Author:
Feng Dechao,Wang Jie,Shi Xu,Li Dengxiong,Wei Wuran,Han Ping
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.
Funder
National Key Research and Development Program of China
Publisher
Springer Science and Business Media LLC
Reference108 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71(3):209–49.
2. Yu J, Li T, Zhu J. Gene therapy strategies targeting aging-related diseases. Aging Dis. 2023;14(2):398–417.
3. Shih KW, Chen WC, Chang CH, Tai TE, Wu JC, Huang AC, et al. Non-muscular invasive bladder cancer: re-envisioning therapeutic journey from traditional to regenerative interventions. Aging Dis. 2021;12(3):868–85.
4. Schwartz AG. Dehydroepiandrosterone, cancer, and aging. Aging Dis. 2022;13(2):423–32.
5. Feng D, Shi X, You J, Xiong Q, Zhu W, Wei Q, et al. A cellular senescence-related gene prognostic index for biochemical recurrence and drug resistance in patients with prostate cancer. Am J Cancer Res. 2022;12(8):3811–28.
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