Whole blood mRNA in prostate cancer reveals a four-gene androgen regulated panel

Abstract

Due to increased sensitivity, the expression of circulating nucleotides is rapidly gaining popularity in cancer diagnosis. Whole blood mRNA has been used in studies on a number of cancers, most notably two separate studies that used whole blood mRNA to define non-overlapping signatures of prostate cancer that has become castration independent. Prostate cancer is known to rely on androgens for initial growth, and there is increasing evidence on the importance of the androgen axis in advanced disease. Using whole blood mRNA samples from patients with prostate cancer, we have identified the four-gene panel of FAM129A, MME, KRT7 and SOD2 in circulating mRNA that are differentially expressed in a discovery cohort of metastatic samples. Validation of these genes at the mRNA and protein level was undertaken in additional cohorts defined by risk of relapse following surgery and hormone status. All the four genes were downregulated at the mRNA level in the circulation and in primary tissue, but this was not always reflected in tissue protein expression. MME demonstrated significant differences in the hormone cohorts, whereas FAM129A is downregulated at the mRNA level but is raised at the protein level in tumours. Using published ChIP-seq data, we have demonstrated that this may be due to AR binding at the FAM129A and MME loci in multiple cell lines. These data suggest that whole blood mRNA of androgen-regulated genes has the potential to be used for diagnosis and monitoring of prostate cancer.

The epigenetic factor BORIS (CTCFL) controls the androgen receptor regulatory network in ovarian cancer

“…Because the ovary is also responsible for the synthesis of AR, it would be of great importance the search for biomarkers related to this protein 28–30 . Interestingly, our results from KPM demonstrated that BORIS is partly responsible for the regulation of AR gene expression, and in turn, AR establishes a gene regulatory network with genes such as FN1 , CD97 , and FAM129A , which are related with poor prognosis, chemoresistance, and metastasis in several cancers, including OC 31–33 . Previous studies are limited to the identification of possible target genes by evaluating changes in gene expression by increasing or decreasing BORIS levels; 5,6,11,19,34 however, our de novo pathway enrichment analysis allowed us to perform a novel selection (based on hundreds of experimental data available in public databases) of potential genes relevant in cancer, which are closely related through AR and BORIS.…”

FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner

“…Several groups have showed that FAM129A is overexpressed in several cancer subtypes (Matsumoto et al 2006, Ito et al 2009, Thomas et al 2016. Additionally, the human protein atlas analysis, which evaluated tissue array based on immunohistochemistry for numerous proteins in normal tissues and over 200 tumor subtypes from 20 different cancer and cell lines, demonstrated that FAM129A is overexpressed in colorectal cancer, breast…”

“…Among these markers, FAM129A (aliases C1orf24, NIBAN and GIG39) has been reported to be overexpressed in various human cancer, strengthening its pathogenic relevance (Majima et al 2000, Adachi et al 2004, Matsumoto et al 2006, Ito et al 2009, Thomas et al 2016. FAM129A (family with sequence similarity 129 member A) gene is mapped on chromosome 1q25.3 and codifies a protein predominantly expressed in the cytoplasm.…”

Characterization of HMGB1/2 Interactome in Prostate Cancer by Yeast Two Hybrid Approach: Potential Pathobiological Implications

“…Indeed, FLNA has already been proposed in a clinical validated PCa biomarker panel in serum [74]. PSMA7 was also proposed as a PCa biomarker [55], and KRT7 is included in a whole blood mRNA 4-gene androgen regulated panel for PCa diagnosis [33]. Considering the relative expression levels of our HMGB1 and HMGB2 interactome targets in noncancerous cells or in blood of health subjects differ quite notably (Figure 7), one might anticipate that more sensitive analyses could be carried out using as biomarkers those proteins that are usually lowly expressed in noncancerous cells; thus, their levels are also low in the blood of healthy individuals.…”