Prognostic Model Predicts Prostate Cancer Progression
Researchers at Sichuan Cancer Hospital published a peripheral blood mRNA-based prognostic model on October 14, 2026, in Frontiers in Oncology to predict when metastatic hormone-sensitive prostate cancer advances to castration-resistant disease. Approximately 35% of patients with metastatic hormone-sensitive prostate cancer experience this progression, highlighting limitations in relying on prostate-specific antigen testing alone as a monitoring biomarker.
Patient Screening and Cohort Development
Investigators screened 230 patients between February 1, 2024, and February 1, 2025, enrolling 157 individuals into the study. Eligible participants had de novo metastatic hormone-sensitive prostate cancer, at least one measurable lesion under RECIST 1.1 criteria, and an Eastern Cooperative Oncology Group performance status of 2 or lower. These patients received androgen deprivation therapy combined with an androgen receptor pathway inhibitor, with or without docetaxel. The research team split the enrolled patients 7:3 into development and validation cohorts, with 147 total patients completing follow-up.
Biomarker Discovery and SLC6A8 Inhibition
Single-cell transcriptomic data analysis from the GSE288878 dataset identified genes associated with metastatic castration-resistant prostate cancer. Intersecting these differentially expressed genes with the prospective cohort yielded five candidate genes: SLC25A39, GRB10, SELENBP1, SLC6A8, and YBX3. Elastic net-regularized Cox regression selected three final genes for the model. Elevated SLC6A8 expression in peripheral blood and tumor tissue emerged as an independent risk factor for shorter progression-free survival. In C4-2B cancer cells, the SLC6A8 inhibitor ompenaclid suppressed cell proliferation, promoted apoptosis, and reduced glycolytic metabolites including lactic acid, pyruvic acid, and fructose-1,6-bisphosphate.
Treatment Intensification and Future Validation
Shengke Yang noted that the transcriptomic signature provides a framework for precision risk stratification in equivocal cases, such as oligometastatic bone disease or borderline prostate-specific antigen levels. First, for patients in whom clinical risk is equivocal—such as those with oligometastatic bone disease or borderline [prostate-specific antigen (PSA)] levels—the signature could guide intensification with triplet therapy or earlier combination with local treatment (eg, metastasis-directed radiotherapy) if the molecular profile predicts rapid progression,
Yang wrote. Investigators plan a prospective multicenter validation study across three to five tertiary centers in China to address single-center limitations and exclusively East Asian population constraints.
Frequently Asked Questions
What primary endpoint did the prognostic model evaluate?
The primary end point of the study was metastatic castration-resistant prostate cancer–free survival, assessed at a median follow-up of 611 days where 54 patients had progressed.
How many patients completed the study follow-up?
A total of 147 patients completed follow-up out of the 157 enrolled participants, split into 103 patients in the development cohort and 44 in the validation cohort.
What specific metabolic pathways does SLC6A8 affect in cancer cells?
Elevated SLC6A8 promotes prostate cancer progression through enhanced glycolysis, and its pharmacological inhibition downregulates glycolysis-associated genes such as HK2, PFKP, and ALDH1B1.
Related reading