Comprehensive RNA-Seq Reveals Molecular Changes in Kidney Malignancy Among People Living with HIV

Abstract

BackgroundMalignancy of the kidney is a rapidly progressive kidney disease and a major source of morbidity and mortality among people living with HIV (PLWH). Patients with HIV-associated kidey cancer experience higher cancer-specific mortality than the general population, and its mechanism remains poorly understood. MethodsTo heighten the awareness of kidney malignancy in patients with HIV infection to facilitate the early diagnosis of kidney cancer, we identified 2460 protein-coding transcripts in HIV-associated kidney cancer using comprehensive RNA sequencing (RNA-seq). ResultsKISS1R, CAIX, and NPTX2 mRNA expression levels were specifically increased in HIV-associated kidney cancer, and 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 16 of 18 kidney malignant cases among PLWH exhibited positive staining for KISS1R and CAIX. ConclusionPathway analysis of the differentially expressed mRNAs in HIV-associated kidney cancer revealed that several key pathways were involved, including voltage-gated chloride channel activity, distal tubule development, collecting duct development, fructose metabolic processes, and negative regulation of lipase activity. The identified molecular changes in kidney malignancy may offer a helpful explanation for cancer progression and open up new therapeutic avenues that may decrease mortality after a cancer diagnosis among PLWH.