Integrated Analysis of Single-cell and Bulk RNA Sequencing Reveals a Malignancy-related Signature in Lung Adenocarcinoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Jul 10

PMID 37427142

Authors

Mengxi Wu

Zhenyu Wu

Jun Yan

Jie Zeng

Jun Kuang

Chenghua Zhong

Xiaojia Zhu

Yijun Mo

Quanwei Guo

Dongfang Li

Jianfeng Tan

Tao Zhang

Jianhua Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. The research strived to establish a prognostic model based on malignancy-related risk score (MRRS) in LUAD.

Methods: We applied the single-cell RNA sequencing (scRNA-seq) data from Tumor Immune Single Cell Hub database to recognize malignancy-related geneset. Meanwhile, we extracted RNA-seq data from The Cancer Genome Atlas database. The GSE68465 and GSE72094 datasets from the Gene Expression Omnibus database were downloaded to validate the prognostic signature. Random survival forest analysis screened MRRS with prognostic significance. Multivariate Cox analysis was leveraged to establish the MRRS. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the malignancy-related signature. In addition, we used qRT-PCR to explore the expression profile of MRRS-constructed genes in LUAD cells.

Results: The scRNA-seq analysis revealed the markers genes of malignant celltype. The MRRS composed of 7 malignancy-related genes was constructed for each patient, which was shown to be an independent prognostic factor. The results of the GSE68465 and GSE72094 datasets validated MRRS's prognostic value. Further analysis demonstrated that MRRS was involved in oncogenic pathways, genetic mutations, and immune functions. Moreover, the results of qRT-PCR were consistent with bioinformatics analysis.

Conclusion: Our research recognized a novel malignancy-related signature for predicting the prognosis of LUAD patients and highlighted a promising prognostic and treatment marker for LUAD patients.

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