CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer
Abstract Purpose This study aims to investigate the biological roles and molecular mechanisms of Cathepsin G (CTSG) in the progression of non-small cell lung cancer (NSCLC). Methods Western blotting and immunohistochemistry analyses of clinical samples were performed to determine the expression leve...
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| Format: | Article |
| Language: | English |
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Springer
2024-12-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-024-06051-3 |
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| author | Qian Dai Xufeng Yao Yanke Zhang Qian Chai Xueyi Feng Hongbin Zhu Lei Zhao |
| author_facet | Qian Dai Xufeng Yao Yanke Zhang Qian Chai Xueyi Feng Hongbin Zhu Lei Zhao |
| author_sort | Qian Dai |
| collection | DOAJ |
| description | Abstract Purpose This study aims to investigate the biological roles and molecular mechanisms of Cathepsin G (CTSG) in the progression of non-small cell lung cancer (NSCLC). Methods Western blotting and immunohistochemistry analyses of clinical samples were performed to determine the expression levels of CTSG in patients with NSCLC. Bioinformatic analysis of clinical datasets was conducted to evaluate the correlation between CTSG and lymph node metastasis, tumor stage, and immune cell infiltration. Gain-of-function assays and tumor implantation experiments were employed to determine the effects of CTSG on malignant behaviors of NSCLC cells. Transcriptome sequencing and subsequent bioinformatic analysis were performed to explore the signaling pathways regulated by CTSG. Western blotting and qPCR were utilized to assess the influence of CTSG on the MAPK and EMT signaling pathways. Results CTSG is expressed at low levels and serves as a prognostic marker in NSCLC. The downregulation of CTSG expression was associated with lymph node metastasis, tumor stage, and immune cell infiltration. CTSG inhibits NSCLC cell proliferation, migration, and invasion as well as tumor growth in nude mice. There exists a significant correlation between CTSG expression and endoplasmic reticulum function, cell cycling, and the IL-17 signaling pathway. CTSG suppresses the MAPK and EMT signaling pathways in NSCLC cells. Moreover, DNA methylation and histone deacetylation have been identified as crucial mechanisms contributing to the decreased expression of CTSG. Conclusion CTSG inhibits NSCLC development by suppressing the MAPK signaling pathway and is also associated with tumor immunity. |
| format | Article |
| id | doaj-art-d05f3f3d99b44afabe8f596a56fd789c |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-d05f3f3d99b44afabe8f596a56fd789c2025-02-09T12:10:26ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352024-12-01151111510.1007/s00432-024-06051-3CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancerQian Dai0Xufeng Yao1Yanke Zhang2Qian Chai3Xueyi Feng4Hongbin Zhu5Lei Zhao6School of Life Sciences, Anhui Medical UniversitySchool of Life Sciences, Anhui Medical UniversityDepartment of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical UniversitySchool of Life Sciences, Anhui Medical UniversityDepartment of Respiratory Medicine, Chaohu Hospital of Anhui Medical UniversityDepartment of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical UniversityAbstract Purpose This study aims to investigate the biological roles and molecular mechanisms of Cathepsin G (CTSG) in the progression of non-small cell lung cancer (NSCLC). Methods Western blotting and immunohistochemistry analyses of clinical samples were performed to determine the expression levels of CTSG in patients with NSCLC. Bioinformatic analysis of clinical datasets was conducted to evaluate the correlation between CTSG and lymph node metastasis, tumor stage, and immune cell infiltration. Gain-of-function assays and tumor implantation experiments were employed to determine the effects of CTSG on malignant behaviors of NSCLC cells. Transcriptome sequencing and subsequent bioinformatic analysis were performed to explore the signaling pathways regulated by CTSG. Western blotting and qPCR were utilized to assess the influence of CTSG on the MAPK and EMT signaling pathways. Results CTSG is expressed at low levels and serves as a prognostic marker in NSCLC. The downregulation of CTSG expression was associated with lymph node metastasis, tumor stage, and immune cell infiltration. CTSG inhibits NSCLC cell proliferation, migration, and invasion as well as tumor growth in nude mice. There exists a significant correlation between CTSG expression and endoplasmic reticulum function, cell cycling, and the IL-17 signaling pathway. CTSG suppresses the MAPK and EMT signaling pathways in NSCLC cells. Moreover, DNA methylation and histone deacetylation have been identified as crucial mechanisms contributing to the decreased expression of CTSG. Conclusion CTSG inhibits NSCLC development by suppressing the MAPK signaling pathway and is also associated with tumor immunity.https://doi.org/10.1007/s00432-024-06051-3CTSGNSCLCPrognosticBiomarkerMAPK |
| spellingShingle | Qian Dai Xufeng Yao Yanke Zhang Qian Chai Xueyi Feng Hongbin Zhu Lei Zhao CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer Journal of Cancer Research and Clinical Oncology CTSG NSCLC Prognostic Biomarker MAPK |
| title | CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer |
| title_full | CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer |
| title_fullStr | CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer |
| title_full_unstemmed | CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer |
| title_short | CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer |
| title_sort | ctsg is a prognostic marker involved in immune infiltration and inhibits tumor progression though the mapk signaling pathway in non small cell lung cancer |
| topic | CTSG NSCLC Prognostic Biomarker MAPK |
| url | https://doi.org/10.1007/s00432-024-06051-3 |
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