SRSF‐1 and microvessel density immunohistochemical analysis by semi‐automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study)

Objective To study the association between insulin receptors (isoforms α and β), insulin growth factor‐1 (IGF1) and serine/arginine splicing factor 1 (SRSF‐1) in patients with prostate cancer (PC) and diabetes. Materials and Methods We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor‐α and ‐β, IGF1 (IGF1‐R), Ki‐67, and prostate specific membrane antigen (PSMA) expression using validated score. Results The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF‐1 expression was associated with AR (odds ratio [OR]: 1.66), PSMA (OR: 2.13), Ki‐67 (OR: 5.99), insulin receptor (IR)‐α (OR: 2.38), IR‐β (OR: 3.48), IGF1‐R (OR: 1.53), and microvascular density (MVD) was associated with PSMA (OR: 3.44), Ki‐67 (OR: 2.23), IR‐α (OR: 2.91), IR‐β (OR: 3.02), IGF1‐R (OR: 2.95), and SRSF‐1 (OR: 2.21). In the sub cohort of PC patients, we found that SRSF‐1 expression was associated with AR (OR: 2.34), Ki‐67 (OR: 6.77), IR‐α (OR: 2.7), and MVD (OR: 1.98). At the Kaplan–Meier analysis, SRSF‐1+ patients had worse 5‐ and 9‐year biochemical recurrence (36% and 6%) respect to SRSF‐1− (67% and 7%; p < .01) and similarly MVD+ patients (44% and 7%) respect to MVD− (64% and 8%; p < .01). Restricting the analysis only in patients with PC and diabetes, we found that SRSF‐1+ was associated with Ki‐67+ (OR: 8.75; p < .05) and MVD+ (OR: 7.5; p < .05). Conclusions PC exhibits widespread heterogeneity in protein expression. In particular, the expressions of the SRSF‐1 protein and of the MVD are associated with a worse prognosis and in particular with a greater cell proliferation. These results, although preliminary, may offer new future scientific insights with the aim of highlighting possible genetic alterations linked to a greater expression of SRSF‐1 and associated with a worse prognosis.