Integration of single-cell regulon atlas and multi-omics data for prognostic stratification and personalized treatment prediction in human lung adenocarcinoma

Yi Xiong; Yihao Zhang; Na Liu; Yueshuo Li; Hongwei Liu; Qi Yang; Yu Chen; Zhizhi Xia; Xin Chen; Siyi Wanggou; Xuejun Li

doi:10.1186/s12967-023-04331-z

Integration of single-cell regulon atlas and multi-omics data for prognostic stratification and personalized treatment prediction in human lung adenocarcinoma

J Transl Med. 2023 Jul 25;21(1):499. doi: 10.1186/s12967-023-04331-z.

Authors

Yi Xiong^#^{1

2

3}, Yihao Zhang^#^{1

2

3}, Na Liu^{1

2

4}, Yueshuo Li^{1

2

4}, Hongwei Liu^{1

2}, Qi Yang^{1

2}, Yu Chen³, Zhizhi Xia⁵, Xin Chen⁶, Siyi Wanggou^{7

8}, Xuejun Li^{9

10}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
² Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
³ Xiangya School of Medicine, Central South University, Changsha, 410013, China.
⁴ Postdoctoral Research Workstation, Xiangya Hospital, Central South University, Hunan, 410078, China.
⁵ Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁶ Songjiang Research Institute, Shanghai Songjiang District Central Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 201600, China. xinchen@shsmu.edu.cn.
⁷ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. zokygwong@gmail.com.
⁸ Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. zokygwong@gmail.com.
⁹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. lxjneuro@csu.edu.cn.
¹⁰ Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. lxjneuro@csu.edu.cn.

^# Contributed equally.

Abstract

Transcriptional programs are often dysregulated in cancers. A comprehensive investigation of potential regulons is critical to the understanding of tumorigeneses. We first constructed the regulatory networks from single-cell RNA sequencing data in human lung adenocarcinoma (LUAD). We next introduce LPRI (Lung Cancer Prognostic Regulon Index), a precision oncology framework to identify new biomarkers associated with prognosis by leveraging the single cell regulon atlas and bulk RNA sequencing or microarray datasets. We confirmed that LPRI could be a robust biomarker to guide prognosis stratification across lung adenocarcinoma cohorts. Finally, a multi-omics data analysis to characterize molecular alterations associated with LPRI was performed from The Cancer Genome Atlas (TCGA) dataset. Our study provides a comprehensive chart of regulons in LUAD. Additionally, LPRI will be used to help prognostic prediction and developing personalized treatment for future studies.

Keywords: Chemotherapy and immunotherapy; LPRI; LUAD; Prognostic model; Single cell RNA sequencing; TCGA; TME; Transcriptional regulation.

Publication types

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

MeSH terms

Adenocarcinoma of Lung* / genetics
Humans
Lung Neoplasms* / genetics
Multiomics
Precision Medicine
Prognosis
Regulon