ISSN: 1859 - 2872
Phân tích các biến đổi phân tử của CDKN2A và mối liên quan đến biểu hiện gen trong ung thư phổi không tế bào nhỏ
Main Article Content
Keywords
Ung thư phổi không tế bào nhỏ, CDKN2A, CNV, methyl hóa, TCGA.
Tóm tắt
CDKN2A là gene ức chế khối u quan trọng thường bị bất thường trong ung thư phổi không tế bào nhỏ (NSCLC) thông qua methyl hóa promoter, đột biến gene và biến đổi số lượng bản sao (CNV). Dữ liệu methyl hóa DNA, biểu hiện mRNA, đột biến gene, CNV và thông tin lâm sàng của 831 bệnh nhân NSCLC (459 trường hợp ung thư biểu mô tuyến phổi và 372 trường hợp ung thư biểu mô vảy phổi) được phân tích tích hợp. Kết quả cho thấy mất đoạn sâu có mối liên quan mạnh nhất với giảm biểu hiện mRNA CDKN2A (log2 (raw STAR count + 1)), với trung vị giảm từ 9,86 xuống 4,91 và mức giảm rõ rệt hơn ở ung thư biểu mô vảy phổi so với ung thư biểu mô tuyến phổi. Ngược lại, đột biến CDKN2A không liên quan đến giảm biểu hiện mRNA tương ứng. Tóm lại, các biến đổi phân tử của CDKN2A có mối liên quan khác nhau với mức biểu hiện mRNA trong NSCLC, trong đó mất đoạn sâu liên quan mạnh nhất với giảm biểu hiện CDKN2A và rõ rệt hơn ở LUSC so với LUAD.
Article Details
Các tài liệu tham khảo
1. Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3): 229-263. doi:10.3322/caac.21834
2. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature 553(7689): 446-454. doi:10.1038/nature25183
3. Travis WD, Brambilla E, Nicholson AG et al (2015) The 2015 world health organization classification of lung tumors. J Thorac Oncol 10(9): 1243-1260. doi:10.1097/JTO.0000000000000630
4. Zhao L, Zhou X, Li H, Yin T, Jiang Y (2024) Prognosis of immunotherapy for non-small cell lung cancer with CDKN2A loss of function. J Thorac Dis 16(1): 507-515. doi:10.21037/jtd-23-1017
5. Deng C, Li Z xi, Xie C jun et al (2024) Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment. Hum Genomics 18(1): 55. doi:10.1186/s40246-024-00615-7
6. Feng X, Chang H, Xu Y et al (2025) CDKN2A alternations in non-small cell lung cancer: An evaluation using next-generation sequencing. Pathol - Res Pract 274: 156177. doi:10.1016/j.prp.2025.156177
7. Soltan MA, Alhanshani AA, Shati AA et al (2023) Cyclin dependent kinase inhibitor 2a genetic and epigenetic alterations interfere with several immune components and predict poor clinical outcome. Biomedicines. 11(8): 2254. doi:10.3390/biomedicines11082254
8. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368(6473): 753-756. doi:10.1038/368753a0
9. Merlo A, Herman JG, Mao L, et al (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1(7): 686-692. doi:10.1038/nm0795-686
10. Beroukhim R, Mermel CH, Porter D et al (2010) The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899-905. doi:10.1038/nature08822
11. The Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511(7511): 543-550. doi:10.1038/nature13385
12. Tam KW, Zhang W, Soh J et al (2013) CDKN2A/p16 Inactivation mechanisms and their relationship to smoke exposure and molecular features in non–small-cell lung cancer. J Thorac Oncol 8(11): 1378-1388. doi:10.1097/JTO.0b013e3182a46c0c
13. The Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417): 519-525. doi:10.1038/nature11404
14. Zack TI, Schumacher SE, Carter SL et al (2015) Pan-cancer patterns of somatic copy number alteration. Nat Genet 45(10): 1134-1140. doi:10.1038/ng.2760
15. Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ (2013) Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res 23(2): 217-227. doi:10.1101/gr.140301.112
16. Tuna M, Mills GB, Amos CI (2023) Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma. Neoplasia 45: 100932. doi:10.1016/j.neo.2023.100932
17. Gonçalves PG, Reis RM, Bidinotto LT (2022) Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. Anticancer Res 42(11): 5291-5304. doi:10.21873/anticanres.16036
18. Merlo A, Herman JG, Mao L et al (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1(7): 686-692. doi:10.1038/nm0795-686
19. Belinsky SA, Nikula KJ, Palmisano WA et al (1998) Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci 95(20): 11891-11896. doi:10.1073/pnas.95.20.11891
20. Zöchbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD (2001) Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res 61(1): 249-255.
2. Herbst RS, Morgensztern D, Boshoff C (2018) The biology and management of non-small cell lung cancer. Nature 553(7689): 446-454. doi:10.1038/nature25183
3. Travis WD, Brambilla E, Nicholson AG et al (2015) The 2015 world health organization classification of lung tumors. J Thorac Oncol 10(9): 1243-1260. doi:10.1097/JTO.0000000000000630
4. Zhao L, Zhou X, Li H, Yin T, Jiang Y (2024) Prognosis of immunotherapy for non-small cell lung cancer with CDKN2A loss of function. J Thorac Dis 16(1): 507-515. doi:10.21037/jtd-23-1017
5. Deng C, Li Z xi, Xie C jun et al (2024) Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment. Hum Genomics 18(1): 55. doi:10.1186/s40246-024-00615-7
6. Feng X, Chang H, Xu Y et al (2025) CDKN2A alternations in non-small cell lung cancer: An evaluation using next-generation sequencing. Pathol - Res Pract 274: 156177. doi:10.1016/j.prp.2025.156177
7. Soltan MA, Alhanshani AA, Shati AA et al (2023) Cyclin dependent kinase inhibitor 2a genetic and epigenetic alterations interfere with several immune components and predict poor clinical outcome. Biomedicines. 11(8): 2254. doi:10.3390/biomedicines11082254
8. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368(6473): 753-756. doi:10.1038/368753a0
9. Merlo A, Herman JG, Mao L, et al (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1(7): 686-692. doi:10.1038/nm0795-686
10. Beroukhim R, Mermel CH, Porter D et al (2010) The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899-905. doi:10.1038/nature08822
11. The Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511(7511): 543-550. doi:10.1038/nature13385
12. Tam KW, Zhang W, Soh J et al (2013) CDKN2A/p16 Inactivation mechanisms and their relationship to smoke exposure and molecular features in non–small-cell lung cancer. J Thorac Oncol 8(11): 1378-1388. doi:10.1097/JTO.0b013e3182a46c0c
13. The Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417): 519-525. doi:10.1038/nature11404
14. Zack TI, Schumacher SE, Carter SL et al (2015) Pan-cancer patterns of somatic copy number alteration. Nat Genet 45(10): 1134-1140. doi:10.1038/ng.2760
15. Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ (2013) Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res 23(2): 217-227. doi:10.1101/gr.140301.112
16. Tuna M, Mills GB, Amos CI (2023) Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma. Neoplasia 45: 100932. doi:10.1016/j.neo.2023.100932
17. Gonçalves PG, Reis RM, Bidinotto LT (2022) Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. Anticancer Res 42(11): 5291-5304. doi:10.21873/anticanres.16036
18. Merlo A, Herman JG, Mao L et al (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1(7): 686-692. doi:10.1038/nm0795-686
19. Belinsky SA, Nikula KJ, Palmisano WA et al (1998) Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci 95(20): 11891-11896. doi:10.1073/pnas.95.20.11891
20. Zöchbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD (2001) Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res 61(1): 249-255.