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      Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

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          Abstract

          Background

          Triple-negative breast cancer (TNBC) remains the most incurable subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. It is generally acknowledged that epithelial-mesenchymal transition (EMT) is the key step in tumor metastasis.

          Methods

          With the application of TCGA and GEO databases, we identified EMT-related lncRNAs by the Cox univariate regression analysis. Optimum risk scores were calculated and used to divide TNBC patients into high-/low-risk subgroups by the median value using the Lasso regression analysis. The Kaplan–Meier and ROC curve analyses were applied for model validation. Then, we assessed the risk model from multi-omic aspects including immune infiltration, drug sensitivity, mutability spectrum, signaling pathways, and clinical indicators. We also analyzed the expression pattern of lncRNAs involved in the model using qRT-PCR in TNBC cell lines and constructed the ceRNA network.

          Results

          The risk model was composed of EMT-related long noncoding RNAs (lncRNAs), which seemed to be valuable in the prognostic prediction of TNBC patients. The model could act as an independent prognostic factor of TNBC and showed a robust prognostic ability in the stratification analysis. Further investigation demonstrated that the expression of lncRNAs was different between high aggressive and low aggressive TNBC cell lines, as well as TNBC patients.

          Conclusions

          Together, our study successfully established a risk model with great accuracy and efficacy in the prognostic prediction of TNBC patients.

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          Most cited references74

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          Functional Classification and Experimental Dissection of Long Noncoding RNAs

          Over the last decade, it has been increasingly demonstrated that the genomes of many species are pervasively transcribed, resulting in the production of numerous long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many types of DNA regulatory elements, such as enhancers and promoters, regularly initiate bidirectional transcription. Thus, discerning functional noncoding transcripts from a vast transcriptome is a paramount priority, and challenge, for the lncRNA field. In this review, we aim to provide a conceptual and experimental framework for classifying and elucidating lncRNA function. We categorize lncRNA loci into those that regulate gene expression in cis versus those that perform functions in trans , and propose an experimental approach to dissect lncRNA activity based on these classifications. These strategies to further understand lncRNAs promise to reveal new and unanticipated biology, with great potential to advance our understanding of normal physiology and disease.
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            EMT: 2016.

            The significant parallels between cell plasticity during embryonic development and carcinoma progression have helped us understand the importance of the epithelial-mesenchymal transition (EMT) in human disease. Our expanding knowledge of EMT has led to a clarification of the EMT program as a set of multiple and dynamic transitional states between the epithelial and mesenchymal phenotypes, as opposed to a process involving a single binary decision. EMT and its intermediate states have recently been identified as crucial drivers of organ fibrosis and tumor progression, although there is some need for caution when interpreting its contribution to metastatic colonization. Here, we discuss the current state-of-the-art and latest findings regarding the concept of cellular plasticity and heterogeneity in EMT. We raise some of the questions pending and identify the challenges faced in this fast-moving field.
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              Triple-negative breast cancer.

              Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                jo
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2021
                27 November 2021
                : 2021
                : 9219961
                Affiliations
                1Department of Medical Oncology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
                2Department of Medical Oncology, The Huaian Clinical College of Xuzhou Medical University, Huai'an, Jiangsu, China
                3Department of Breast and Thyroid Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
                Author notes

                Academic Editor: Jimei Wang

                Author information
                https://orcid.org/0000-0002-9899-0924
                https://orcid.org/0000-0001-9976-5086
                https://orcid.org/0000-0001-7200-6186
                Article
                10.1155/2021/9219961
                8643262
                34873403
                f392c4c0-89d3-46bf-9b00-6c11e13289c3
                Copyright © 2021 Jiani Guo et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 October 2021
                : 8 November 2021
                Funding
                Funded by: Six Talent Peaks Project in Jiangsu Province
                Award ID: LGY2017051
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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