Dataset Information

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

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.

SUBMITTER: Feng D

PROVIDER: S-EPMC10182623 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

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

Feng Dechao D Wang Jie J Shi Xu X Li Dengxiong D Wei Wuran W Han Ping P

European journal of medical research 20230513 1

<h4>Background</h4>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.<h4>Methods</h4>Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages.<h4>Resul ...[more]

PMID: 37179366

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Project description:BackgroundtRNA-derived RNA fragments (tRFs) are a novel class of small ncRNA that are derived from precursor or mature tRNAs. Recently, the general relevance of their roles and clinical values in tumorigenesis, metastasis, and recurrence have been increasingly highlighted. However, there has been no specific systematic study to elucidate any potential clinical significance for these tRFs in prostate adenocarcinoma (PRAD), one of the most common and malignant cancers that threatens male health worldwide. Here, we investigate the clinical value of 5'-tRFs in PRAD.MethodsSmall RNA sequencing data were analyzed to discover new 5'-tRFs biomarkers for PRAD. Machine learning algorithms were used to identify 5'-tRF classifiers to distinguish PRAD tumors from normal tissues. LASSO and Cox regression analyses were used to construct 5'-tRF prognostic predictive models. NMF and consensus clustering analyses were performed on 5'-tRF profiles to identify molecular subtypes of PRAD.ResultsThe overall levels of 5'-tRFs were significantly upregulated in the PRAD tumor samples compared to their adjacent normal samples. tRF classifiers composed of 13 5'-tRFs achieved AUC values as high as 0.963, showing high sensitivity and specificity in distinguishing PRAD tumors from normal samples. Multiple 5'-tRFs were identified as being associated with the PRAD prognosis. The tRF score, defined by a set of eight 5'-tRFs, was highly predictive of survival in PRAD patients. The combination of tRF and Gleason scores showed a significantly better performance than the Gleason score alone, suggesting that 5'-tRFs can offer PRAD patients additional and improved prognostic information. Four molecular subtypes of the PRAD tumor were identified based on their 5'-tRF expression profiles. Genetically, these 5'-tRFs PRAD tumor subtypes exhibited distinct genomic landscapes in tumor cells. Clinically, they showed marked differences in survival and clinicopathological features.Conclusions5'-tRFs are potential clinical biomarkers for the diagnosis, prognosis, and classification of tumor subtypes on a molecular level. These can help clinicians formulate personalized treatment plans for PRAD patients and may have similar potential applications for other disease types.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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