基于失巢凋亡相关基因的食管鳞癌预后风险模型的建立与验证。

Establishment and validation of the prognostic risk model based on the anoikis-related genes in esophageal squamous cell carcinoma.

机构信息

Henan Medical key Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang, China.

出版信息

Ann Med. 2024 Dec;56(1):2418338. doi: 10.1080/07853890.2024.2418338. Epub 2024 Oct 23.

DOI:10.1080/07853890.2024.2418338

PMID:39444152

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11504171/

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a malignant condition in humans. Anoikis-related genes (ARGs) are crucial to cancer progression. Therefore, more studies on the relationship between ARGs and ESCC are warranted.

METHODS

The study acquired ESCC-related transcriptome data from TCGA. Differentially expressed ARGs (DE-ARGs) were obtained by differential analysis and candidates were filtered out by survival analysis. Prognostic genes were determined by Cox and LASSO regression. A risk model was constructed based on prognostic gene expressions. An immune infiltration study was done to explain how these genes contribute to ESCC development. The IC50 test was adopted to assess the clinical response of chemotherapy drugs. Single cell analysis was performed on the GSE145370 dataset. Moreover, the prognostic gene expressions were detected by qRT-PCR.

RESULTS

53 DE-ARGs were screened and four candidate genes including PBK, LAMC2, TNFSF10 and KL were obtained. Cox and LASSO regression identified the two prognostic genes, TNFSF10 and PBK. Immuno-infiltration analysis revealed positive associations of PBK with Macrophages M0 cells, and TNFSF10 with Macrophages M1 cells. The IC50 values of predicted drugs, in the case of Tozasertib 1096 and WIKI4 1940, were significantly variant between risk groups. Single cell analysis revealed that TNFSF10 and PBK levels were higher in epithelial cells than in other cells. The prognostic genes expression results by qRT-PCR were compatible with the dataset analysis.

CONCLUSION

The study established an ARG prognosis model of ESCC. It provided a reference for the research of ARGs in ESCC.

摘要

背景

食管鳞状细胞癌（ESCC）是人类的一种恶性疾病。凋亡相关基因（ARGs）对癌症的进展至关重要。因此，需要更多的研究来探讨 ARGs 与 ESCC 之间的关系。

方法

本研究从 TCGA 中获取了 ESCC 相关的转录组数据。通过差异分析获得差异表达的 ARGs（DE-ARGs），并通过生存分析筛选候选基因。通过 Cox 和 LASSO 回归确定预后基因。基于预后基因表达构建风险模型。进行免疫浸润研究，以解释这些基因如何促进 ESCC 的发展。采用 IC50 试验评估化疗药物的临床反应。对 GSE145370 数据集进行单细胞分析。此外，通过 qRT-PCR 检测预后基因的表达。

结果

筛选出 53 个 DE-ARGs，获得了 4 个候选基因，包括 PBK、LAMC2、TNFSF10 和 KL。Cox 和 LASSO 回归确定了 TNFSF10 和 PBK 这两个预后基因。免疫浸润分析表明，PBK 与巨噬细胞 M0 细胞呈正相关，TNFSF10 与巨噬细胞 M1 细胞呈正相关。在预测药物中，Tozasertib 1096 和 WIKI4 1940 的 IC50 值在风险组之间存在显著差异。单细胞分析显示，TNFSF10 和 PBK 在上皮细胞中的表达水平高于其他细胞。qRT-PCR 检测到的预后基因表达结果与数据集分析结果一致。