Abstract
Objective
To investigate the association between KiSS-1 methylation and clinicopathological characteristics of gastric cancer and evaluate the role of peritoneal lavage fluid in detecting peritoneal metastases.
Methods
The methylation status of KiSS-1 gene in 40 gastric cancer specimens, the corresponding adjacent normal mucosa, lymph nodes and peritoneal lavage fluid was investigated by methylation-spcific polymerase chain reaction(MS-PCR).
Results
Aberrant methylation of KiSS-1 gene was detected in 55%(22/40) of the adjacent normal mucosa, 82.5% (33/40)of gastric cancer specimens, 80.95%(17/21) of the lymph nodes, and 42.5%(17/40) of peritoneal lavage fluid. Methylation in gastric carcinoma and lymphonode was more frequent than in non-neoplastic gastiric mucosa. Presence of KiSS-1 methylation in peritoneal lavage fluid was significantly correlated with tumor invasion (P=0.043). The accuracy of KiSS-1 methylation in peritoneal lavage fluid for diagnosing peritoneal metastasis was 70%, with a sensitivity of 77.8% and a specificity of 67.7%.
Conclusion
Aberrant methylation of KiSS-1 gene is a common event in the occurrence and progression of gastric carcinoma, which may provide useful information for the early diagnosis of peritoneal metastases and a new therapy for gastric cancer.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin 2005; 55: 74–108.
Ushijima T, Sasako M. Focus on gastric cancer[J]. Cancer Cell 2004; 5: 121–125.
Herman JG, Bsylin SB. Gene silencing in cancer in association with promoter hypermethylation[J]. N Engl J Med 2003; 349: 2042–2054.
Oliveira C, Velho S, Domingo E, et al. Concomitant RASSF1A hypermethylation and KRAS/BRAF mutations occur preferentially in MSI sporadic colorectal cancer[J]. Oncogene 2005; 24: 7630–7634.
Shen WJ, Dai DQ, Teng Y, et al. Regulation of demethylation and re-expression of RASSF1A gene in gastric cancer cell lines by combined treatment of 5-Aza-CdR and NaB[J]. World J Gastroenterol 2008; 14: 595–600.
Kang GH, Shim YH, Jung HY, et al. CpG island methylation in premalignant stages of gastric carcinoma[J]. Cancer Res 2001; 61: 2847–2851.
Yamashita S, Tsujino Y, Moriguchi K, et al. Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2′ -deoxycytidine treatment and oligonucleotide microarry[J]. Cancer Sci 2006; 97: 64–71.
Katsuragi K, Yashiro M, Sawada T, et al. Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection[J]. Br J Cancer 2007; 97: 550–556.
Kamiyama H, Noda H, Takata O, et al. Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer[J]. J Surg Oncol 2009; 100: 69–74.
Shirasaki F, Takata M, Hatta N, et al. Loss of expression of the metastasis suppressor gene KiSS1 during melanoma progression and its association with LOH of chromosome 6q16.3–q23[J]. Cancer Res 2001; 61: 7422–7425.
Stark AM, Tongers K, Maass N, et al. Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases[J]. J Cancer Res Clin Oncol 2005; 131: 191–198.
Yi X, Li CY, Zhang SH, et al. Relationship and clinical significance of KiSS-1, nuclear factor kappa B (NF-kappaB), p50, and matrix metalloproteinase 9 expression in breast cancer[J]. Zhonghua Bing Li Xue Za Zhi(in Chinese) 2008; 37: 238–242.
Ringel MD, Hardy E, Bernet VJ, et al. Metastin receptor is ov erexpressed in papillary thyroid cancer and activates MAP Kinase in thyroid cancer cells[J]. J Clin Endocrinol Metab 2002, 87: 2399–2402.
Li N, Li SS, Zhang HY, et al. Effect of KISS-1 on invasive potential and proliferation of esophageal squamous carcinoma cell line EC-1[J]. Zhonghua Bing Li Xue Za Zhi (in Chinese) 2009; 38: 263–267.
Guan-Zhen Y, Ying C, Can-Rong N, et al. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer[J]. Int J Exp Pathol 2007; 88: 175–183.
Nagai K, Doi R, Katagiri F, et al. Prognostic value of metastin expression in human pancreatic cancer[J]. J Exp Clin Cancer Res 2009; 28: 9.
Belinsky SA. Gene-promoter hypermethylation as a biomarker in lung cancer[J]. Nat Rev Cancer 2004; 4:707–717.
Topaloglu O, Hoque MO, Tokumaru Y, et al. Detection of promoter hypermethylation of multiple genes in the tumor and bronchoalveolar lavage of patients with lung cancer[J]. Clin Cancer Res 2004; 10: 2284–2288.
Hoque MO, Begum S, Topaloglu O, et al. Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer[J]. Cancer Res 2004; 64: 5511–5517.
Carvalho AL, Jeronimo C, Kim MM, et al. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma[J]. Clin Cancer Res 2008; 14: 97–107.
Fackler MJ, Malone K, Zhang Z, et al. Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid[J]. Clin Cancer Res 2006; 12: 3306–3310.
Usadel H, Brabender J, Danenberg KD, et al. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer[J]. Cancer Res 2002; 62: 371–375.
Koike H, Ichikawa D, Ikoma H, et al. Comparison of methylation-specific polymerase chain reaction (MSP) with reverse transcriptase-polymerase chain reaction (RT-PCR) inperipheral blood of gastric cancer patients[J]. J Surg Oncol 2004; 87: 182–186.
Laird PW. The power and the promise of DNA methylation markers[J]. Nat Rev Cancer 2003; 3: 253–266.
Sidransky D. Emerging molecular markers of cancer[J]. Nat Rev Cancer 2002; 2: 210–219.
Miyamoto K, Ushijima T. Diagnostic and therapeutic applications of epigenetics[J]. Jpn J Clin Oncol 2005; 35: 293–301.
Tost J. DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker[J]. Methods Mol Biol 2009; 507: 3–20.
Cottrell SE. Molecular diagnostic applications of DNA methylation technology[J]. Clin Biochem 2004; 37: 595–604.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the National Natural Science Foundation of China, (No. 30572162); and the Science Foundation for High Education Program of Liaoning Province(No. 2008S240)
Rights and permissions
About this article
Cite this article
Yang, Z., Dai, DQ. & Du, YY. Promoter hypermethylation of KiSS-1 gene in gastric cancer. Chin. J. Cancer Res. 22, 280–284 (2010). https://doi.org/10.1007/s11670-010-0280-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11670-010-0280-8