Multianalyte quantitative competitive PCR on optically encoded microspheres for an eight-gene panel related to prostate cancer

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

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A research-based gene panel to investigate breast, ovarian and prostate cancer genetic risk

PLoS ONE ◽

10.1371/journal.pone.0220929 ◽

2019 ◽

Vol 14 (8) ◽

pp. e0220929 ◽

Cited By ~ 1

Author(s):

Madison R. Bishop ◽

Anna L. W. Huskey ◽

John Hetzel ◽

Nancy D. Merner

Keyword(s):

Prostate Cancer ◽

Genetic Risk ◽

Gene Panel ◽

Cancer Genetic

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Prevalence of mutations in a comprehensive DNA damage repair gene panel in Chinese prostate cancer patients

European Urology Open Science ◽

10.1016/s2666-1683(20)33642-9 ◽

2020 ◽

Vol 19 ◽

pp. e1568

Author(s):

Y. Wei ◽

J. Wu ◽

Y. Zhu ◽

D. Ye

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Cancer Patients ◽

Dna Damage Repair ◽

Gene Panel ◽

Repair Gene ◽

Damage Repair

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Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up

BMC Medicine ◽

10.1186/s12916-020-01834-0 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Heather Johnson ◽

Jinan Guo ◽

Xuhui Zhang ◽

Heqiu Zhang ◽

Athanasios Simoulis ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cancer Diagnosis ◽

Multivariate Logistic Regression Analysis ◽

Gene Panel ◽

Urine Test ◽

Non Invasive ◽

Clinically Significant ◽

Benign Prostate

Abstract Background Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. Conclusions The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

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A six-gene panel that predicts survival in men with castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.4539 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 4539-4539

Author(s):

S. K. Subudhi ◽

G. Heller ◽

A. Anand ◽

D. C. Danila ◽

M. Fleisher ◽

...

Keyword(s):

Prostate Cancer ◽

Gene Panel ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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DNA repair gene panel mutations in young onset prostate cancer cases in the.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.18 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 18-18

Author(s):

Ros A. Eeles ◽

Daniel Leongamornlert ◽

Ed Saunders ◽

Sarah Wakerell ◽

Ian Whitmore ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Gene Panel ◽

Western World ◽

Tumour Suppressor Genes ◽

Illumina Hiseq ◽

Clinical Prognosis ◽

Young Onset ◽

Adaptive Combination ◽

Dna Repair Gene

18 Background: Prostate cancer (PrCa) is the most common solid tumour in men in the Western world. There is substantial evidence that PrCa predisposition is due both to common and rare germline variation. Methods: We screened 167 genes from DNA damage response and repair pathways, within a UK based cohort of young onset cases (diagnosed at < 65 years) and controls. Samples were sequenced using a custom Agilent SureSelectXT bait library and Illumina HiSeq technology and processed using a BWA/GATK 2.8 pipeline. Following sample QC, data were analysed from 1,285 PrCa cases and 1,163 controls. Results: We identified 5,086 single nucleotide variants (SNVs) and 175 indels; 233 unique protein truncating variants (PTVs) with MAF < 0.5% in controls were found in 97 genes of the screening panel. The total proportion of PTV carriers in cases was higher than in controls (14.5% vs. 11.6%, P = 0.036; OR = 1.29, 95% CI 1.01-1.64). This enrichment was greater within the previously reported BROCA gene set of 22 tumour suppressor genes (4.5% vs 2.2%, P = 2.5x10-3; OR = 2.07, 95% CI 1.28-3.34). To identify genes which best to distinguish PrCa cases from controls, we applied the adaptive combination of P values algorithm, ADA, for genes with at least 2 carriers of PTVs. This analysis selected 10 genes, (OR = 3.37, 95% CI 2.05-5.66, PADA= 5.99x10-3); men with PTVs in these were about 3.4-fold more likely to have PrCa (5.8% vs. 1.8%). We subsequently compared aggressive cases (Gleason score ≥ 8, n = 204) with non-aggressive cases (Gleason score ≤ 7, n = 1049) and lethal PrCa cases (cause of death PrCa, n = 183) with indolent cases (Gleason score ≤ 6, n = 563) to evaluate genes associated with poor clinical prognosis. Using ADA, 4 genes were selected for aggressive PrCa ( PADA= 0.006) and 2 of these also for lethal PrCa ( PADA= 0.057). Conclusions: These gene sets provide an 11 gene panel which could be used for clinical testing and will help to facilitate the development of a PrCa specific sequencing panel with both predictive and prognostic potential.

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Germline mutation in multiple primary malignancies associated with prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17505 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17505-e17505

Author(s):

Yiming Gong ◽

Liancheng Fan ◽

Yinjie Zhu ◽

Jiahua Pan ◽

Jianjun Sha ◽

...

Keyword(s):

Prostate Cancer ◽

Germline Mutation ◽

Hereditary Disease ◽

Gene Panel ◽

Blood Samples ◽

Multiple Primary Malignancies ◽

Esr1 Gene ◽

Pathway Gene ◽

Multiple Primary ◽

Germline Variation

e17505 Background: Multiple primary malignancies (MPM) are described as that one individual develop several malignancies that originate from different tissues at the same time or separated (different histology in different location). MPM are also considered as an indicator of germline mutation or hereditary disease. Here we performed next generation sequencing-based 642-gene panel test on the MPM patients to figure out the candidate germline mutation essential for multiple tumorigenesis. Methods: Blood samples from 27 patients diagnosed as MPM with prostate cancer and at least one additional primary cancer from 2018.12 to 2019.12 were collected to detect the germline variation of 642 gene panel. Meanwhile 25 blood samples from patients only diagnosed as prostate cancer were taken as control. After the sequencing results were obtained, the differences between the multiple primary and single primary cohorts were counted. Results: Statistical analysis of the mutations in the multi-primary and single-primary cohorts revealed that differences were concentrated in the following six genes: ESR1, PTPRB, CIC, ANKRD11, BRCA2, MLH1. It was found that the mutations of p.G145S and p.P146Q (frequency 18.5%) of ESR1 gene and p.G1150W (frequency 14.8%) of PTPRB gene which related to angiogenesis were only found in multiple primary cohort. And mutations of growth factor pathway gene CIC (frequency 22.2%), mutation of chromatin remodeling family gene ANKRD11, and two genes of DDR pathway (BRCA2, MLH1) appeared higher in multiple primary cohort, although there was no statistical difference. Conclusions: We found for the first time that the p.G145S and p.P146Q mutations of the estrogen receptor ESR1 gene and the p.G1150W mutation of the angiogenesis-related PTPRB gene may be the drivers of multiple primary prostate cancer, which need further study.

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