Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index
IntroductionLung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, resea...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1236444/full |
| _version_ | 1797670028223447040 |
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| author | Rihan Wu Rihan Wu Ru Ma Xiaojun Duan Xiaojun Duan Jiandong Zhang Kexin Li Lei Yu Mingyang Zhang Pengxia Liu Changshan Wang |
| author_facet | Rihan Wu Rihan Wu Ru Ma Xiaojun Duan Xiaojun Duan Jiandong Zhang Kexin Li Lei Yu Mingyang Zhang Pengxia Liu Changshan Wang |
| author_sort | Rihan Wu |
| collection | DOAJ |
| description | IntroductionLung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index.MethodsRNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein–protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs.ResultsOverall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index.ConclusionOur study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance. |
| first_indexed | 2024-03-11T20:53:34Z |
| format | Article |
| id | doaj.art-54772d165d8a42a1808ab74c95cbbdfe |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T20:53:34Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-54772d165d8a42a1808ab74c95cbbdfe2023-09-30T21:18:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12364441236444Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem indexRihan Wu0Rihan Wu1Ru Ma2Xiaojun Duan3Xiaojun Duan4Jiandong Zhang5Kexin Li6Lei Yu7Mingyang Zhang8Pengxia Liu9Changshan Wang10School of Life Science, Inner Mongolia University, Hohhot, ChinaThe Department of Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Basic Medicine, Inner Mongolia Medical University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaSchool of Life Science, Inner Mongolia University, Hohhot, ChinaIntroductionLung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index.MethodsRNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein–protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs.ResultsOverall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index.ConclusionOur study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1236444/fullLUSCprognosisbiomarkertumor microenvironmentcancer stem cell |
| spellingShingle | Rihan Wu Rihan Wu Ru Ma Xiaojun Duan Xiaojun Duan Jiandong Zhang Kexin Li Lei Yu Mingyang Zhang Pengxia Liu Changshan Wang Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index Frontiers in Immunology LUSC prognosis biomarker tumor microenvironment cancer stem cell |
| title | Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index |
| title_full | Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index |
| title_fullStr | Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index |
| title_full_unstemmed | Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index |
| title_short | Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index |
| title_sort | identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression immune infiltration and stem index |
| topic | LUSC prognosis biomarker tumor microenvironment cancer stem cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1236444/full |
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