Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome: validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an independent cohort

Pinto, Ricardo; Assis, Joana; Nogueira, Augusto; Pereira, Carina; Coelho, Sara; Brandão, Mariana; Dias, João; Alves, Sara; Pereira, Deolinda; Medeiros, Rui

doi:10.1038/s41397-018-0056-y

Cited by 12 publications

(4 citation statements)

References 40 publications

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“…TREM2, a novel pattern recognition receptor family member, is generally regarded to be an enhancer of immune responses (33). According to pharmacogenomics, NRG3 rs1649942 genetic variants have been validated to affect epithelial ovarian cancer first-line treatment outcomes, which confirmed patients carrying the NRG3 rs1649942 A allele presented a significantly longer OS time (34). In addition, CLC and TNFAIP6, which are cytokine receptors, are involved in disease progression and the immune response (35) in a variety of tumors, such as gastric cancer (36), breast cancer (37) and urothelial carcinomas (38).…”

Section: Discussionmentioning

confidence: 99%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

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Cytokines play an important role in the development of tumors. The purpose of the present study was to evaluate the mechanisms and cytokine level changes after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). The Short Time-series Expression Miner (STEM) program was utilized to cluster cytokine expression profiles from the day before TACE to day 21 post-TACE. Based on the identified significant signatures, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Cytokines were serially monitored in 60 evaluable patients to identify the results of the STEM program. Examination of the significant signatures identified 6 significant time-varied expression patterns for 507 cytokines (profiles 16, 18, 28, 41, 42 and 43). GO analysis was enriched in 'cytokine receptor-binding' and 'cytokine receptor activity', and the identified signaling pathways included 'cytokine-cytokine receptor interaction' and the 'JAK-STAT signaling pathway'. Ciliary neurotrophic factor (CNTF) level was increased early after TACE, reaching a peak on day 7 before finally decreasing from day 14 onwards, and was significantly positively correlated with aminotransferase level. Serum levels of pre-TACE IL-10 predicted the local tumor response and overall survival (OS) of the patients, while serum levels of post-TACE IL-1β only indicated the local tumor response of the patient. Overall, the present study identified cytokine time-series expression profiles of patients with HCC undergoing TACE. Early phase increases in CNTF after TACE were associated with post-treatment hepatic injury. IL-1β may reflect an objective response after TACE, while IL-10 may represent a biomarker for OS and the objective response pre-TACE, which may help patients with HCC to benefit from TACE.

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Section: Discussionmentioning

confidence: 99%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

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“…Of interest, some candidates related to sperm and infertility were identified, containing MORC1 [46], TDRD9 [47], ZFYVE21 [48], ADGRB3 [49], SPAG17 [50,51], CKB [52], and WDR3 [53], which may have effects on sperm motility and fertilization. Additionally, we identified some candidate genes linked to reproductive diseases, such as NRG3 [54] and XRCC3 [55] for ovarian cancer, and BAG5 [56], CKB [57] and XRCC3 [55] for endometriosis. Taken together, these data indicate the importance of reproductive health in lambing.…”

Section: Candidate Genes Likely Functioning In Prolificacymentioning

confidence: 99%

Litter Size of Sheep (Ovis aries): Inbreeding Depression and Homozygous Regions

Lin

Wang

et al. 2021

Genes

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Ovine litter size (LS) is an important trait showing variability within breeds. It remains largely unknown whether inbreeding depression on LS exists based on genomic homozygous regions, and whether the homozygous regions resulted from inbreeding are significantly associated with LS in sheep. We here reanalyze a set of single nucleotide polymorphism (SNP) chip of six breeds to characterize the patterns of runs of homozygosity (ROH), to evaluate inbreeding levels and inbreeding depressions on LS, and to identify candidate homozygous regions responsible for LS. Consequently, unique ROH patterns were observed among six sheep populations. Inbreeding depression on LS was only found in Hu sheep, where a significant reduction of 0.016, 0.02, and 0.02 per 1% elevated inbreeding FROH4–8, FROH>8 and the total inbreeding measure was observed, respectively. Nine significantly homozygous regions were found for LS in Hu sheep, where some promising genes for LS possibly via regulation of the development of oocytes (NGF, AKT1, and SYCP1), fertilization (SPAG17, MORC1, TDRD9, ZFYVE21, ADGRB3, and CKB), embryo implantation (PPP1R13B, INF2, and VANGL1) and development (DPPA2, DPPA4, CDCA4, CSDE1, and ADSSL1), and reproductive health (NRG3, BAG5, CKB, and XRCC3) were identified. These results from the present study would provide insights into the genetic management and complementary understandings of LS in sheep.

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“…An intronic variant of NRG1 was also found to be associated with non-small cell lung cancer survival [ 11 ]. Moreover, a polymorphism in NRG3 might lead to better overall survival in patients with stage IV epithelial ovarian cancer who are receiving first-line treatment [ 12 ]. However, the roles of genetic variants within the NRG signalling pathway in prostate cancer are unclear, and investigations into their functions may provide insight into the etiology and prognostic significance of the disease.…”

Section: Introductionmentioning

confidence: 99%

NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

Huang

Chen

et al. 2021

Biomedicines

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Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

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Pharmacogenomics in epithelial ovarian cancer first-line treatment outcome: validation of GWAS-associated NRG3 rs1649942 and BRE rs7572644 variants in an independent cohort

Cited by 12 publications

References 40 publications

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

Litter Size of Sheep (Ovis aries): Inbreeding Depression and Homozygous Regions

NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

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