Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer
Abstract Background Lung cancer is a major cause of cancer‐related mortality worldwide, with a 5‐year survival rate of approximately 22%. Cisplatin is one of the standard first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC), but its efficacy is often limited by the development o...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1970 |
| _version_ | 1797292574805852160 |
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| author | Somayeh Hashemi Sheikhshabani Paratoo Modarres Soudeh Ghafouri‐Fard Zeinab Amini‐Farsani Lavin Khodaee Nasibeh Shaygan Zahra Amini‐Farsani Mir Davood Omrani |
| author_facet | Somayeh Hashemi Sheikhshabani Paratoo Modarres Soudeh Ghafouri‐Fard Zeinab Amini‐Farsani Lavin Khodaee Nasibeh Shaygan Zahra Amini‐Farsani Mir Davood Omrani |
| author_sort | Somayeh Hashemi Sheikhshabani |
| collection | DOAJ |
| description | Abstract Background Lung cancer is a major cause of cancer‐related mortality worldwide, with a 5‐year survival rate of approximately 22%. Cisplatin is one of the standard first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC), but its efficacy is often limited by the development of resistance. Despite extensive research on the molecular mechanisms of chemoresistance, the underlying causes remain elusive and complex. Aims We analyzed three microarray datasets to find the gene signature and key pathways related to cisplatin resistance in NSCLC. Methods and Results We compared the gene expression of sensitive and resistant NSCLC cell lines treated with cisplatin. We found 274 DEGs, including 111 upregulated and 163 downregulated genes, in the resistant group. Gene set enrichment analysis showed the potential roles of several DEGs, such as TUBB2B, MAPK7, TUBAL3, MAP2K5, SMUG1, NTHL1, PARP3, NTRK1, G6PD, PDK1, HEY1, YTHDF2, CD274, and MAGEA1, in cisplatin resistance. Functional analysis revealed the involvement of pathways, such as gap junction, base excision repair, central carbon metabolism, and Notch signaling in the resistant cell lines. Conclusion We identified several molecular factors that contribute to cisplatin resistance in NSCLC cell lines, involving genes and pathways that regulate gap junction communication, DNA damage repair, ROS balance, EMT induction, and stemness maintenance. These genes and pathways could be targets for future studies to overcome cisplatin resistance in NSCLC. |
| first_indexed | 2024-03-07T19:58:26Z |
| format | Article |
| id | doaj.art-d0c941ba81cb4ca596f1ea198fbbd37b |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-07T19:58:26Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-d0c941ba81cb4ca596f1ea198fbbd37b2024-02-28T13:54:58ZengWileyCancer Reports2573-83482024-02-0172n/an/a10.1002/cnr2.1970Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancerSomayeh Hashemi Sheikhshabani0Paratoo Modarres1Soudeh Ghafouri‐Fard2Zeinab Amini‐Farsani3Lavin Khodaee4Nasibeh Shaygan5Zahra Amini‐Farsani6Mir Davood Omrani7Student Research Committee, Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology University of Isfahan Isfahan IranDepartment of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Biotechnology and Plant Breeding Islamic Azad University Science and Research Branch Tehran IranDepartment of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran IranBayesian Imaging and Spatial Statistics Group, Institute of Statistics Ludwig‐Maximilian‐Universität München Munich GermanyUrogenital Stem Cell Research Center Shahid Beheshti University of Medical Sciences Tehran IranAbstract Background Lung cancer is a major cause of cancer‐related mortality worldwide, with a 5‐year survival rate of approximately 22%. Cisplatin is one of the standard first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC), but its efficacy is often limited by the development of resistance. Despite extensive research on the molecular mechanisms of chemoresistance, the underlying causes remain elusive and complex. Aims We analyzed three microarray datasets to find the gene signature and key pathways related to cisplatin resistance in NSCLC. Methods and Results We compared the gene expression of sensitive and resistant NSCLC cell lines treated with cisplatin. We found 274 DEGs, including 111 upregulated and 163 downregulated genes, in the resistant group. Gene set enrichment analysis showed the potential roles of several DEGs, such as TUBB2B, MAPK7, TUBAL3, MAP2K5, SMUG1, NTHL1, PARP3, NTRK1, G6PD, PDK1, HEY1, YTHDF2, CD274, and MAGEA1, in cisplatin resistance. Functional analysis revealed the involvement of pathways, such as gap junction, base excision repair, central carbon metabolism, and Notch signaling in the resistant cell lines. Conclusion We identified several molecular factors that contribute to cisplatin resistance in NSCLC cell lines, involving genes and pathways that regulate gap junction communication, DNA damage repair, ROS balance, EMT induction, and stemness maintenance. These genes and pathways could be targets for future studies to overcome cisplatin resistance in NSCLC.https://doi.org/10.1002/cnr2.1970BERcisplatin resistanceEMTmicroarraynon‐small cell lung cancerPARP3 |
| spellingShingle | Somayeh Hashemi Sheikhshabani Paratoo Modarres Soudeh Ghafouri‐Fard Zeinab Amini‐Farsani Lavin Khodaee Nasibeh Shaygan Zahra Amini‐Farsani Mir Davood Omrani Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer Cancer Reports BER cisplatin resistance EMT microarray non‐small cell lung cancer PARP3 |
| title | Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer |
| title_full | Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer |
| title_fullStr | Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer |
| title_full_unstemmed | Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer |
| title_short | Meta‐analysis of microarray data to determine gene indicators involved in cisplatin resistance in non‐small cell lung cancer |
| title_sort | meta analysis of microarray data to determine gene indicators involved in cisplatin resistance in non small cell lung cancer |
| topic | BER cisplatin resistance EMT microarray non‐small cell lung cancer PARP3 |
| url | https://doi.org/10.1002/cnr2.1970 |
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