Open AccessCharacterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel‐like factors in prostate cancer
Author(s) -
Meng Jialin,
Lu Xiaofan,
Zhou Yujie,
Zhang Meng,
Gao Lei,
Gao Shenglin,
Yan Fangrong,
Liang Chaozhao
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15242
Subject(s) - oncology , prostate cancer , immunotherapy , medicine , proportional hazards model , cohort , cancer research , cancer , biology
At present, the overall genetic and epigenetic effects of Krüppel‐like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score ( P = .009), pathology T stage ( P = .006), KLF3 ( P = .034), KLF5 ( P = .002) and KLF7 ( P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort ( P < .001) and validated in the MSKCC ( P < .001) and GSE116918 cohorts ( P = .006). Demethylation of KLF5 by 5‐azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF‐F were more likely to respond to immunotherapy ( P < .001) and bicalutamide ( P < .001). In summary, we found that the KLFs and clinical feature‐based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management.