Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers

Wei Han; Chun-Tao Shi; Jun Ma; Hua Chen; Qi-Xiang Shao; Xiao-Jiao Gao; Ying Zhou; Jing-Feng Gu; Hao-Nan Wang

doi:10.1016/j.heliyon.2022.e10786

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers

Heliyon. 2022 Sep 28;8(10):e10786. doi: 10.1016/j.heliyon.2022.e10786. eCollection 2022 Oct.

Authors

Wei Han^{1

2}, Chun-Tao Shi³, Jun Ma⁴, Hua Chen¹, Qi-Xiang Shao⁵, Xiao-Jiao Gao⁶, Ying Zhou³, Jing-Feng Gu⁶, Hao-Nan Wang⁷

Affiliations

¹ Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, PR China.
² Department of General Surgery, Kunshan Maternity and Child Care Hospital, Kunshan Jiangsu, 215300, PR China.
³ Department of General Surgery, Wuxi Xishan People's Hospital, Wuxi Jiangsu, 214000, PR China.
⁴ Department of Urology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Jiangsu, 215300, PR China.
⁵ Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang Jiangsu, 212013, PR China.
⁶ Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, PR China.
⁷ Oncology Department, Wuxi Fifth People's Hospital, Wuxi Jiangsu, 214000, PR China.

Abstract

Background: X-inactive specific transcript (XIST), it has been found, is abnormal expression in various neoplasms. This work aims to explore its potential molecular mechanisms and prognostic roles in types of malignancies.

Methods: This research comprehensively investigated XIST transcription across cancers from Oncomine, TIMER 2.0 and GEPIA2. Correlations of XIST expression with prognosis, miRNAs, interacting protens, immune infiltrates, checkpoint markers, mutations of tumor-associated genes and promoter methylation were also analyzed by public databases. In addition, 98 BRCA samples were collected to investigate XIST expression and evaluate its clinicopathological value.

Results: In public databases, compared to normal tissues, XIST was lower in BRCA, CESC, COAD and so on, but increased in KIRC and PRAD. Databases also showed that XIST was a good indicator of prognosis in BRCA, COAD and so on, but a bad one in KIRC, KIRP and so on. From starBase, we found 29 proteins interacting with XIST, and identified 4 miRNAs which might be sponged by XIST in cancers. Furthermore, XIST was linked with immune infiltration, especially T cell CD4+, and was related to over 20 immune checkpoint markers. Moreover, several tumor-associated gene mutations and promoter methylation were negatively related to its expression. In addition, IHC showed that XIST in BRCA was obviously lower in comparison of normal tissues and was negatively related to lymph node invasion and TNM stage.

Conclusion: In summary, abnormal expression of XIST influenced prognosis, miRNAs and immune infiltration across cancers, especially BRCA.

Keywords: Pan-cancer analysis; Prognosis; Tumor immunity; XIST; ceRNA; miRNA.