Identification of tumor-infiltrating immune cells and prognostic validation of tumor-infiltrating mast cells in adrenocortical carcinoma: results from bioinformatics and real-world data

Xi Tian; Wenhao Xu; Yuchen Wang; Aihetaimujiang Anwaier; Hongkai Wang; Fangning Wan; Yu Zhu; Dalong Cao; Guohai Shi; Yiping Zhu; Yuanyuan Qu; Hailiang Zhang; Dingwei Ye

doi:10.1080/2162402X.2020.1784529

Identification of tumor-infiltrating immune cells and prognostic validation of tumor-infiltrating mast cells in adrenocortical carcinoma: results from bioinformatics and real-world data

Oncoimmunology. 2020 Jun 23;9(1):1784529. doi: 10.1080/2162402X.2020.1784529.

Authors

Xi Tian^{1

2}, Wenhao Xu^{1

2}, Yuchen Wang^{1

2}, Aihetaimujiang Anwaier^{1

2}, Hongkai Wang^{1

2}, Fangning Wan^{1

2}, Yu Zhu^{1

2}, Dalong Cao^{1

2}, Guohai Shi^{1

2}, Yiping Zhu^{1

2}, Yuanyuan Qu^{1

2}, Hailiang Zhang^{1

2}, Dingwei Ye^{1

2}

Affiliations

¹ Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.

Abstract

Objective: The purpose of this study was to explore the composition of tumor-infiltrating immune cells (TIIC) and prognostic significance of tumor-infiltrating mast cells (TIMC) in adrenocortical carcinoma (ACC).

Methods: The gene expression profiles of ACC were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE90713, GSE12368). The abundance of TIICs in ACC samples was calculated by CIBERSORT algorithm and immunohistochemistry was used to identify mast cells of 39 tumor samples from Fudan University Shanghai Cancer Center (FUSCC). Differentially expressed genes (DEGs) were analyzed by LIMMA package using R software. Survival analysis was analyzed by Kaplan-Meier method and Cox regression models.

Results: The abundance of mast cells (p = .008) was positively correlated with ACC patients' outcome in TCGA cohort and was also positively correlated with both overall survival (p < .05) and progression-free survival (p < .05) in FUSCC cohort. Different TIMC infiltrations showed significant changes in signaling pathways including DNA replication, nuclear chromosome segregation, and meiotic cell cycle process of ACC. In addition, elevated expression of eight hub genes (KIF18A, CDCA8, SKA1, CEP55, BUB1, CDK1, SGOL1, SGOL2) related to the abundance of TIMC in ACC was significantly correlated with the poor prognosis of the patients.

Conclusion: In conclusion, higher TIMC infiltration was positively correlated with ACC patients' outcome in both TCGA and FUSCC cohort. Lower TIMC infiltration and elevated expression of hub genes (KIF18A, CDCA8, SKA1, CEP55, BUB1, CDK1, SGOL1, SGOL2) are markedly correlated with aggressive progression and poor prognosis, which might shed lights on novel targets for treatment strategies.

Keywords: Adrenocortical carcinoma; CIBERSORT; differentially expressed genes; tumor infiltrating immune cells; tumor infiltrating mast cells.

Publication types

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

MeSH terms

Adrenal Cortex Neoplasms* / genetics
Adrenocortical Carcinoma* / genetics
Cell Cycle Proteins
China
Chromosomal Proteins, Non-Histone
Computational Biology
Female
Gene Expression Regulation, Neoplastic
Humans
Kinesins
Male
Mast Cells
Prognosis

Substances

Cell Cycle Proteins
Cep55 protein, human
Chromosomal Proteins, Non-Histone
SKA1 protein, human
KIF18A protein, human
Kinesins

Grants and funding

This work is supported by Grants from the National Key Research and Development Project (No.2019YFC1316000) and National Natural Science Foundation of China (No.81772706 and No.81802525).