The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma

Lin, Weixian1; Wang, Jiaren2; Ge, Jing3; Zhou, Rui4,5; Hu, Yahui6; Xiao, Lushan7; Peng, Quanzhou8; Zheng, Zemao1

2023-07-23

10.1007/s12672-023-00755-7

DISCOVER ONCOLOGY   影响因子和分区

1868-8497

2730-6011

Cuproptosis is a recently described copper-dependent cell death pathway. Consequently, there are still few studies on lung adenocarcinoma (LUAD)-related cuproptosis, and we aimed to deepen in this matter. In this study, data from 503 patients with lung cancer from the TCGA-LUAD cohort data collection and 11 LUAD single-cells from GSE131907 as well as from 10 genes associated with cuproptosis were analyzed. The AUCell R package was used to determine the copper-dependent cell death pathway activity for each cell subpopulation, calculate the CellChat score, and display cell communication for each cell subpopulation. The PROGENy score was calculated to show the scores of tumor-related pathways in different cell populations. GO and KEGG analyses were used to calculate pathway activity. Univariate COX and random forest analyses were used to screen prognosis-associated genes and construct models. The ssGSEA and xCell algorithms were used to calculate the immunocyte infiltration score. Based on data from the GDSC database, the drug sensitivity score was calculated using oncoPredict. Finally, in vitro experiments were performed to determine the role of TLE1, the most important gene in the prognostic model. The 11 LUAD single-cell samples were classified into 8 different cell populations, from which epithelial cells showed the highest copper-dependent cell death pathway activity. Epithelial cell subsets were significantly positively correlated with MAKP, hypoxia, and other pathways. In addition, cell subgroup communication showed highly active collagen and APP pathways. Using the Findmark algorithm, differentially expressed genes (DEGs) between epithelial and other cell types were identified. Combined with the bulk data in the TCGA-LUAD database, DEGs were enriched in pathways such as EGFR tyrosine kinase inhibitor resistance, Hippo signaling pathway, and tight junction. Subsequently, we selected 4 genes (out of 112) with prognostic significance, ANKRD29, RHOV, TLE1, and NPAS2, and used them to construct a prognostic model. The high- and low-risk groups, distinguished by the median risk score, showed significantly different prognoses. Finally, we chose TLE1 as a biomarker based on the relative importance score in the prognostic model. In vitro experiments showed that TLE1 promotes tumor proliferation and migration and inhibits apoptosis.

Lung adenocarcinoma Cuproptosis Single cell landscape TLE1 Predictive model

SCI

英语

通讯

Oncology ; Endocrinology & Metabolism

Oncology ; Endocrinology & Metabolism

WOS:001031626900001

SPRINGER

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Resp & Crit Care Med, Guangzhou, Guangdong, Peoples R China
2.Southern Med Univ, Clin Med Sch 1, Guangzhou, Guangdong, Peoples R China
3.Southern Med Univ, Nanfang Hosp, Dept Pediat, Guangzhou, Guangdong, Peoples R China
4.Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China
5.Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou, Guangdong, Peoples R China
6.Southern Med Univ, Nanfang Hosp, Dept Huiqiao Med Ctr, Guangzhou, Guangdong, Peoples R China
7.Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Guangdong, Peoples R China
8.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp,Clin Med Coll 2, Dept Pathol,Affiliated Hosp 1, Shenzhen, Peoples R China

Lin, Weixian,Wang, Jiaren,Ge, Jing,et al. The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma[J]. DISCOVER ONCOLOGY,2023,14(1).

Lin, Weixian.,Wang, Jiaren.,Ge, Jing.,Zhou, Rui.,Hu, Yahui.,...&Zheng, Zemao.(2023).The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma.DISCOVER ONCOLOGY,14(1).

Lin, Weixian,et al."The activity of cuproptosis pathway calculated by AUCell algorithm was employed to construct cuproptosis landscape in lung adenocarcinoma".DISCOVER ONCOLOGY 14.1(2023).