Clinicopathological Significance of CDKN2A Promoter Hypermethylation Frequency with Pancreatic Cancer
Open accessAbstract
The prognosis of pancreatic cancer patients is very poor, with a 5-year survival of less than 6%. Previous studies demonstrated that the loss of function of CDKN2A is mainly caused by the hypermethylation of CDKN2A gene promoter; however, whether or not it is associated with the incidence of pancreatic cancer still remains unclear. In this study, we systematically reviewed the association between CDKN2A promoter methylation and pancreatic cancer using meta-analysis methods. The pooled data were analyzed by Review Manager 5.2. Fourteen studies eligible studies, including 418 pancreatic cancer, 155 pancreatic intraepithelial neoplasia (PanINs) and 45 chronic pancreatitis (CP) patients were analyzed. We observed that the frequency of CDKN2A methylation was significantly higher in pancreatic cancer patients than in normal healthy controls, the pooled OR = 17.19, 95% CI = 8.72–33.86, P < 0.00001. The frequency of CDKN2A methylation was also significantly higher in PanINs patients than that in normal individual controls, OR = 12.35, 95% CI = 1.70–89.89, P = 0.01. In addition, CDKN2A methylation was associated with worse survival in pancreatic cancer, HR = 4.46, 95% CI = 1.37–14.53, P = 0.01. The results strongly suggest that CDKN2A methylation is correlated with an increased risk of pancreatic cancer. CDKN2A methylation plays a critical role in pancreatic carcinogenesis and may serve as a prognostic marker.
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CDKN2A methylation is associated with different types of pancreatic cancers, including PDAC and PNET, and correlates with shorter overall survival in both PNET and PDAC.
“The methylation is associated with different types of pancreatic cancers, including pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNET), correlating with shorter overall survival in both PNET and PDAC [50].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [50]
The Results (CDKN2A methylation and clinicopathological features; page unavailable) report elevated methylation frequency in both pancreatic ductal adenocarcinoma (PDA) and pancreatic endocrine neoplasms (PENs). The prognostic Results associate methylation with shorter overall survival in PENs and in pancreatic cancer overall, but do not establish that survival association separately for PDA. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCDKN2A mutations and methylation play a crucial role in pancreatic cancer pathogenesis.
“CDKN2A mutations and methylation play a crucial role in pancreatic cancer pathogenesis.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [50]
Higher CDKN2A methylation is observed in pancreatic cancer patients, making it a potential diagnostic tool, particularly in blood, pancreatic tissue and juice samples.
“Higher CDKN2A methylation is observed in pancreatic cancer patients, making it a potential diagnostic tool, particularly when analyzed in blood, pancreatic tissue and juice samples.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [50]
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Cites
Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679 · see citing works
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836 · see citing works
Cancer genes and the pathways they control
Vogelstein, B., & Kinzler, K. W. (2004) · Nature Medicine · doi:10.1038/nm1087 · Cited by 4,245 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
Almoguera, C., Shibata, D. K., Forrester, K., Wj, M., Arnheim, N., & Perucho, M. (1988) · Cell · doi:10.1016/0092-8674(88)90571-5 · Cited by 2,100 · see citing works
Genome Regulation by Polycomb and Trithorax Proteins
Schuettengruber, B., Chourrout, D. M., Vervoort, M., Leblanc, B., & Cavalli, G. (2007) · Cell · doi:10.1016/j.cell.2007.02.009 · Cited by 1,433 · see citing works
Understanding and using sensitivity, specificity and predictive values
Parikh, R. S., Mathai, A., Parikh, S. R., Sekhar, G. C., & Thomas, R. (2008) · Indian Journal of Ophthalmology · doi:10.4103/0301-4738.37595 · Cited by 1,404 · see citing works
Advanced pancreatic carcinoma: current treatment and future challenges
Stathis, A., & Moore, M. J. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.236 · Cited by 791 · see citing works
The Behaviour of 5-Hydroxymethylcytosine in Bisulfite Sequencing
Huang, Y., Pastor, W., Shen, Y.-H., Tahiliani, M., Liu, D. R., & Rao, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008888 · Cited by 755 · see citing works
Long-Term Survival After Pancreatoduodenectomy for Pancreatic Adenocarcinoma
Schnelldorfer, T., Ware, A. L., Sarr, M. G., Smyrk, T. C., Zhang, L., Qin, R., Gullerud, R. E., Donohue, J. H., Nagorney, D. M., & Farnell, M. B. (2008) · Annals of Surgery · doi:10.1097/sla.0b013e3181613142 · Cited by 457 · see citing works
MicroRNA-21 is Overexpressed in Pancreatic Cancer and a Potential Predictor of Survival
Dillhoff, M. E., Liu, J., Frankel, W. L., Croce, C. M., & Bloomston, M. (2008) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-008-0584-x · Cited by 409 · see citing works
von Burstin, J., Eser, S., Paul, M. C., Seidler, B., Brandl, M., Messer, M., von Werder, A., Schmidt, A., Mages, J., Pagel, P., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.004 · Cited by 356 · see citing works
Moriyama, T., Ohuchida, K., Mizumoto, K., Yu, J., Sato, N., Nabae, T., Takahata, S., Toma, H., Nagai, E., & Tanaka, M. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0592 · Cited by 342 · see citing works
Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K., Wilentz, R. E., Yeo, C. J., Hruban, R. H., & Goggins, M. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61104-2 · Cited by 225 · see citing works
DNA Methylation Alterations in the Pancreatic Juice of Patients with Suspected Pancreatic Disease
Matsubayashi, H., Canto, M. I., Sato, N., Klein, A. P., Abe, T., Yamashita, K., Yeo, C. J., Kalloo, A. N., Hruban, R. H., & Goggins, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2664 · Cited by 213 · see citing works
Moore, P. S., Orlandini, S., Zamboni, G., Capelli, P., Rigaud, G., Falconi, M., Bassi, C., Lemoine, N. R., & Scarpa, A. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2000.1567 · Cited by 197 · see citing works
CpG island methylation in carcinoid and pancreatic endocrine tumors
Chan, A. O. O., Kim, S. G., Bedeir, A., Issa, J. J., Hamilton, S. R., & Rashid, A. (2003) · Oncogene · doi:10.1038/sj.onc.1206123 · Cited by 180 · see citing works
Aberrant Hypermethylation of Tumor Suppressor Genes in Pancreatic Endocrine Neoplasms
House, M. G., Herman, J. G., Guo, M. Z., Hooker, C. M., Schulick, R. D., Lillemoe, K. D., Cameron, J. L., Hruban, R. H., Maitra, A., & Yeo, C. J. (2003) · Annals of Surgery · doi:10.1097/01.sla.0000086659.49569.9e · Cited by 178 · see citing works
Iacobuzio–Donahue, C. A. (2011) · Gut · doi:10.1136/gut.2010.236026 · Cited by 158 · see citing works
Peng, D., Kanai, Y., Sawada, M., Ushijima, S., Hiraoka, N., Kitazawa, S., & Hirohashi, S. (2006) · Carcinogenesis · doi:10.1093/carcin/bgi361 · Cited by 155 · see citing works
Tan, S., Ida, H., Lau, Q. C., Goh, B.-C., Chieng, W.-S., Loh, M. C. S., & Ito, Y. (2007) · Oncology Reports · doi:10.3892/or.18.5.1225 · Cited by 137 · see citing works
Genetic Mutations Associated with Cigarette Smoking in Pancreatic Cancer
Blackford, A. L., Parmigiani, G., Kensler, T. W., Wolfgang, C. L., Jones, S., Zhang, X., Parsons, D. W., Lin, J., Leary, R. J., Eshleman, J. R., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0015 · Cited by 134 · see citing works
Cystic Pancreatic Neuroendocrine Tumors
Singhi, A. D., Chu, L. C. H., Tatsas, A. D., Shi, C., Ellison, T. A., Fishman, E. K., Kawamoto, S., Schulick, R. D., Wolfgang, C. L., Hruban, R. H., et al. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e31826a0048 · Cited by 134 · see citing works
Methods of DNA methylation analysis
Shen, L., & Waterland, R. A. (2007) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3282bf6f43 · Cited by 131 · see citing works
Therapeutic options for the management of pancreatic cancer
Rossi, M. L. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i32.11142 · Cited by 129 · see citing works
Molecular Analysis to Detect Pancreatic Ductal Adenocarcinoma in High-Risk Groups
Yan, L., McFaul, C., Howes, N., Leslie, J., Lancaster, G., Wong, T., Threadgold, J., Evans, J. E., Gilmore, I. T., Smart, H. L., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.006 · Cited by 117 · see citing works
Diagnosing Pancreatic Cancer Using Methylation Specific PCR Analysis
Fukushima, N., Walter, K., Ueki, T., Sato, N., Matsubayashi, H., Cameron, J. L., Hruban, R. H., Canto, M. I., Yeo, C. J., & Goggins, M. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.183 · Cited by 103 · see citing works
Cystic Pancreatic Neuroendocrine Tumors
Ahrendt, S. A., KOMOROWSKI, R. A., Demeure, M. J., Wilson, S. D., & Pitt, H. A. (2002) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(01)00020-8 · Cited by 103 · see citing works
Liu, L., Broaddus, R. R., Yao, J. C., Xie, S.-S., White, J. A., Wu, T., Hamilton, S. R., & Rashid, A. (2005) · Modern Pathology · doi:10.1038/modpathol.3800490 · Cited by 102 · see citing works
Epigenetics and pancreatic cancer: Pathophysiology and novel treatment aspects
Neureiter, D. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i24.7830 · Cited by 98 · see citing works
Jiao, L., Zhu, J., Hassan, M. M., Evans, D. B., Abbruzzese, J. L., & Li, D. (2006) · Pancreas · doi:10.1097/01.mpa.0000246665.68869.d4 · Cited by 96 · see citing works
Baumgart, S., Glesel, E., Singh, G., Chen, N., Reutlinger, K., Zhang, J., Billadeau, D. D., Fernández-Zapico, M. E., Gress, T. M., Singh, S. K., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.11.001 · Cited by 96 · see citing works
p16INK4a is a Prognostic Marker in Resected Ductal Pancreatic Cancer
Gerdes, B., Ramaswamy, A., Ziegler, A., Lang, S. A., Kersting, M., Baumann, R., Wild, A., Moll, R., Rothmund, Μ., & Bartsch, D. K. (2002) · Annals of Surgery · doi:10.1097/00000658-200201000-00007 · Cited by 89 · see citing works
Zhao, S., Venkatasubbarao, K., Li, S., & Freeman, J. W. (2003) · PubMed · Cited by 84 · see citing works
Precancerous lesions of the pancreas
Zamboni, G., Hirabayashi, K., Castelli, P., & Lennon, A. M. (2013) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2013.04.001 · Cited by 81 · see citing works
Boninsegna, L., Partelli, S., D’Innocenzio, M. M., Capelli, P., Scarpa, A., Bassi, C., Pederzoli, P., & Falconi, M. (2010) · Neuroendocrinology · doi:10.1159/000318771 · Cited by 73 · see citing works
El‐Maarri, O. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.6.e25 · Cited by 73 · see citing works
Koh, Y. X., Chok, A. Y., Zheng, H., Tan, C. S., & Goh, B. K. P. (2014) · Surgery · doi:10.1016/j.surg.2014.03.026 · Cited by 71 · see citing works
Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions
Klump, B., Hsieh, C. ‐., Nehls, O., Dette, S., Holzmann, K., Kießlich, R., Jung, M. F., Sinn, U., Ortner, M., Porschen, R., et al. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600734 · Cited by 51 · see citing works
Tumor-Suppressing Pathways in Cystic Pancreatic Tumors
Gerdes, B., Wild, A., Wittenberg, J., Barth, P. J., Ramaswamy, A., Kersting, M., Lüttges, J., Klöppel, G., & Bartsch, D. K. (2003) · Pancreas · doi:10.1097/00006676-200301000-00008 · Cited by 45 · see citing works
Daukša, A., Gulbinas, A., Barauskas, G., Pundzius, J., Oldenburg, J., & El‐Maarri, O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037509 · Cited by 38 · see citing works
p16INK4a alterations in chronic pancreatitis—indicator for high-risk lesions for pancreatic cancer
Gerdes, B., Ramaswamy, A., Kersting, M., Ernst, M. E., Lang, S. A., Schuermann, M., Wild, A., & Bartsch, D. K. (2001) · Surgery · doi:10.1067/msy.2001.112071 · Cited by 37 · see citing works
Epigenetic targeting in pancreatic cancer
van Kampen, J. G. M., Zanten, M. M. V., Simmer, F., van der Graaf, W. T. A., Ligtenberg, M. J. L., & Nagtegaal, I. D. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2013.12.002 · Cited by 36 · see citing works
El‐Maarri, O. (2004) · Humana Press eBooks · doi:10.1385/1-59259-828-5:195 · Cited by 29 · see citing works
Reduced levels of p15INK4b, p16INK4a, p21cip1 and p27kip1 in pancreatic carcinoma
Li, G., Ji, Y., Liu, C., Li, J., & Zhou, Y. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.771 · Cited by 18 · see citing works
Gerdes, B., Bartsch, D. K., Ramaswamy, A., Kersting, M., Wild, A., Schuermann, M., Frey, M., & Rothmund, Μ. (2000) · Pancreas · doi:10.1097/00006676-200011000-00007 · Cited by 18 · see citing works
Implication of the INK4a/ARF Locus in Gastroenteropancreatic Neuroendocrine Tumorigenesis
Simon, B., & Lubomierski, N. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1294.033 · Cited by 17 · see citing works
Teich, N., & Mössner, J. (2004) · Digestive Diseases · doi:10.1159/000082794 · Cited by 15 · see citing works
Diagnostic accuracy of K-ras mutation for pancreatic carcinoma: a meta-analysis
Liu, S., Chen, G., Zhao, Y.-P., Wu, W., & Zhang, T. (2013) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(13)60073-9 · Cited by 12 · see citing works
Ohtsubo, K., Watanabe, H., Yamaguchi, Y., Hu, Y.-X., Motoo, Y., Okai, T., & Sawabu, N. (2003) · Journal of Gastroenterology · doi:10.1007/s00535-003-1119-6 · Cited by 2 · see citing works
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Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer
Stefanoudakis, D., Frountzas, M., Schizas, D., Michalopoulos, N. V., Drakaki, A., & Toutouzas, K. G. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46040177 · Cited by 110 · see citing works
Chen, Z., Guo, Y., Zhao, D., Zou, Q., Yu, F., Zhang, L., & Xu, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.808208 · Cited by 87 · see citing works
- Authors
- Tang, B., Li, Y., Qi, G., Yuan, S., Wang, Z., Yu, S., Li, B., & He, S.
- Affiliations
- Guilin Medical University (CN)
- Corresponding author
- Tang, Bo
- Venue
- Scientific Reports
- Published
- 2015-09-04
- Volume
- 5
- Issue
- 1
- Pages
- 13563-13563
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4642558
- OpenAlex
- W1222822579
- Cited by
- 64
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30870719, 81160066, No. 81360367, 81360367)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- CDKN2A, promoter hypermethylation, pancreatic cancer, pancreatic intraepithelial neoplasia, chronic pancreatitis, cancer risk, prognostic factors, pancreatic carcinogenesis, DNA methylation
- MeSH terms
- Base Sequence, Female, Gene Frequency, Genetic Markers, Humans, Male, Molecular Sequence Data, Pancreatic Neoplasms, Promoter Regions, Genetic, Risk Factors, Biomarkers, Tumor, Incidence, Survival Rate, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Genetic Predisposition to Disease, Genetic Association Studies
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