Critical Evaluation of Transcripts and Long Noncoding RNA Expression Levels in Prostate Cancer Following Radical Prostatectomy

Pathobiology. 2023;90(6):400-408. doi: 10.1159/000531175. Epub 2023 Jul 18.

Abstract

Introduction: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk.

Methods: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status.

Results: Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression.

Conclusion: While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.

Keywords: Biochemical recurrence; Biochemical recurrence-free survival; Gleason score; Long noncoding RNA; Prostate cancer.

MeSH terms

  • Humans
  • Male
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / surgery
  • Prostate / pathology
  • Prostate-Specific Antigen
  • Prostatectomy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / surgery
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Prostate-Specific Antigen

Grants and funding

This study was financially supported by the OSKK (Ostschweizerische Stiftung für klinische Krebsforschung) and STIFTUP in St. Gallen/Switzerland. The two foundations of St. Gallen provided money for reagents and study performance. Both play no role in the study performance nor interpretation.