Identification of mutation gene prognostic biomarker in multiple myeloma through gene panel exome sequencing and transcriptome analysis in Chinese population

Chunbao Xie; Ling Zhong; Jiangrong Luo; Ji Luo; Yingmiao Wu; Shuai Zheng; Lingxi Jiang; Jianbo Zhang; Yi Shi

doi:10.1016/j.compbiomed.2023.107224

Identification of mutation gene prognostic biomarker in multiple myeloma through gene panel exome sequencing and transcriptome analysis in Chinese population

Comput Biol Med. 2023 Sep:163:107224. doi: 10.1016/j.compbiomed.2023.107224. Epub 2023 Jul 3.

Authors

Chunbao Xie¹, Ling Zhong², Jiangrong Luo³, Ji Luo⁴, Yingmiao Wu⁴, Shuai Zheng⁴, Lingxi Jiang⁵, Jianbo Zhang⁶, Yi Shi⁷

Affiliations

¹ Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
² Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
³ Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁴ School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁵ Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China. Electronic address: jlx160606@126.com.
⁶ Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address: 178508311@qq.com.
⁷ Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China. Electronic address: shiyi1614@126.com.

PMID: 37406588
DOI: 10.1016/j.compbiomed.2023.107224

Abstract

Background: The 5-year survival rate of multiple myeloma (MM) in China is less than 40%, with considerable individual heterogeneity. Gene mutations are important predictive biomarkers that influence MM treatment decision. The aim of our study was to uncover the clinical significance of mutated genes in MM in the Chinese population.

Methods: Targeted exon panel sequencing was performed of 400 genes to detect the gene mutation status in plasma cells from 50 patients with MM. DAVID was used to explore the functions and pathways of mutated genes. Detection of mutant gene expression, prognosis and immune cell infiltration with GSE6477. GEO2R was utilized to identify differentially expressed genes (DEGs). Kaplan-Meier and CIBERSORT were applied to compare survival distributions and evaluate the gene expression associated with immune cell infiltration, respectively.

Results: Mutations of 337 genes were identified in MM. The mutation types included SNP, INS, and DEL, but the dominant mutation type was SNP. Function and pathway analysis of mutant genes were performed to elucidate DNA modifications. We identified a total number of 660 downregulated and 587 upregulated genes from the GSE6477 dataset. Thirty-three common genes were present in both the mutant genes and DEGs. The functions and pathways of the mutated genes were enriched in myeloid cell differentiation, regulation of hemopoiesis, etc. Moreover, we found that the low expression of BCL6, BIRC3, HLA-DQA1, and VCAN was correlated with poor prognosis in MM.

Conclusions: The mutations and low expression of BCL6, BIRC3, HLA-DQA1, and VCAN were correlated with poor prognosis and immune cell infiltration in MM. This study is the first to reveal the spectrum of mutations in the Chinese population by the use of an NGS panel.

Keywords: Exome sequencing; Gene panel; Multiple myeloma; Mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
East Asian People
Exome Sequencing
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Multiple Myeloma* / genetics
Mutation / genetics
Prognosis
Transcriptome

Substances

Biomarkers
Biomarkers, Tumor
VCAN protein, human
HLA-DQA1 antigen
BIRC3 protein, human
BCL6 protein, human