Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Juan Bao; Jianqing Ye; Jingjing Xu; Shanshan Liu; Lin Wang; Zehuan Li; Qiuyue Li; Feng Liu; Xiaomeng He; Heng Zou; Yanling Feng; Christopher Corpe; Xiaoyan Zhang; Jianqing Xu; Tongyu Zhu; Jin Wang

doi:10.1016/j.omtn.2022.06.002

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Mol Ther Nucleic Acids. 2022 Jun 14:29:91-101. doi: 10.1016/j.omtn.2022.06.002. eCollection 2022 Sep 13.

Authors

Juan Bao¹, Jianqing Ye^{2

3}, Jingjing Xu¹, Shanshan Liu¹, Lin Wang¹, Zehuan Li⁴, Qiuyue Li¹, Feng Liu¹, Xiaomeng He¹, Heng Zou¹, Yanling Feng¹, Christopher Corpe⁵, Xiaoyan Zhang¹, Jianqing Xu¹, Tongyu Zhu¹, Jin Wang¹

Affiliations

¹ Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Jinshan District, Shanghai 201508, China.
² Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai, China.
³ Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai, China.
⁴ Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ King's College London, London, Nutritional Science Department, 150 Stamford Street, Waterloo, London SE19NH, UK.

Abstract

To heighten the awareness of kidney malignancy in patients with HIV infection to facilitate the early diagnosis of kidney cancer, the differentially expressed mRNAs were analyzed in this malignant tumor using RNA sequencing. We identified 2,962 protein-coding transcripts in HIV-associated kidney cancer. KISS1R, CAIX, and NPTX2 mRNA expression levels were specifically increased in HIV-associated kidney cancer while UMOD and TMEM213 mRNA were decreased in most cases based on real-time PCR analyses. These findings were similar to those noted for the general population with renal cell carcinoma. Immunohistochemical staining analysis also showed that a total of 18 malignant kidney cases among the people living with HIV (PLWH) exhibited positive staining for KISS1R and CAIX. Pathway analysis of the differentially expressed mRNAs in HIV-associated kidney cancer revealed that several key pathways were involved, including vascular endothelial growth factor-activated receptor activity, IgG binding, and lipopolysaccharide receptor activity. Altogether, our findings reveal the identified molecular changes in kidney malignancy, which may offer a helpful explanation for cancer progression and open up new therapeutic avenues that may decrease mortality after a cancer diagnosis among PLWH.

Keywords: CAIX; HIV infection; HIV-associated kidney cancer; KISS1R; NPTX2; RNA-seq; biomarker; kidney malignancy.