Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer

Li, Yuezheng; Wang, Haoyu; Pan, Yang; Wang, Shangren; Zhang, Zhexin; Zhou, Hang; Xu, Mingming; Liu, Xiaoqiang

doi:10.3389/fendo.2023.1125299

Cited by 4 publications

(2 citation statements)

References 63 publications

(70 reference statements)

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“…In total 18 genes were signi cantly (p < 0.05) related with survival of patients with PCa. KCNQ1, M2T2A, SORBS1, MIR204, RNF207, and QRFP were reported in other studies as prognostic biomarkers (24)(25)(26)(27)(28)(29)(30). Other genes considered as novel prognostic biomarkers for further evaluation.…”

Section: Discussionmentioning

confidence: 88%

The potential prognostic value of Cartilage acidic protein 1 and secretoglobin family 1D member 1 in prostate cancer

Sokhangouy,

Asadnia,

Negahbanzaferanloo

et al. 2023

Preprint

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Background Prostate cancer is a prevalent malignancy with a broad range of clinical outcomes, necessitating improved prognostic biomarkers for precise patient stratification and personalized treatment. This study leverages machine learning techniques to identify and validate novel prognostic biomarkers using DNAseq and RNAseq data for prostate cancer. Methods Whole genome sequencing and gene expression profiling in patients were used from TCGA to identify DEGs and genetic alterations. Next, deep learning was utilized to determine key genes. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the involved biological process and pathways. Survival analysis of patients with prostate cancer with reference on dysregulated genes was conducted using Cox regression and Kaplan-Meier analysis. The STRING database was used to build a protein-protein interaction (PPI) network. Moreover, candidate genes were subjected to machine learning -based analysis and the Receiver operating characteristic (ROC) curve. Results We identified a total of 609 DEGs in patients, of which 358 were downregulated and 251 were upregulated. Deep learning results identified 20 genes, and these were combined with the analysis of DNA-seq. Survival analysis of patients with prostatic cancer showed that dysregulated expression of ASB12, BLOC1S1, CRTAC1, KCNQ1, KISS1, M2T2A, RNF207, SCGB1D1, SLC13A2, SORBS1, TGFBR3, WSCD2, ANFKFY1, CRYBA4, MIR204, QRFP, SNX15, and YWHAH genes were related with a poor clinical prognosis. The combio-ROC curve analysis reveals ed that TGFRB3, SCGB1D1 and CRTAC1 were potential diagnostic biomarkers with a great higher sensitivity and AUC than currently available biomarkers. Also, the combination of SCGB1D1 and CRTAC1 demonstrated the greatest accuracy, sensitivity, and specificity towards diagnostic applications. The potential value of these markers was validated in six other datasets. Conclusion Our findings demonstrated the potential value of SCGB1D1 and CRTAC1 as novel biomarkers and therapeutic targets in prostate cancer which had a higher AUC, sensitivity, and specificity compared to PSA, indicating further functional investigations on the potential value of emerging markers in prostate cancer.

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Section: Discussionmentioning

confidence: 88%

The potential prognostic value of Cartilage acidic protein 1 and secretoglobin family 1D member 1 in prostate cancer

Sokhangouy,

Asadnia,

Negahbanzaferanloo

et al. 2023

Preprint

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“…Although BIC — a first-line anti-androgen medication for PCa 40 — is therapeutically effective, resistance to the drug develops readily. One possible BIC-resistance mechanism is the overamplification of the androgen receptor (AR) gene.…”

Section: Discussionmentioning

confidence: 99%

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Zhang,

Yu,

Bai

et al. 2024

J. Cancer

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Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

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Five genes identified as prognostic markers for colorectal cancer through the integration of genome-wide association study and expression quantitative trait loci data

Zhang,

Huang,

Niu

et al. 2024

Personalized Medicine

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Background: Colorectal cancer (CRC) is a prominent form of cancer globally, ranking second in terms of prevalence and serving as a leading cause of cancer-related deaths, but the underlying biological interpretation remains largely unknown. Methods: We used the summary data-based Mendelian randomization method to integrate CRC genome-wide association studies (ncase = 7062; ncontrol = 195,745) and expression quantitative trait loci summary data in peripheral whole blood (Consortium for Architecture of Gene Expression: n = 2765; Genotype-Tissue Expression [v8]: n = 755) and colon tissue (colon-transverse: n = 406; colon-sigmoid: n = 373) and identified related genes. Results: Genes ABTB1, CYP21A2, NLRP1, PHKG1 and PIP5K1C have emerged as significant prognostic markers for CRC patient survival. Functional analysis revealed their involvement in cancer cell migration and invasion mechanisms, providing valuable insights for the development of future anti-CRC drugs. Conclusion: We successfully identified five CRC risk genes, providing new insights and research directions for the effective mechanisms of CRC.

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Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer

Cited by 4 publications

References 63 publications

The potential prognostic value of Cartilage acidic protein 1 and secretoglobin family 1D member 1 in prostate cancer

The potential prognostic value of Cartilage acidic protein 1 and secretoglobin family 1D member 1 in prostate cancer

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Five genes identified as prognostic markers for colorectal cancer through the integration of genome-wide association study and expression quantitative trait loci data

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