肝细胞癌中细胞黏附分子基因的表达及其预后、生物学意义的综合分析。

Comprehensive Analysis of the Expression of Cell Adhesion Molecules Genes in Hepatocellular Carcinoma and their Prognosis, and Biological Significance.

机构信息

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China.

Qidong Liver Cancer Institute, Qidong People's Hospital, the affiliated Qidong Hospital of Nantong University, 226200 Nantong, Jiangsu, China.

出版信息

Front Biosci (Landmark Ed). 2024 Feb 21;29(2):76. doi: 10.31083/j.fbl2902076.

DOI:10.31083/j.fbl2902076

PMID:38420809

Abstract

BACKGROUND

Collagen-related cell adhesion molecules (CAMs) are a major component of the extracellular matrix (ECM) and often accumulate in the liver during chronic liver disease or hepatocellular carcinoma (HCC). In this study we identified several promising collagens related to CAMs that may be of clinical use for the diagnosis and prognosis of HCC.

METHODS

We obtained multi-omics data including RNA sequencing (RNA-Seq) data, microarray data, proteomic data from the TCGA, GEO databases, GTEx, and NODE. Bioinformatics analyses were then performed to investigate correlations between the expression patterns of significant genes and HCC. Tumor tissue and para-cancerous tissue samples from HCC patients were also used to validate the results using RT-PCR.

RESULTS

A literature research and LASSO-COX analysis identified three significant collagen-related CAM genes: , , and . Immunohistochemistry images in the Human Protein Atlas Project database showed that SERPINH1 and ITGB1 proteins were moderately or highly expressed in HCC tumor tissues compared to para-cancerous tissue, whereas DCN expression was lower in HCC tumor tissue. These results were validated by RT-PCR. Low- and high-risk groups of HCC patients were distinguished by the logistic panel in the TCGA database. These showed significantly different prognosis, clinicopathological features, and immune cell infiltration. Logistic regression was used to construct predictive models based on the individual expression levels of , , and . These showed highly accurate diagnostic ability (AUC = 0.987).

CONCLUSIONS

The current findings suggest that the collagen-related CAMs , , and may be potential therapeutic targets in HCC. Logistic panels of , and could serve as non-invasive and effective diagnostic biomarkers for HCC.

CLINICAL TRIAL REGISTRATION

Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (https://clinicaltrials.gov/).

摘要

背景

胶原相关细胞黏附分子（CAMs）是细胞外基质（ECM）的主要成分，在慢性肝病或肝细胞癌（HCC）中常积聚在肝脏中。本研究中，我们鉴定了几种有希望的与 CAM 相关的胶原，它们可能对 HCC 的诊断和预后具有临床应用价值。

方法

我们从 TCGA、GEO 数据库、GTEx 和 NODE 数据库中获取了包括 RNA 测序（RNA-Seq）数据、微阵列数据和蛋白质组学数据在内的多组学数据。然后进行生物信息学分析，以研究显著基因的表达模式与 HCC 之间的相关性。还使用 RT-PCR 验证了 HCC 患者肿瘤组织和癌旁组织样本的结果。

结果

文献研究和 LASSO-COX 分析鉴定了三个显著的胶原相关 CAM 基因：、和。在 Human Protein Atlas 项目数据库的免疫组化图像中，与癌旁组织相比，SERPINH1 和 ITGB1 蛋白在 HCC 肿瘤组织中呈中度或高度表达，而 DCN 表达在 HCC 肿瘤组织中较低。这些结果通过 RT-PCR 得到了验证。在 TCGA 数据库中，通过逻辑面板区分了 HCC 患者的低风险和高风险组。这些组显示出明显不同的预后、临床病理特征和免疫细胞浸润。使用逻辑回归基于个体的表达水平构建了基于、和的预测模型。这些模型具有很高的诊断准确性（AUC=0.987）。