar , Huang Yan , Yi Luo 
Published: January 2024

<p style="margin-top: 12.0pt; text-align: justify; text-justify: inter-ideograph;"><strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Background:&nbsp;</span></strong><span lang="EN-US" style="font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Hepatocellular carcinoma (HCC) stands out as one of the most lethal cancers globally, given its complexity, recurrence following surgical resection, metastatic potential, and inherent heterogeneity.</span><strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">&nbsp;</span></strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">In<strong> </strong></span><span lang="EN-US" style="font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">recent years, researchers have systematically elucidated the significance of long non-coding RNA (lncRNA) in the initiation and progression of HCC. The introduction of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases has significantly enhanced the prognostic assessment of HCC. However, the association between HCC and cell senescence has been infrequently explored in the literature. </span><strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Method:</span></strong><span lang="EN-US" style="font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">&nbsp;We downloaded liver hepatocellular carcinoma (LIHC)-related messenger RNA and lncRNA expression levels from TCGA. Correlation analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to validate the lncRNA risk model associated with cellular aging. Comparing the infiltration of diverse immune cells enabled the identification of distinct differences in the immunological microenvironments of the two risk groups. Subsequently, we conducted a real-time polymerase chain reaction (qPCR) experiment to confirm the accuracy of the selected lncRNAs. </span><strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Results:</span></strong><span lang="EN-US" style="font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">&nbsp;A predictive framework for HCC was constructed based on the expression levels of five lncRNAs. Multivariate and univariate Cox regression analyses revealed that lncRNA signatures associated with senescence were independently correlated with an increased risk of HCC. Additionally, the nomogram also provides a more refined and sensitive model. Further investigation into the variations in immune cells and functions between the high-risk and low-risk groups was conducted. Subsequently, a qPCR experiment results revealed underexpression of AC068756.1, AC090578.1, AC145343.1, and LINC0022 in Huh7 and LM3 cells. In contrast, AP003392.4 did not exhibit a significant difference between Huh7 and control cells. </span><strong><span lang="EN-US" style="font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">Conclusion:</span></strong><span lang="EN-US" style="font-size: 10.5pt; font-family: Nunito; mso-bidi-font-family: 'Times New Roman'; mso-bidi-theme-font: minor-bidi; color: #212529; background: white;">&nbsp;The prognostic features and nomogram, consisting of five aging-related lncRNAs (AC068756.1, AC090578.1, AC145343.1, AP003392.4, and LINC00221), may be useful in predicting the overall survival of HCC.</span></p>