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

Abstract

Background: 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. Aim: This study explores the application of SRARP as a novel biomarker in malignancies of multiple tissue origins using the analysis of large genomic datasets. Methods and results: 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. Conclusion: This study suggests that the SRARP inactivation presents a robust biomarker in predicting molecular and clinicopathological features, and treatment response in malignancies.

Machine learning-driven exploration of drug therapies for triple-negative breast cancer treatment

“…Knockdown of SETD7 inhibited cancer cell proliferation, induced G1/S cell cycle arrest, and increased apoptosis. Along with SETD7, we chose two other biomarkers known as SRARP and YIPF5 (Suárez-Arroyo et al, 2016;Naderi, 2020) (Supplementary Figures S29, S30; Table 4). SRARP, which is found on chromosome 1p36, has recently been discovered as a new corepressor of the androgen receptor (AR).…”

“…SRARP, which is found on chromosome 1p36, has recently been discovered as a new corepressor of the androgen receptor (AR). In breast cancer cell lines, primary breast tumors, and metastatic breast cancer, SRARP has been shown to be highly co-expressed with AR (Naderi, 2020). SRARP also has a fairly advanced countenance in breast tumors that are estrogen receptor-positive (ER+), lower grade, and lobular histology (Su et al, 2012;Naderi, 2018).…”