Clinical outcomes associated with pathogenic genomic instability mutations in prostate cancer: a retrospective analysis of US pharmacy and medical claims data

Liu, Jinan; Near, Aimee M.; Chiarappa, Joseph A.; Wada, Keiko; Tse, Jenny; Burudpakdee, Chakkarin; Behl, Ajay S.; Ranganath, Radhika; Antonarakis, Emmanuel S.

doi:10.1080/13696998.2019.1649267

Cited by 5 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dissimilarly, in the early-onset population of our study, we found that the frequency of PCa patients with germline mutations in DRGs was 58.3% (14/24), much higher than that in PCa patients with undefined ages (the patients diagnosed with prostate cancer at any ages, not restricted to the early-onset ages). Consistent with a recent report ( 18 ), we found that patients with DRGs’ germline mutations have higher Gleason scores, more advanced clinical stages, and more metastasis. More importantly, compared with another PCa cohort with undefined average ages in Ye et al.’s Chinese population ( 1 ), we found that early-onset PCa patients with DRGs’ mutations had a relatively younger ages (54 vs 60 years) and higher PSA levels at diagnosis (120 vs 100 ng/ml), but lower Gleason Scores (≥8, 64.3% vs 84%) and fewer metastasis (28.6% vs 71%).…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Germline Mutations in Patients With Early-Onset Prostate Cancer

et al. 2022

View full text Add to dashboard Cite

ObjectiveTo investigate the inherited mutations and their association with clinical features and treatment response in young-onset prostate cancer patients.MethodTargeted gene sequencing on 139 tumor susceptibility genes was conducted with a total of 24 patients diagnosed with PCa under the age of 63 years old. Meanwhile, the related clinical information of those patients is collected and analyzed.ResultsSixty-two germline mutations in 45 genes were verified in 22 patients. BRCA2 (20.8%) and GJB2 (20.8%) were found to be the most frequently mutated, followed by CHEK2, BRCA1, PALB2, CDKN2A, HOXB13, PPM1D, and RECQL (8.3% of each, 2/24). Of note, 58.3% (14/24) patients carry germline mutations in DNA repair genes (DRGs). Four families with HRR (homologous recombination repair)-related gene mutations were described and analyzed in detail. Two patients with BRCA2 mutation responded well to the combined treatment of androgen deprivation therapy (ADT) and radiotherapy/chemotherapy.ConclusionMutations in DRGs are more prevalent in early-onset PCa with advanced clinical stages, and these patients had shorter progression-free survival. ADT Combined with either radiotherapy or chemotherapy may be effective in treating PCa caused by HRR-related gene mutations.

show abstract

Section: Discussionsupporting

confidence: 92%

“…Germline BRCA2 and BRCA1 mutations present in 1.2% and 0.44% PCa ( 17 ), respectively. The frequency of BRCA2 mutation in early-onset PCa patients (<65 years old) could be as high as 2.2% ( 18 ). Based on these data, we hypothesized that germline mutations could be one of the important underlying mechanisms for PCa early onset.…”

Section: Introductionmentioning

confidence: 99%

Germline Mutations in Patients With Early-Onset Prostate Cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although numerous progress has been made to uncover the molecular mechanisms of PCa development and progression, the outcomes remain obscure and the inconsistencies among different published studies are obvious (Barbieri et al, 2017). The main reason for such phenomenon is generally thought to be the complexity and heterogeneity nature of PCa as a whole (Liu et al, 2019a; Thomas & Pachynski, 2018). Thus, it’s of vital significance to perform further research in this regard to validate and update the information acquired.…”

Section: Discussionmentioning

confidence: 99%

“…Up to now, by either analysis of a single dataset or integrated analysis of multiple datasets in GEO, several studies have dug out genes that exert important influence on the occurrence and progression of PCa, such as cadherin 1 (CDH1) (Fang et al, 2017), CDCA8 (Zhao et al, 2017), RPS21 (Fan et al, 2018), PIK3R1 (He et al, 2018), epithelial cell adhesion molecule (EPCAM) (Lu & Ding, 2019), LMNB1 (Song et al, 2019b), IGF2 (Tan, Jin & Wang, 2019), and IKZF1 (Tong, Song & Deng, 2019). However, the key genes detected by the above studies are largely different from each other and had little in common, and such discrepancy could be attributed to the fact that PCa is considered as a heterogenous disease as a whole (Liu et al, 2019a; Thomas & Pachynski, 2018). As a consequence, further studies in this regard is still required for the exploration and validation of key genes.…”

Section: Introductionmentioning

confidence: 96%

Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

Duan

Zeng

2019

PeerJ

View full text Add to dashboard Cite

Background Prostate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method. Methods Differentially expressed genes (DEGs) were filtered out from the GSE103512 dataset and subjected to the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein–protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The University of California Santa Cruz Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts. Results Totally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in “oxidation-reduction process” and “positive regulation of transcription from RNA polymerase II promoter”; KEGG pathway analysis enriched mostly in “metabolic pathways” and “protein digestion and absorption.” Kallikrein-related peptidase 3, cadherin 1 (CDH1), Kallikrein-related peptidase 2 (KLK2), forkhead box A1 (FOXA1), and epithelial cell adhesion molecule (EPCAM) were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant gene expression omnibus datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients. Conclusions This study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.

show abstract

“…Manuscript to be reviewed considered as a heterogenous disease as a whole (Liu et al 2019a;Thomas & Pachynski 2018).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods (v0.1)"

2019

View full text Add to dashboard Cite

Background:Prostate cancer (PCa) is a common urinary malignancy, whose molecular mechanism has not been fully elucidated. We aimed to screen for key genes and biological pathways related to PCa using bioinformatics method. Methods: Differentially expressed genes (DEGs) were filtered out from the GSE103512 dataset and subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interactions (PPI) network was constructed, following by the identification of hub genes. The results of former studies were compared with ours. The relative expression levels of hub genes were examined in The Cancer Genome Atlas (TCGA) and Oncomine public databases. The UCSC Xena online tools were used to study whether the expression of hub genes was correlated with the survival of PCa patients from TCGA cohorts.Results: Totally, 252 (186 upregulated and 66 downregulated) DEGs were identified. GO analysis enriched mainly in 'oxidation-reduction process' and 'positive regulation of transcription from RNA polymerase II promoter'; KEGG pathway analysis enriched mostly in 'metabolic pathways' and 'protein digestion and absorption'. KLK3, CDH1, KLK2, FOXA1, and EPCAM were identified as hub genes from the PPI network. CDH1, FOXA1, and EPCAM were validated by other relevant GEO datasets. All hub genes were validated by both TCGA and Oncomine except KLK2. Two additional top DEGs (ABCC4 and SLPI) were found to be associated with the prognosis of PCa patients.Conclusions: This study excavated the key genes and pathways in PCa, which might be biomarkers for diagnosis, prognosis, and potential therapeutic targets.

show abstract

Clinical outcomes associated with pathogenic genomic instability mutations in prostate cancer: a retrospective analysis of US pharmacy and medical claims data

Cited by 5 publications

References 42 publications

Germline Mutations in Patients With Early-Onset Prostate Cancer

Germline Mutations in Patients With Early-Onset Prostate Cancer

Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods

Peer Review #1 of "Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods (v0.1)"

Contact Info

Product

Resources

About