Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the Cancer Genome Atlas (TCGA)

Kim, Sara Y.; Kawaguchi, Tsutomu; Yan, Li; Young, Joseph C.; Qi, Qianya; Takabe, Kazuaki

doi:10.1245/s10434-017-5984-2

Cited by 52 publications

(47 citation statements)

References 25 publications

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“…RNA seq v2 z-scores and clinical data were obtained through the cBioportal for Cancer Genomics (http:// cbioportal.org) on January 15th, 2018, and processed as previously described. 40,41 Of 440 cases, there were 369 primary tumors available for gene expression data from RNA sequence. Two recurrent tumor samples from two patients whose primary tumors were also registered were excluded from our study to avoid duplication of patients.…”

Section: Data Acquisition and Preprocessingmentioning

confidence: 99%

Low DMT1 Expression Associates With Increased Oxidative Phosphorylation and Early Recurrence in Hepatocellular Carcinoma

Hoki

Katsuta

Yan

et al. 2019

Journal of Surgical Research

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Background: Despite a high rate of recurrences, long-term survival can be achieved after the resection of hepatocellular carcinoma (HCC) with effective local treatment. Discovery of adverse prognostic variables to identify patients with high risk of recurrence could improve the management of HCC. Accumulating evidence showing a link between carcinogenesis and increased expression of iron import proteins and intracellular iron prompted us to investigate a role of divalent metal-ion transporter-1 (DMT1) that binds and regulates a variety of divalent metals in HCC. Materials and methods: Clinical and gene expression data from RNA seq in 369 HCC patients were obtained from The Cancer Genome Atlas. Disease-free survival was compared between DMT1 high-and low-expressing tumors, and gene set enrichment analysis was conducted. Results: Patients with lower expression of DMT1 exhibited significantly worse disease-free survival compared with the DMT1 high group (P ¼ 0.044), notably in advanced-stage patients (P ¼ 0.008). DMT1 expression did not differ in etiologies, stages, and differentiation status of HCC. Interestingly, DMT1 expression levels inversely associated with cellular respiratory function in HCC. Furthermore, gene set enrichment analysis revealed that metabolism-related gene sets such as glycolysis, oxidative phosphorylation, and reactive oxygen species pathway were significantly enriched in the DMT1 low-expressing HCC.

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Section: Data Acquisition and Preprocessingmentioning

confidence: 99%

Low DMT1 Expression Associates With Increased Oxidative Phosphorylation and Early Recurrence in Hepatocellular Carcinoma

Hoki

Katsuta

Yan

et al. 2019

Journal of Surgical Research

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“…The most well-known example is that overexpression of miR-21 and miR-210 results in shorter overall survival of BC patients [7]. The Cancer Genome Atlas (TCGA) provided us with complicated clinical characteristics and more than cancer genomics [8]. Screened by 1000 BC samples, we retrieved to make an understanding of the relationship of miRNA expression level with the prognosis and outcome of BC patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Tang

Zeng³

et al. 2019

Disease Markers

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To identify the novel, noninvasive biomarkers to assess the outcome and prognosis of breast cancer (BC), patients with high sensitivity and specificity are greatly desired. Herein, the miRNA expression profile and matched clinical features of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. The preliminary candidates were screened out by the univariate Cox regression test. Then, with the help of LASSO Cox regression analysis, the hsa-let-7b, hsa-mir-101-2, hsa-mir-135a-2, hsa-mir-22, hsa-mir-30a, hsa-mir-31, hsa-mir-3130-1, hsa-mir-320b-1, hsa-mir-3678, hsa-mir-4662a, hsa-mir-4772, hsa-mir-493, hsa-mir-556, hsa-mir-652, hsa-mir-6733, hsa-mir-874, and hsa-mir-9-3 were selected to construct the overall survival (OS) predicting signature, while the hsa-mir-130a, hsa-mir-204, hsa-mir-217, hsa-mir-223, hsa-mir-24-2, hsa-mir-29b-1, hsa-mir-363, hsa-mir-5001, hsa-mir-514a-1, hsa-mir-624, hsa-mir-639, hsa-mir-659, and hsa-mir-6892 were adopted to establish the recurrence-free survival (RFS) predicting signature. Referring to the median risk scores generated by the OS and RFS formulas, respectively, subgroup patients with high risk were strongly related to a poor OS and RFS revealed by Kaplan-Meier (K-M) plots. Meanwhile, receiver operating curve (ROC) analysis validated the accuracy and stability of these two signatures. When stratified by clinical features, such as tumor stage, age, and molecular subtypes, we found that the miRNA-based OS and RFS classifiers were still significant in predicting OS/RFS and showed the best predictive values than any other features. Besides, functional prediction analyses showed that these targeted genes of the enrolled miRNAs were enriched in cancer-associated pathways, such as MAPK/RTK, Ras, and PI3K-Akt signaling pathways. In summary, our observations demonstrate that the novel miRNA-based OS and RFS signatures are independent prognostic indicators for BC patients and worthy to be validated by further prospective studies.

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“…In recent years, detailed information regarding prognosis evaluation for cancer patients can be effectively provided by genome‐wide expression profiling detection . Numerous studies have evaluated the prognostic roles of array‐based gene expression signatures acquired from tumours .…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have evaluated the prognostic roles of array‐based gene expression signatures acquired from tumours . Several gene signatures have also been established to distinguish the prognosis of patients beyond the BC clinicopathologic features; however, most of them are not used clinically . Thus, identifying a novel and practical gene signature to predict patients’ prognosis is urgently needed and of great clinical significance.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, detailed information regarding prognosis evaluation for cancer patients can be effectively provided by genome-wide expression profiling detection. [14][15][16][17] Numerous studies have evaluated the prognostic roles of array-based gene expression signatures acquired from tumours. 14,18,19 Several gene signatures have also been established to distinguish the prognosis of patients beyond the BC clinicopathologic features; however, most of them are not used clinically.…”

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confidence: 99%

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Identification of a 4‐mRNA metastasis‐related prognostic signature for patients with breast cancer

Xie

Wang

Shi

et al. 2018

J Cellular Molecular Medi

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Metastasis‐related mRNAs have showed great promise as prognostic biomarkers in various types of cancers. Therefore, we attempted to develop a metastasis‐associated gene signature to enhance prognostic prediction of breast cancer (BC) based on gene expression profiling. We firstly screened and identified 56 differentially expressed mRNAs by analysing BC tumour tissues with and without metastasis in the discovery cohort (GSE102484, n = 683). We then found 26 of these differentially expressed genes were associated with metastasis‐free survival (MFS) in the training set (GSE20685, n = 319). A metastasis‐associated gene signature built using a LASSO Cox regression model, which consisted of four mRNAs, can classify patients into high‐ and low‐risk groups in the training cohort. Patients with high‐risk scores in the training cohort had shorter MFS (hazard ratio [HR] 3.89, 95% CI 2.53‐5.98; P < 0.001), disease‐free survival (DFS) (HR 4.69, 2.93‐7.50; P < 0.001) and overall survival (HR 4.06, 2.56‐6.45; P < 0.001) than patients with low‐risk scores. The prognostic accuracy of mRNAs signature was validated in the two independent validation cohorts (GSE21653, n = 248; GSE31448, n = 246). We then developed a nomogram based on the mRNAs signature and clinical‐related risk factors (T stage and N stage) that predicted an individual's risk of disease, which can be assessed by calibration curves. Our study demonstrated that this 4‐mRNA signature might be a reliable and useful prognostic tool for DFS evaluation and will facilitate tailored therapy for BC patients at different risk of disease.

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Clinical Relevance of microRNA Expressions in Breast Cancer Validated Using the Cancer Genome Atlas (TCGA)

Cited by 52 publications

References 25 publications

Low DMT1 Expression Associates With Increased Oxidative Phosphorylation and Early Recurrence in Hepatocellular Carcinoma

Low DMT1 Expression Associates With Increased Oxidative Phosphorylation and Early Recurrence in Hepatocellular Carcinoma

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Identification of a 4‐mRNA metastasis‐related prognostic signature for patients with breast cancer

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