Steroid receptor-associated and regulated protein is a biomarker in predicting the clinical outcome and treatment response in malignancies.

Abstract

Steroid receptor-associated and regulated protein (SRARP) has recently been identified as a novel tumor suppressor in malignancies of multiple tissue origins. SRARP is located on chromosome 1p36.13 and is widely inactivated by deletions and epigenetic silencing in malignancies. Therefore, additional studies are required to explore SRARP as a potential cancer biomarker. This study explores the application of SRARP as a novel biomarker in malignancies of multiple tissue origins using the analysis of large genomic datasets. A comprehensive genomic analysis of large cancer datasets was carried out to examine the association of SRARP expression and copy-number with molecular and clinical features in malignancies of multiple tissue origins. This study demonstrated that SRARP under-expression and copy-number loss are strongly associated with the loss of other tumor suppressors such as TP53 and NF1 mutations and oncogenic gains, including N-MYC amplification and ERG rearrangement, suggesting that SRARP inactivation is associated with wider genomic instability in malignancies. Importantly, SRARP under-expression and copy-number loss are strong predictors of poor clinical and/or pathological features in breast, colorectal, lung, prostate, gastric, endometrial, cervical, brain, ovarian, bladder, thyroid, and hepatocellular cancers as well as neuroblastoma, uveal melanoma, and acute myeloid leukemia with highly significant odds ratios. Finally, higher SRARP expression and copy-number predict a better response to several cancer drugs. This study suggests that the SRARP inactivation presents a robust biomarker in predicting molecular and clinicopathological features, and treatment response in malignancies.