Genome and transcriptome profiling of FBXW family in human prostate cancer

Ruoxin Lan; Ben Jin; Yao-Zhong Liu; Kun Zhang; Tianhua Niu; Zongbing You

Genome and transcriptome profiling of FBXW family in human prostate cancer

Am J Clin Exp Urol. 2020 Aug 15;8(4):116-128. eCollection 2020.

Authors

Ruoxin Lan^{1

2}, Ben Jin^{3

1}, Yao-Zhong Liu², Kun Zhang⁴, Tianhua Niu⁵, Zongbing You^{3

1

6

7

8

9}

Affiliations

¹ Department of Structural & Cellular Biology, Tulane University New Orleans, LA, USA.
² Department of Biostatistics and Data Science, Tulane University New Orleans, LA, USA.
³ Southeast Louisiana Veterans Health Care System New Orleans, LA, USA.
⁴ Department of Computer Science and Biostatistics Facility of RCMI Cancer Research Center, Xavier University of Louisiana New Orleans, LA, USA.
⁵ Department of Biochemistry and Molecular Biology, Tulane University New Orleans, LA, USA.
⁶ Department of Orthopaedic Surgery, Tulane University New Orleans, LA, USA.
⁷ Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University New Orleans, LA, USA.
⁸ Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane University New Orleans, LA, USA.
⁹ Tulane Center for Aging, Tulane University New Orleans, LA, USA.

PMID: 32929407
PMCID: PMC7486541

Abstract

F-box and WD repeat domain containing (FBXW) family of E3 ligases has 10 members that ubiquitinate substrate proteins for proteasome-mediated degradation. Publicly archived datasets from The Cancer Genome Atlas (TCGA), Prostate Cancer Transcriptome Atlas (PCTA), and cBioPortal were analyzed for mRNA expression and genetic alterations of 10 FBXW genes. We found that FBXW7 mRNA expression was significantly decreased in primary prostate cancers compared to normal prostate tissues, whereas mRNA expression of FBXW8-10 was significantly increased in primary prostate cancers compared to normal prostate tissues. FBXW7 mRNA expression was also significantly decreased in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and uterine corpus endometrial carcinoma. In contrast, FBXW7 mRNA expression was significantly increased in cholangiocarcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pheochromocytoma and paraganglioma, and thyroid carcinoma. Compared to normal tissues, FBXW5 mRNA expression was significantly increased in breast invasive carcinoma, cholangiocarcinoma, kidney chromophobe, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, thyroid carcinoma, and uterine corpus endometrial carcinoma, whereas FBXW5 mRNA expression was only significantly decreased in colon adenocarcinoma. There were not any significant differences in gene copy number gains, losses, or gene simple somatic mutations between primary prostate cancers and normal prostate tissues. The mRNA expression levels of FBXW5, 7, 8, 9, and 12 were significantly higher in metastatic castration-resistant prostate cancers (mCRPCs) than primary prostate cancers, whereas mRNA expression levels of FBXW1 and 4 were significantly lower in mCRPCs than primary prostate cancers. All 10 FBXW genes had significantly more overall gene alterations including gene amplifications in mCRPCs than primary prostate cancers. FBXW5 and 7 had significantly more gene deep deletions in mCRPCs than primary prostate cancers and FBXW7 had significantly more gene missense mutations in mCRPCs than primary prostate cancers. Our findings suggest that different FBXW genes have differential mRNA expression in prostate cancer and other cancer types and their gene amplifications are significantly more in mCRPCs than primary prostate cancers. FBXW7 mRNA expression is consistently decreased in primary prostate cancers compared to normal prostate tissues.

Keywords: FBXW; Prostate cancer; gene amplification; mCRPC.

Abstract

Grants and funding