Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer

Dai, Weiyu; Xiao, Yizhi; Tang, Weimei; Hong, Linjie; Zhang, Jieming; Pei, Miaomiao; Lin, Jing; Liu, Side; Wu, Xiaosheng; Li, Xiang; Wang, Jide

doi:10.3389/fgene.2021.661306

Cited by 21 publications

(18 citation statements)

References 62 publications

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“…The EMT process could speed up the invasion, dissemination, and migration rates of cancer cells, which contributes to the rapid deterioration of disease and chemotherapeutic resistance. EMT markers were proven to be a critical prognosticator for different tumors, including glioma, endometrial cancer, and also GC (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Four-Gene-Based SERM Signature for Prognostic and Drug Sensitivity Prediction in Gastric Cancer

Jia

Chen

et al. 2022

Front. Oncol.

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BackgroundGastric cancer (GC) is a highly molecular heterogeneous tumor with poor prognosis. Epithelial-mesenchymal transition (EMT) process and cancer stem cells (CSCs) are reported to share common signaling pathways and cause poor prognosis in GC. Considering about the close relationship between these two processes, we aimed to establish a gene signature based on both processes to achieve better prognostic prediction in GC.MethodsThe gene signature was constructed by univariate Cox and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses by using The Cancer Genome Atlas (TCGA) GC cohort. We performed enrichment analyses to explore the potential mechanisms of the gene signature. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves were implemented to assess its prognostic value in TCGA cohort. The prognostic value of gene signature on overall survival (OS), disease-free survival (DFS), and drug sensitivity was validated in different cohorts. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation of the prognostic value of gene signature for OS and DFS prediction was performed in the Fudan cohort.ResultsA prognostic signature including SERPINE1, EDIL3, RGS4, and MATN3 (SERM signature) was constructed to predict OS, DFS, and drug sensitivity in GC. Enrichment analyses illustrated that the gene signature has tight connection with the CSC and EMT processes in GC. Patients were divided into two groups based on the risk score obtained from the formula. The Kaplan-Meier analyses indicated high-risk group yielded significantly poor prognosis compared with low-risk group. Pearson’s correlation analysis indicated that the risk score was positively correlated with carboplatin and 5-fluorouracil IC50 of GC cell lines. Multivariate Cox regression analyses showed that the gene signature was an independent prognostic factor for predicting GC patients’ OS, DFS, and susceptibility to adjuvant chemotherapy.ConclusionsOur SERM prognostic signature is of great value for OS, DFS, and drug sensitivity prediction in GC, which may give guidance to the development of targeted therapy for CSC- and EMT-related gene in the future.

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Section: Introductionmentioning

confidence: 99%

Identification of a Four-Gene-Based SERM Signature for Prognostic and Drug Sensitivity Prediction in Gastric Cancer

Jia

Chen

et al. 2022

Front. Oncol.

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“…Finally, seven studies were found ( Kiyozumi et al, 2018 ; Li S. S et al, 2020 ; Luo et al, 2020 ; Wang et al, 2020 ; Dai et al, 2021 ; Li et al, 2021 ; Song et al, 2021 ). Dai et al constructed a prognostic model for five genes including PLOD2 , which was subsequently validated by RT-PCR in normal tissue and gastric cancer cell lines ( Dai et al, 2021 ). However, their study did not perform analyses related to tumor immunity (including infiltrating immune cells, TMB, etc.).…”

Section: Discussionmentioning

confidence: 99%

“…In order to investigate the research status of PLOD2 and gastric cancer, we conducted a search on the PubMed using the following search strategy: [“stomach neoplasms” (Title/Abstract) OR “stomach neoplasms” (MeSH Terms) OR “gastric adenocarcinoma” (Title/Abstract)] AND [“PLOD2” (Title/Abstract)]. Finally, seven studies were found ( Kiyozumi et al, 2018 ; Li S. S et al, 2020 ; Luo et al, 2020 ; Wang et al, 2020 ; Dai et al, 2021 ; Li et al, 2021 ; Song et al, 2021 ). Dai et al constructed a prognostic model for five genes including PLOD2 , which was subsequently validated by RT-PCR in normal tissue and gastric cancer cell lines ( Dai et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of PLOD2

Kong

Zhao

et al. 2022

Front. Genet.

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Some previous studies have shown that PLOD2 has some value in tumorigenesis. However, the broad significance of PLOD2 has not been discussed in depth. This study was aimed at elaborated and summarized the value of PLOD2 in various tumors. First, we integrated GTEx, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases to analyze the expression of PLOD2, and found that it was expressed differently in normal tissues and significantly highly expressed in most tumors compared with normal tissues. Second, our analysis revealed that PLOD2 expression was negatively correlated with the prognosis of several tumors. For gastric cancer, the median overall survival time was significantly higher in the PLOD2 low expression group [HR 0.616 (95%CI 0.442–0.858), p = 0.004]. Third, for tumor immunity, PLOD2 was significantly associated with tumor infiltration, including immune infiltrating cells; immune checkpoint expression; immune microenvironment scores (immune score, stromal score and estimate scores); immunotherapy-related scores (tumor mutational burden, microsatellite instability, tumor neoantigen burden); expression of DNA repair genes Mismatch Repairs and methyltransferase; and enrichment analyses identified PLOD2-associated terms and pathways. Lastly, twenty pairs of gastric cancer and adjacent immunohistochemistry showed that PLOD2 was significantly overexpressed in gastric cancer (p < 0.001). Collectively, PLOD2 played a significant role in tumorigenesis and maybe serve as a potential biomarker for diagnosis and prognosis in cancers.

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“…To confirm that stiffness has a physiological function in cells of the same genetic origin during a cell state transition, QPR is applied to a cellular model of EMT (see also below) (Zhang et al, 2014). The hypothesis is supported by a novel EMT-based gene signature, encompassing ITGAV, DAB2, SERPINE1, MATN3, and PLOD2, that has been identified recently for gastric cancer (Dai et al, 2021). In line with expectations, the QPR measurements of stiffness and viscosity are related to EMT status (Nguyen et al, 2020).…”

Section: Novel Contact Free Measurement Technique Of Viscoelasticitymentioning

confidence: 96%

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Mierke

2022

Front. Cell Dev. Biol.

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Viscoelasticity and its alteration in time and space has turned out to act as a key element in fundamental biological processes in living systems, such as morphogenesis and motility. Based on experimental and theoretical findings it can be proposed that viscoelasticity of cells, spheroids and tissues seems to be a collective characteristic that demands macromolecular, intracellular component and intercellular interactions. A major challenge is to couple the alterations in the macroscopic structural or material characteristics of cells, spheroids and tissues, such as cell and tissue phase transitions, to the microscopic interferences of their elements. Therefore, the biophysical technologies need to be improved, advanced and connected to classical biological assays. In this review, the viscoelastic nature of cytoskeletal, extracellular and cellular networks is presented and discussed. Viscoelasticity is conceptualized as a major contributor to cell migration and invasion and it is discussed whether it can serve as a biomarker for the cells’ migratory capacity in several biological contexts. It can be hypothesized that the statistical mechanics of intra- and extracellular networks may be applied in the future as a powerful tool to explore quantitatively the biomechanical foundation of viscoelasticity over a broad range of time and length scales. Finally, the importance of the cellular viscoelasticity is illustrated in identifying and characterizing multiple disorders, such as cancer, tissue injuries, acute or chronic inflammations or fibrotic diseases.

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Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer

Cited by 21 publications

References 62 publications

Identification of a Four-Gene-Based SERM Signature for Prognostic and Drug Sensitivity Prediction in Gastric Cancer

Identification of a Four-Gene-Based SERM Signature for Prognostic and Drug Sensitivity Prediction in Gastric Cancer

Pan-Cancer Analyses Reveal Oncogenic and Immunological Role of PLOD2

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

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