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Aberrant methylation of suppressor of cytokine signaling-1 gene in human gastric carcinomas

Xiaochun Peng, Chengqiang Wang

Suppressor of cytokine signaling (SOCS)-1 inhibits signaling of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway by several cytokines and has tumor suppressor activity. Methylation of the SOCS-1 CpG island has been shown to inactivate the SOCS-1 gene in certain human cancers. In our study, we investigated methylation status of the SOCS-1 gene by methylation-specific PCR in 45 gastric carcinoma (GC) tissues, 18 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals. In addition, SOCS-1 mRNA levels were examined in 30 GCs by quantitative RT-PCR. Hypermethylation of the SOCS-1 gene was detected in 21 (46.7%) of 45 GC tissues and in 2 (11.1%) of 18 corresponding nonneoplastic mucosae; the incidence was significantly different (p = 0.0081). None of the 10 normal gastric tissues from healthy individuals showed hypermethylation. Methylation of the SOCS-1 gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS-1 in GC tissues (p = 0.0032, 0.0040 and 0.0026, respectively). Reduced expression of SOCS-1 in GC tissues was associated with lymph node metastasis and advanced tumor stage (p = 0.0143 and 0.0025, respectively). Our results suggest that transcriptional inactivation of the SOCS-1 gene by hypermethylation may be involved in development, progression and metastasis of GC.