Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.

Launching: Thursday 12th December 2024
ADVANCED SEARCH
Log in
Top
Discover Oncology
Published in:

Open Access 01-12-2024 | Colorectal Cancer | Analysis

Exon 1 methylation status of CDH13 is associated with decreased overall survival and distant metastasis in patients with postoperative colorectal cancer

Authors: PengCheng Xiang, PengJu Li, Xiaoqi Yuan, Xiuhao Zhao, Zitian Xiao, Bingguan Chen, Kenwen Liu, Evelyne Bischof, Junyi Han

Published in: Discover Oncology | Issue 1/2024

Login to get access

Abstract

Background

Cadherin 13 (CDH13) is a member of the cadherin superfamily that exerts tumor-suppressive effects on cancers derived from epithelial cells. Although hypermethylation of CDH13 promoter has been reported in various cancers, its prognostic value for colorectal cancer (CRC) is still controversial. The methylation alterations of CDH13 within exon 1 have not yet been investigated.

Methods

A total of 49 CRC patients were recruited for the prospective study. The methylation status of CpG sites was quantified by Bisulfite Amplicon Sequencing (BSAS) in malignant tissues and adjacent normal tissues. The primary endpoint of the study was overall survival (OS) after surgery. The relationship between methylation level with pathological stage and OS was also evaluated.

Results

Compared with adjacent normal tissues, the overall average methylation level within exon 1 was significantly increased in tumor tissues (p < 0.001). The association study showed that the hypermethylation status of the CpG1 site was non-significantly associated with the presence of distant metastasis (p = 0.032). Moreover, the hypermethylation of two CpG sites, including CpG1 (p = 0.003) and CpG5 (p = 0.032), was associated with worse OS in CRC. Co-hypermethylation of CpG1 and CpG5 sites was significantly associated with a worse clinical outcome (HR: 4.43 [95% CI 1.27–15.46]; p = 0.019) in multivariate Cox regression analysis.

Conclusion

The methylation level of CDH13 exon 1 in CRC tissue was significantly higher than in adjacent normal tissues. Hypermethylation at the CpG1 site suggests a risk of distant metastasis in CRC. The hypermethylation of the CpG1 site and CpG5 site, including the co-hypermethylation of these two sites, may serve as a valuable prognostic biomarker.
Literature
1.
Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin. 2018;68(6):394–424.CrossRef
2.
Van Cutsem E, et al. Binimetinib, encorafenib, and cetuximab triplet therapy for patients with BRAF V600E-mutant metastatic colorectal cancer: safety lead-in results from the phase III BEACON colorectal cancer study. J Clin Oncol. 2019;37(17):1460–9.CrossRefPubMedPubMedCentral
3.
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3(6):415–28.CrossRefPubMed
4.
Jordà M, Peinado MA. Methods for DNA methylation analysis and applications in colon cancer. Mutat Res. 2010;693(1–2):84–93.CrossRefPubMed
5.
Tan J, et al. Hypermethylation of CpG islands is more prevalent than hypomethylation across the entire genome in breast carcinogenesis. Clin Exp Med. 2013;13(1):1–9.CrossRefPubMed
6.
7.
Zhang X, et al. Promoter hypermethylation of CHODL contributes to carcinogenesis and indicates poor survival in patients with early-stage colorectal cancer. J Cancer. 2020;11(10):2874–86.CrossRefPubMedPubMedCentral
8.
Chang SC, et al. Hypermethylation and decreased expression of TMEM240 are potential early-onset biomarkers for colorectal cancer detection, poor prognosis, and early recurrence prediction. Clin Epigenetics. 2020;12(1):67.CrossRefPubMedPubMedCentral
9.
Moelans CB, Verschuur-Maes AH, van Diest PJ. Frequent promoter hypermethylation of BRCA2, CDH13, MSH6, PAX5, PAX6 and WT1 in ductal carcinoma in situ and invasive breast cancer. J Pathol. 2011;225(2):222–31.CrossRefPubMed
10.
11.
Yuan XD, et al. Methylation status of the T-cadherin gene promotor in peripheral blood mononuclear cells is associated with HBV-related hepatocellular carcinoma progression. Pathol Res Pract. 2020;216(5): 152914.CrossRefPubMed
12.
13.
Esteller M, et al. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61(8):3225–9.PubMed
14.
Toyooka S, et al. Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas. Cancer Res. 2002;62(12):3382–6.PubMed
15.
16.
Xu XL, et al. Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis. World J Gastroenterol. 2004;10(23):3441–54.CrossRefPubMedPubMedCentral
17.
Hibi K, et al. Aberrant methylation of HLTF, SOCS-1, and CDH13 genes is shown in colorectal cancers without lymph node metastasis. Dis Colon Rectum. 2005;48(6):1282–6.CrossRefPubMed
18.
Wang Z, et al. CDH13 and FLBN3 gene methylation are associated with poor prognosis in colorectal cancer. Pathol Oncol Res. 2012;18(2):263–70.CrossRefPubMed
19.
Duan BS, Xie LF, Wang Y. Aberrant methylation of T-cadherin can be a diagnostic biomarker for colorectal cancer. Cancer Gen Prot. 2017;14(4):277–84.
20.
Ozer B, Sezerman U. Analysis of the interplay between methylation and expression reveals its potential role in cancer aetiology. Funct Integr Genomics. 2017;17(1):53–68.CrossRefPubMed
21.
22.
23.
24.
Dmitrijeva M, et al. Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates. Nucleic Acids Res. 2018;46(14):7022–39.CrossRefPubMedPubMedCentral
25.
Dugué PA, et al. DNA methylation-based biological aging and cancer risk and survival: pooled analysis of seven prospective studies. Int J Cancer. 2018;142(8):1611–9.CrossRefPubMed
26.
Hsu CH, et al. Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan. World J Gastroenterol. 2020;26(2):154–67.CrossRefPubMedPubMedCentral
27.
Huang Q, et al. Screening of exon methylation biomarkers for colorectal cancer via LC-MS/MS strategy. J Mass Spectrom. 2017;52(12):860–6.CrossRefPubMed
28.
Jäkel C, et al. Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability. Nat Commun. 2017;8(1):1323.CrossRefPubMedPubMedCentral
29.
Sharma P, et al. Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease. Tumour Biol. 2016;37(11):14687–99.CrossRefPubMed
30.
Li X, et al. The prognostic value of DAPK1 hypermethylation in gliomas: a site-specific analysis. Pathol Res Pract. 2018;214(7):940–8.CrossRefPubMed
31.
32.
Zhang Y, et al. DNA methylation analysis by bisulfite conversion, cloning, and sequencing of individual clones. Methods Mol Biol. 2009;507:177–87.CrossRefPubMed
33.
Xue W, et al. Genome-wide methylation analysis identifies novel prognostic methylation markers in colon adenocarcinoma. Biomed Pharmacother. 2018;108:288–96.CrossRefPubMed
34.
Wang N, et al. Site-specific hypermethylation of RUNX3 predicts poor prognosis in gastric cancer. Arch Med Res. 2016;47(4):285–92.CrossRefPubMed
35.
You W, et al. Clinical Significances of positive postoperative serum CEA and post-preoperative CEA increment in stage II and III colorectal cancer: a multicenter retrospective study. Front Oncol. 2020;10:671.CrossRefPubMedPubMedCentral
36.
Abasse Kassim S, et al. Clinicopathologic and epidemiological characteristics of prognostic factors in post-surgical survival of colorectal cancer patients in Jiangsu Province. China Cancer Epidemiol. 2019;62: 101565.CrossRefPubMed
Metadata
Title
Exon 1 methylation status of CDH13 is associated with decreased overall survival and distant metastasis in patients with postoperative colorectal cancer
Authors
PengCheng Xiang
PengJu Li
Xiaoqi Yuan
Xiuhao Zhao
Zitian Xiao
Bingguan Chen
Kenwen Liu
Evelyne Bischof
Junyi Han
Publication date
01-12-2024
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-024-01604-x

Other articles of this Issue 1/2024

Intratumoral microbiota of pancreatic ductal adenocarcinoma impact patient prognosis by influencing tumor microenvironment

Unraveling molecular signatures and prognostic biomarkers in glioblastoma: a comprehensive study on treatment resistance and personalized strategies

Polyamines: the pivotal amines in influencing the tumor microenvironment

  • Open Access
  • Review

SLITRK2 as a prognostic and immunological biomarker in gastric cancer

Research trends of bone tumor treatment with 3D printing technology from 2013 to 2022: a bibliometric analysis

  • Open Access
  • Research

Efficacy and safety of lenalidomide in the treatment of B-cell non-Hodgkin lymphoma

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the broader systemic effects of menopause, so you can help patients in your clinics through the transition.

Launching: Thursday 12th December 2024
 

Prof. Martha Hickey
Dr. Claudia Barth
Dr. Samar El Khoudary
Developed by: Springer Medicine
Register your interest now

Keynote webinar | Spotlight on adolescent vaping

  • Live
  • Webinar | 29-01-2025 | 18:00 (CET)

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Watch it live: Wednesday 29th January, 18:00-19:30 CET
 

Prof. Ann McNeill
Dr. Debbie Robson
Benji Horwell
Developed by: Springer Medicine
Join the webinar

Keynote webinar | Spotlight on modern management of frailty

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft
Prof. Barbara C. van Munster
Prof. Mirko Petrovic
Developed by: Springer Medicine
Watch now

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more
Image Credits