Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer

Ai, Jun; Zhang, Baotong; Zhang, Zhiqian; Hu, Hailiang; Dong, Jin‐Tang

doi:10.3390/cancers13040917

Cited by 22 publications

(15 citation statements)

References 94 publications

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“…For example, the SPP1 gene was identified as an extracellular matrix signature, which was remarkably up-regulated in mCRPC and may be a novel therapeutic target for mCRPC patients ( Pang et al, 2019 ). Based on the transcriptome profiles, a CRPC-derived prognosis signature was developed to predict the recurrence-free survival, overall survival, and metastasis-free survival in PCa patients ( A et al, 2021 ). However, markers currently available to predict the progression related to castration resistance in PCa patients are still lacking.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer

Shi

et al. 2022

Front. Genet.

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Background: The emergence of castration resistance is fatal for patients with prostate cancer (PCa); however, there is still a lack of effective means to detect the early progression. In this study, a novel combined nomogram was established to predict the risk of progression related to castration resistance.Methods: The castration-resistant prostate cancer (CRPC)-related differentially expressed genes (DEGs) were identified by R packages “limma” and “WGCNA” in GSE35988-GPL6480 and GSE70768-GPL10558, respectively. Relationships between DEGs and progression-free interval (PFI) were analyzed using the Kaplan–Meier method in TCGA PCa patients. A multigene signature was built by lasso-penalized Cox regression analysis, and assessed by the receiver operator characteristic (ROC) curve and Kaplan–Meier curve. Finally, the univariate and multivariate Cox regression analyses were used to establish a combined nomogram. The prognostic value of the nomogram was validated by concordance index (C-index), calibration plots, ROC curve, and decision curve analysis (DCA).Results: 15 CRPC-related DEGs were identified finally, of which 13 genes were significantly associated with PFI and used as the candidate genes for modeling. A two-gene (KIFC2 and BCAS1) signature was built to predict the risk of progression. The ROC curve indicated that 5-year area under curve (AUC) in the training, testing, and whole TCGA dataset was 0.722, 0.739, and 0.731, respectively. Patients with high-risk scores were significantly associated with poorer PFI (p < 0.0001). A novel combined nomogram was successfully established for individualized prediction integrating with T stage, Gleason score, and risk score. While the 1-year, 3-year, and 5-year AUC were 0.76, 0.761, and 0.762, respectively, the good prognostic value of the nomogram was also validated by the C-index (0.734), calibration plots, and DCA.Conclusion: The combined nomogram can be used to predict the individualized risk of progression related to castration resistance for PCa patients and has been preliminarily verified to have good predictive ability.

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Section: Introductionmentioning

confidence: 99%

Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer

Shi

et al. 2022

Front. Genet.

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“…Interestingly, expression of NKTR is regulated by IL-2 through alternate splicing [ 29 ]. LMO7 has recently been implicated in cancer, showing it promotes pancreatic cancer progression, but is associated with better prognosis in prostate cancer [ 30 ], p. 7, [ 31 ]. The events that showed the most increased PSI in the tumor were those in TPM1 (member of the tropomyosin family), COL5A1 (encodes alpha chain for fibrillar collagen), DEPDC5 (inhibits mTORC1 pathway), PIFO (involved in cilia formation), SREK1 (SR splicing protein) and SNRPD1 (part of the spliceosome).…”

Section: Resultsmentioning

confidence: 99%

CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort

Levesque

Roy

Salazar

2021

Life

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CXCR3 is a chemokine receptor with two well-characterized isoforms that have unique, context-dependent roles: CXCR3-A and CXCR3-B, which are produced through alternative 3′ splice site selection (A3SS). RNA-seq data from The Cancer Genome Atlas (TCGA) were used to correlate CXCR3 expression with breast cancer progression. This analysis revealed significant CXCR3 expression patterns associated with survival and differential expression between the tumor and adjacent normal tissue. TCGA data were used to estimate abundance of immune cells in breast cancer, which demonstrated the association of CXCR3 with immune infiltration, particularly in the triple-negative subtype. Given the importance of A3SS in CXCR3, genome-wide analysis of A3SS events was performed to identify events that were differentially spliced between breast cancer tissue and adjacent normal tissue. A total of 481 splicing events in 424 genes were found to be differentially spliced. The parent genes of differentially spliced events were enriched in RNA processing and splicing functions, indicating an underappreciated role of A3SS in the integrated splicing network of breast cancer. These results further validated the role of CXCR3 in immune infiltration of tumors, while raising questions about the role of A3SS splicing.

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“…This also applies to ALDH2 expression alone as its higher expression correlated with a better recurrence-free survival and discriminated from CRPC. Furthermore, its elevated expression was shown as part of a six gene prognostic signature for overall and metastasis-free survival [ 29 ]. All these findings hint at a tumor-suppressive function of ALDH2.…”

Section: Aldh2mentioning

confidence: 99%

The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

Püschel

Dubrovska

Gorodetska

2021

Cancers

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Cancer stem cells (CSCs) are the only tumor cells possessing self-renewal and differentiation properties, making them an engine of tumor progression and a source of tumor regrowth after treatment. Conventional therapies eliminate most non-CSCs, while CSCs often remain radiation and drug resistant, leading to tumor relapse and metastases. Thus, targeting CSCs might be a powerful tool to overcome tumor resistance and increase the efficiency of current cancer treatment strategies. The identification and isolation of the CSC population based on its high aldehyde dehydrogenase activity (ALDH) is widely accepted for prostate cancer (PCa) and many other solid tumors. In PCa, several ALDH genes contribute to the ALDH activity, which can be measured in the enzymatic assay by converting 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) aminoacetaldehyde (BAAA) into the fluorescent product BODIPY-aminoacetate (BAA). Although each ALDH isoform plays an individual role in PCa biology, their mutual functional interplay also contributes to PCa progression. Thus, ALDH proteins are markers and functional regulators of CSC properties, representing an attractive target for cancer treatment. In this review, we discuss the current state of research regarding the role of individual ALDH isoforms in PCa development and progression, their possible therapeutic targeting, and provide an outlook for the future advances in this field.

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Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer

Cited by 22 publications

References 94 publications

Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer

Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer

CXCR3 Expression and Genome-Wide 3′ Splice Site Selection in the TCGA Breast Cancer Cohort

The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells

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