A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer

Zhang, Bo; Chen, Men Yun; Shen, Yu; Zhuo, Xian Bo; Gao, Ping; Zhou, Fu Sheng; Liang, Bo; Zu, Jun; Zhang, Qin; Suleman, Sufyan; Xu, Yi; Xu, Min; Xu, Jin; Liu, Chen Cheng; Giannareas, Nikolaos; Xia, Ji‐Han; Zhao, Yuan; Huang, Zhong Lian; Yang, Zhen; Cheng, Huai Dong; Li, Na; Yan, Hong; Li, Wei; Zhang, Min Jun; Yu, Ke; Li, Guoliang; Sun, Meng; Chen, Zhen Dong; Wei, Gong Hong; Shao, Zhi Min

doi:10.1158/0008-5472.can-17-1721

Cited by 19 publications

(15 citation statements)

References 55 publications

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“…To determine biological processes and molecular functions associated with miRNAs differentially expressed as a result of the MD, we performed pathway analysis and identified several potentially affected pathways related to breast cancer pathogenesis. We found several such pathways enriched in genes targeted by upregulated miRNAs, which was consistent with previous studies; for example, the “regulation of developmental process (GO:0050793)” pathway was the key candidate pathway related to breast cancer in Han Chinese women [ 52 ]. The “growth (GO:0040007)” and “regulation of cell proliferation (GO:0042127)” pathways were reported to be related to triple-negative breast cancer [ 53 ].…”

Section: Discussionsupporting

confidence: 90%

The Possible Influence of Mediterranean Diet on Extracellular Vesicle miRNA Expression in Breast Cancer Survivors

Kwon

Cho

et al. 2020

Cancers

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The Mediterranean diet (MD) has been reported to have beneficial effects on breast cancer and cardiovascular diseases. Recently, microRNAs (miRNAs) have been suggested as biomarkers for the diagnosis and disease prognosis in cancer and cardiovascular diseases. We evaluated the influence of the MD on the plasma-derived extracellular vesicle miRNA signature of overweight breast cancer survivors. Sixteen participants instructed to adhere to the MD for eight weeks were included in this study. To curate differentially expressed miRNAs after MD intervention, we employed two methods: significance analysis of microarrays and DESeq2. The selected miRNAs were analyzed using ingenuity pathway analysis. After an eight-week intervention, body mass index, waist circumference, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance were significantly improved. Expression levels of 798 miRNAs were comprehensively analyzed, and 42 extracellular vesicle miRNAs were significantly differentially regulated after the eight-week MD (36 were up and 6 were down-regulated). We also identified enriched pathways in genes regulated by differentially expressed 42 miRNAs, which include signaling associated with breast cancer, energy metabolism, glucose metabolism, and insulin. Our study indicates that extracellular vesicle miRNAs differentially expressed as a result of the MD might be involved in the mechanisms that relate to cardiometabolic risk factors in overweight breast cancer survivors.

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Section: Discussionsupporting

confidence: 90%

The Possible Influence of Mediterranean Diet on Extracellular Vesicle miRNA Expression in Breast Cancer Survivors

Kwon

Cho

et al. 2020

Cancers

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“…PAQR4 promotes cell proliferation and metastasis in both non-small-cell lung cancer [42] and gastric cancer [43]. C21orf58 exerts a momentous effect on breast cancer cell growth [14]. Nevertheless, the role of abnormal CBFA2T2, PAQR4 or C21orf58 in HCC remains undefined.…”

Section: Discussionmentioning

confidence: 99%

“…Recent advance in genome-sequencing technologies has investigated the prognostic prediction of gene signatures in HCC. A majority of studies have concentrated on single gene molecule at mRNA level [11][12][13][14][15][16][17]. However, multiple-gene-based signatures are more robust to evaluate HCC prognosis compared with the predictive power of single-biomarker.…”

Section: Introductionmentioning

confidence: 99%

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

et al. 2020

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Purpose: Our study is designed to develop and certify a promising prognostic signature for hepatocellular carcinoma (HCC). Materials and methods: We retrospectively analyzed mRNA expression profiles and clinicopathological data fetched from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. We formulated a prognostic seven-gene signature composed of differentially expressed mRNAs (DEmRNAs) between HCC and nonneoplastic tissues through univariate Cox regression analysis. The receiver operating characteristic (ROC) curve, survival analysis and multivariate Cox regression analysis as well as nomograms were utilized to assess the prognostic performance of the seven-gene signature. Results: The risk score based on a seven-gene signature categorized HCC subjects into a high-and low-risk group. There was significantly discrepant overall survival (OS) between patients in both groups and the corresponding ROC curve revealed a satisfactory predictive performance in HCC survival in both TCGA and GSE76427 cohort. Multivariate Cox regression analysis demonstrated that a seven-gene signature was an independently prognostic factor for HCC. Nomograms combining this prognostic signature with significant clinical characteristics conferred a crucial reference to predict the 1-,3-and 5 years OS. Conclusions: Our study defined a promising seven-gene signature and nomogram model to forecast the OS of HCC patients, which is instrumental in clinical decision and personalized therapy.

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“…As one of the novel UVB signature genes, CNFN may be utilized to predict UVB photobiological effects on the skin and skin carcinogenesis (39). Zhang et al (40) reported that CNFN was potentially important for breast cancer due to its differential expression in tumors compared with normal breast tissues. Excluding these reports, no research on CNFN and other diseases was identified.…”

Section: Discussionmentioning

confidence: 99%

Analysis of gene co‑expression network reveals prognostic significance of CNFN in patients with head and neck cancer

et al. 2019

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In patients with head and neck cancer (HNC), lymph node (N) metastases are associated with cancer aggressiveness and poor prognosis. Identifying meaningful gene modules and representative biomarkers relevant to the N stage helps predict prognosis and reveal mechanisms underlying tumor progression. The present study used a step-wise approach for weighted gene co-expression network analysis (WGCNA). Dataset GSE65858 was subjected to WGCNA. RNA sequencing data of HNC downloaded from the Cancer Genome Atlas (TCGA) and dataset GSE39366 were utilized to validate the results. Following data preprocessing, 4,295 genes were screened, and blue and black modules associated with the N stage of HNC were identified. A total of 16 genes [keratinocyte differentiation associated protein, suprabasin, cornifelin (CNFN), small proline rich protein 1B, desmoglein 1 (DSG1), chromosome 10 open reading frame 99, keratin 16 pseudogene 3, gap junction protein β2, dermokine, LY6/PLAUR domain containing 3, transmembrane protein 79, phospholipase A2 group IVE, transglutaminase 5, potassium two pore domain channel subfamily K member 6, involucrin, kallikrein related peptidase 8] that had a negative association with the N-stage in the blue module, and two genes (structural maintenance of chromosomes 4 and mutS homolog 6) that had a positive association in the black module, were identified to be candidate hub genes. Following further validation in TCGA and dataset GSE65858, it was identified that CNFN and DSG1 were associated with the clinical stage of HNC. Survival analysis of CNFN and DSG1 was subsequently performed. Patients with increased expression of CNFN displayed better survival probability in dataset GSE65858 and TCGA. Therefore, CNFN was selected as the hub gene for further verification in the Gene Expression Profiling Interactive Analysis database. Finally, functional enrichment and gene set enrichment analyses were performed using datasets GSE65858 and GSE39366. Three gene sets, namely ‘P53 pathway’, ‘estrogen response early’ and ‘estrogen response late’, were enriched in the two datasets. In conclusion, CNFN, identified via the WGCNA algorithm, may contribute to the prediction of lymph node metastases and prognosis, probably by regulating the pathways associated with P53, and the early and late estrogen response.

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A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer

Cited by 19 publications

References 55 publications

The Possible Influence of Mediterranean Diet on Extracellular Vesicle miRNA Expression in Breast Cancer Survivors

The Possible Influence of Mediterranean Diet on Extracellular Vesicle miRNA Expression in Breast Cancer Survivors

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

Analysis of gene co‑expression network reveals prognostic significance of CNFN in patients with head and neck cancer

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