Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Abstract

Abstract Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p < 0.001), which was externally validated in other three cohorts. The top ten mutation genes between stiff and soft subtypes were DNAH, NYNRIN, PTCHD4, WNK1, ARFGEF1, HRAS, ARHGEF2, MYOM1, ITGB6 and CPS1. E2F targets, base excision repair and notch signaling pathway were highly enriched in stiff subtype. Stiff subtype had significantly higher TMB and T cells follicular helper levels than soft subtype, as well as CTLA4, CD276, CD47 and TNFRSF25. Conclusions From the perspective of cell membrane tension, we found that stiff and soft tumor subtypes were closely associated with BCR-free survival for PCa patients, which might be important for the future research in the field of PCa.

Keywords

• Prostate cancer
• Biochemical recurrence
• Membrane tension
• Nonnegative matrix factorization