Expression of <i>miR-18a</i> and <i>miR-210</i> in Normal Breast Tissue as Candidate Biomarkers of Breast Cancer Risk

Shidfar, Ali; Scholtens, Denise M.; Bischof, Jared M.; Sullivan, Megan; Ivancic, David; Vanin, Elio F.; Soares, Marcelo B.; Wang, Jun; Khan, Seema A.

doi:10.1158/1940-6207.capr-16-0177

Cited by 29 publications

(21 citation statements)

References 40 publications

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“…420 Although we do not have any data to explain why our results are different from their observation, one possibility may be a result of different biology of breast cancers that originate from different ethnic backgrounds 21 .…”

Section: Discussioncontrasting

confidence: 88%

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

et al. 2017

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Background MicroRNAs (miRNAs) play a critical role in the carcinogenesis and progression of breast cancer. MiRNA-205 has tumor suppressive properties, whereas miRNA-18a has both oncogenic and tumor suppressive roles. MiRNA-744’s role in breast cancer is unknown, but is tumor-suppressive in vitro. We hypothesize that high expression of all three miRNAs is associated with a better survival based on their known functions in breast cancer. Methods All data was obtained from the Cancer Genome Atlas (TCGA). Expression of miRNA-18a, miRNA-205, and miRNA-744 were retrieved from the Genomic Data Commons (GDC) data portal for analyses. After miRNA-specific thresholds were derived and used to group the patients into a high or low expression group, survival data was calculated using the Cox proportional hazard model. Further subanalyses separating the patients based on receptor status and AJCC 7th edition TNM staging were similarly compared. Results 1052/1097 samples logged in TCGA had clinical data and miRNA-sequence datasets on the miRNAs of interest. High expression of miRNA-18a (p=0.079), miRNA-205 (p=0.034) and miRNA-744 (p=0.0135) was associated with a better survival. On subanalysis, estrogen receptor (ER), progesterone receptor (PR) positive, and lymph node negative disease had a statistically significant survival advantage with miRNA-18a, miRNA-205 and miRNA-744 high expression. Conclusions By utilizing a big dataset (TCGA) with sufficient statistical power, we found that high expression of miRNA-18a, miRNA-205, and miRNA-744 in the breast tumor samples were all associated with better overall survival in ER/PR positive, lymph node negative disease supporting their role as a tumor suppressor in breast cancer.

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Section: Discussioncontrasting

confidence: 88%

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

et al. 2017

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“…Recently, the application of miRNAs as biomarkers for cancer diagnosis and prognosis has gained much attention in recent years [ 39 ]. Accumulating evidence supports that their abnormal expression levels associated with various tumors, such as lung cancer, breast cancer, and cervical cancer [ 40 , 41 ]. More importantly, miRNAs are extremely stable and present in various biological materials, like serum, plasma, and tissue.…”

Section: Discussionmentioning

confidence: 99%

MiR-205 as a promising biomarker in the diagnosis and prognosis of lung cancer

Liu

Sun

et al. 2017

Oncotarget

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MicroRNA-205 (miR-205) was revealed as a novel diagnostic and prognostic biomarker for lung cancer, but the results in the published papers were inconsistent. This meta-analysis aimed to investigate the diagnostic and prognostic roles of miR-205 in patients with lung cancer. Totally, 16 eligible articles were included, among which 10 articles investigated the diagnostic value of miR-205, 5 articles examined its prognostic values, and 1 article studied both diagnostic and prognostic values. For the diagnostic meta-analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the overall area under the curve of miR-205 for patients with lung cancer were 0.88 (95% CI = 0.78 – 0.94), 0.78 (95% CI = 0.66 – 0.86), 4.00 (95% CI = 2.47 – 6.49), 0.16 (95% CI = 0.08 – 0.30), 25.86 (95% CI = 9.29 – 71.95), and 0.90 (95% CI = 0.87 – 0.92), respectively, indicating that miR-205 is a useful biomarker for diagnostic of lung cancer. The subgroup analysis further demonstrated that miR-205 had an excellent overall accuracy for detection with tissue samples compare with blood samples. For the prognostic meta-analysis, the pooled outcome of the disease-free survival and recurrence-free survival analyses revealed that increased miR-205 levels had a protective role in the prognosis of patients with lung cancer (pooled HR = 0.86, 95% CI: 0.78-0.96, z = 2.83, P = 0.005). In conclusion, miR-205 may be a promising biomarker for detection, predicting the recurrence of patients with lung cancer.

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“…Nevertheless, many of it features can be tested. 73 . We have retrieved the BBB paraffin blocks of subjects who subsequently developed breast cancer (cases) and from age matched controls, who have not developed breast cancer to date.…”

Section: Hypothesismentioning

confidence: 99%

Somatic Genetic Aberrations in Benign Breast Disease and the Risk of Subsequent Breast Cancer

Zeng¹,

et al. 2019

Preprint

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One Sentence Summary: Genetic aberrations in benign breast lesions distinguish breast cancer cases from controls and predict cancer risk.Abstract: It is largely unknown how the risk of development of breast cancer is transduced by somatic genetic alterations. To address this lacuna of knowledge and acknowledging that benign breast disease (BBD) is an established risk factor for breast cancer, we established a case-control study: The Benign Breast & Cancer Risk (BBCAR) Study. Cases are women with BBD who developed subsequent invasive breast cancer (IBC) at least 3 years after the biopsy and controls are women with BBD who did not develop IBC (median follow-up 16.6 years). We selected 135 cases and individually matched controls (1:2) to cases based on age and type of benign disease: non-proliferative or proliferation without atypia. Whole exome sequencing was performed on DNA from the benign lesions and from subsets with available germline DNA or tumor DNA. Although the number of cases and controls with copy number variation data is limited, several amplifications and deletions are exclusive to the cases. In addition to two known mutational signatures, a novel signature was identified that is significantly (p=0.007) associated with triple negative breast cancer. The somatic mutation rate in benign lesions is similar to that of invasive breast cancer and does not differ between cases and controls. Two mutated genes are significantly associated with time to the diagnosis of breast cancer, and mutations shared between the benign biopsy tissue and the breast malignancy for the ten cases for which we had matched pairs were identified. BBD tissue is a rich source of clues to breast oncogenesis.

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Expression of miR-18a and miR-210 in Normal Breast Tissue as Candidate Biomarkers of Breast Cancer Risk

Cited by 29 publications

References 40 publications

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

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

MiR-205 as a promising biomarker in the diagnosis and prognosis of lung cancer

Somatic Genetic Aberrations in Benign Breast Disease and the Risk of Subsequent Breast Cancer

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