The value of serum RASSF10 hypermethylation as a diagnostic and prognostic tool for gastric cancer
The tumor-suppressing role of Ras-association domain family 10 (RASSF10) has been described in several types of cancers. Here, we evaluated the potential use of the hypermethylation status of the RASSF10 promoter in serum as a new diagnostic and prognostic tool in gastric cancer (GC). We used bisulfite sequencing polymerase chain reaction to examine RASSF10 methylation levels in serum and/or tumor samples from 82 GC, 45 chronic atrophic gastritis (CAG), and 50 healthy control patients. In the serum of GC patients, the median level of RASSF10 methylation was higher at 47.84 % than those in the serum of CAG and healthy control patients at 11.89 and 11.35 %, respectively. The median level of RASSF10 methylation in GC tumor tissue was similarly high at 62.70 %. Furthermore, RASSF10 methylation levels were highly correlated between paired serum and tumor samples from GC patients. We performed receiver-operating characteristic curve analyses to verify that serum RASSF10 methylation levels could effectively distinguish GC from control patients. Moreover, multivariate analyses showed that high serum RASSF10 methylation levels in GC patients were associated with large tumors, lymph node metastasis, and high carcinoembryonic antigen (CEA) levels. Survival analyses showed that GC patients with high serum RASSF10 methylation levels had shorter overall and disease-free survival after D2 lymphadenectomy than those with low levels. High serum RASSF10 methylation levels were also an independent predictor of tumor recurrence and GC patient survival. In conclusion, serum RASSF10 promoter methylation levels can serve as a valuable indicator for the diagnosis and prognosis of GC in the clinic.
KeywordsRASSF10 Gastric cancer Serum Hypermethylation Diagnosis Prognosis
This work was supported by the National Natural Science Foundation of China (No. 81000984), the Six Talent Peaks Project of the Jiangsu Province (2011-WS066), and the Social Undertakings of Science and Technology Innovation and Demonstration Project of Nantong City (HS2014042).
Compliance with ethical standards
All procedures were approved by the Human Research Ethics Committee at the Affiliated Hospital of Nantong University, and written informed consent was obtained from all patients before obtaining the serum and/or tumor samples.
Conflicts of interest
- 2.Feng L, Yao C, Li P, Feng Y, Wang F, Liu YF, Guo YB, Mao QS, Xue WJ. Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer. Tumour Biol 2016Google Scholar
- 6.Oba K, Paoletti X, Alberts S, Bang YJ, Benedetti J, Bleiberg H, Catalano P, Lordick F, Michiels S, Morita S, Ohashi Y, Pignon JP, Rougier P, Sasako M, Sakamoto J, Sargent D, Shitara K, Cutsem EV, Buyse M, Burzykowski T, group G: Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis. J Natl Cancer Inst 2013;105:1600–1607Google Scholar
- 23.Li X, Liang Q, Liu W, Zhang N, Xu L, Zhang X, Zhang J, Sung JJ, Yu J. Ras association domain family member 10 suppresses gastric cancer growth by cooperating with GSTP1 to regulate JNK/c-Jun/AP-1 pathway. Oncogene 2015Google Scholar
- 31.Konturek PC, Konturek SJ, Brzozowski T. Gastric cancer and Helicobacter pylori infection. J Physiol Pharmacol. 2006;57 Suppl 3:51–65.Google Scholar
- 35.Wang F, Feng Y, Li P, Wang K, Feng L, Liu YF, Huang H, Guo YB, Mao QS, Xue WJ. RASSF10 is an epigenetically inactivated tumor suppressor and independent prognostic factor in hepatocellular carcinoma. Oncotarget 2015Google Scholar