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      Identification of a prognostic classifier based on EMT-related lncRNAs and the function of LINC01138 in tumor progression for lung adenocarcinoma

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          Abstract

          Purpose: This study aimed to develop a prognostic indicator based on epithelial-mesenchymal transition (EMT)-related long noncoding RNAs (lncRNAs) and explore the function of EMT-related lncRNAs in malignant progression in lung adenocarcinoma (LUAD).

          Materials and methods: A LUAD dataset was acquired from The Cancer Genome Atlas (TCGA) to identify prognostic EMT-related lncRNAs via differential expression analysis and univariate Cox regression analysis. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized for variable selection and model construction. The EMT-related prognostic index (ERPI) was calculated according to the model and served as a classifier to divide LUAD individuals into high-ERPI and low-ERPI groups. A nomogram incorporating ERPI and clinicopathological variables was constructed. TCGA-LUAD, GSE50081, and GSE31210 were used to test the predictive capacity of the ERPI and nomogram. The characteristics of the tumor microenvironment (TME) were evaluated via the ESTIMATE, TIMER, and ssGSEA algorithms. Gene set variation analysis (GSVA) and ssGSEA were used to annotate the functions of the high-ERPI and low-ERPI groups. CCK8, transwell assay, wound-healing assay, and clone formation assay were conducted to clarify the biological functions of prognostic EMT-related lncRNAs.

          Results: Ninety-seven differentially expressed EMT-related lncRNAs were identified, 15 of which were related to overall survival (OS). A prognostic signature was constructed based on 14 prognostic EMT-related lncRNAs to calculate the ERPI of each patient, and the predictive ability of ERPI was verified in TCGA, GSE50081, and GSE31210. The low-ERPI group survived longer and had a lower percentage of patients in advanced stage than the high-ERPI group. The nomogram had the highest predictive accuracy, followed by ERPI and stage. Patients with low ERPI had higher infiltration degree of immune cells and stronger immune responses than those with high ERPI. A series of in vitro experiments demonstrated that knockdown of LINC01138 dampened variability, proliferation, and motility of A549 and H460 cells.

          Conclusion: Our study developed a prognostic classifier with robust prognostic performance and clarified the biological functions of LINC01138 in LUAD, aiding in making individual treatments for patients with LUAD and dissecting the mechanism of oncogenesis.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

            A. Subramanian, P. Tamayo, V. K. Mootha … (2005)
            Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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              limma powers differential expression analyses for RNA-sequencing and microarray studies

              Matthew E. Ritchie, Belinda Phipson, Di Wu … (2015)
              limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Mol Biosci
                Journal ID (iso-abbrev): Front Mol Biosci
                Journal ID (publisher-id): Front. Mol. Biosci.
                Title: Frontiers in Molecular Biosciences
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-889X
                Publication date (Electronic): 17 August 2022
                Publication date Collection: 2022
                Volume: 9
                Electronic Location Identifier: 976878
                Affiliations
                [1] 1 Department of Oncology , Tongji Hospital , Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China
                [2] 2 Department of Pathophysiology , School of Basic Medicine , Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China
                [3] 3 Department of Thoracic Surgery , Tongji Hospital , Tongji Medical College , Huazhong University of Science and Technology , Wuhan, China
                Author notes

                Edited by: Rui Cao, Capital Medical University, China

                Reviewed by: Changwei Lin, Central South University, China

                Yisha Zhao, Zhejiang University, China

                [ † ]

                These authors have contributed equally to this work and share first authorship

                [ ‡ ]

                These authors have contributed equally to this work

                This article was submitted to RNA Networks and Biology, a section of the journal Frontiers in Molecular Biosciences

                Article
                Publisher ID: 976878
                DOI: 10.3389/fmolb.2022.976878
                PMC ID: 9428519
                PubMed ID: 36060239
                SO-VID: c5d7082a-0b35-4676-b4bd-49e391ee1378
                Copyright © Copyright © 2022 Xiao, Huang, Li, Wang, Ma, Fan, Tang, Yuan and Liu.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 23 June 2022
                Date accepted : 12 July 2022
                Categories
                Subject: Molecular Biosciences
                Subject: Original Research

                Keywords: epithelial-mesenchymal transition,lncrna,lung adenocarcinoma,prognosis,tumor microenvironment
                Data availability:
                Keywords: epithelial-mesenchymal transition, lncrna, lung adenocarcinoma, prognosis, tumor microenvironment

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