Researchers are developing a prognostic hypoxia gene signature for patients with localized prostate cancer that could predict biochemical failure and metastasis, according to data (abstract 5) presented at the 2018 Genitourinary Cancers Symposium, held February 8–10 in San Francisco.
The 28-gene signature was prognostic among both patients treated with prostatectomy and those treated with radiotherapy, reported lead study author Ananya Choudhury, MA, PhD, MRCP, FRCR, of the Christie NHS Foundation Trust and University of Manchester in the United Kingdom.
“The biomarker consistently predicts biochemical failure and metastasis for prostate cancer patients with localized disease,” Dr. Choudhury said.
Ninety percent of patients with prostate cancer are diagnosed with localized carcinomas, a disease state with “marked and heterogeneous” hypoxia, increasing metastatic potential and radiotherapy resistance, Dr. Choudhury noted. There currently exists no clinically validated test for selecting patients most likely to benefit from hypoxia modification.
Using four prostate cancer cell lines (PNT2-C2, LNCaP, DU145, and PC-3), the researchers identified genes with expression regulated by hypoxia to develop a 28-loci hypoxia-regulated gene signature.
To validate the signature, they then tested whether or not it predicted biochemical recurrence (BCR)-free survival probability using data from six patient cohorts, including the GSE54460, GSE21032, GSE79957, GSE62116, CPC-GENE, and Cambridge prostatectomy cohorts. The signature was subsequently validated using adjuvant radiotherapy and radical radiotherapy patient cohorts (GSE72291 and the Belfast).
For all of those cohorts, hypoxia gene signature scores were significantly or near-significantly associated with poor probability of BCR-free survival (Ps = .0009 to .05). In multivariate analyses of data from the salvage radiotherapy cohort that also included Gleason scores, pretreatment PSA levels, and tumor T stage, the signature was significantly associated with risk of metastasis.
Additional research is needed, Dr. Choudhury said.