Expressions Of TRF2, TIN2, TERT, And KU70 Protein And Their Relationships With Telomere Length During Multistage Carcinogenesis Of Gastric Cancer

Objective: To explore the relationship between expressions of telomeric protein TRF2, TIN2, TERT as well as KU70 and telomere length during human multistage carcinogenesis of gastric cancer.Methods: 10 normal gastric mucosa, 15 precancerous lesions, 20 gastric cancer and 5 lymph nodes with gastric cancer metastasis were chosen by micro-dissection. Expression of TRF2 and TIN2 protein was measured by Western blot, TERT and KU70 by immunohistochemistry and telomere length by Southern blot analysis.Results: The TRF2, and TIN2 protein levels were significantly higher in precancerous lesions, GC and GCLM than that in normal gastric mucosa tissues (P<0.01). These protein levels in GC and GCLM were significantly higher than that in precancerous lesions (P<0.01). The expression of TERT and Ku70 protein was significantly higher in precancerous lesions and GC than that in normal gastric mucosa tissues (P<0.01). These protein levels in GC were significantly higher than that in precancerous lesions (P<0.01). Ku70 was found in precancerous lesion with cytoplasmic expression and in GC with nuclear expression. The telomere length was significantly shorter in precancerous lesions, GC and GCLM than that in normal gastric mucosa tissues (P<0.05). The telomere lengths in GC and GCLM were significantly shorter than in precancerous lesions (P<0.05). The telomere lengths were inversely correlated with the protein level of TRF2, TIN2, TERT and Ku70. In GC, only tumor differentiation emerged as significant parameters with TRF2, TIN2 protein level (P<0.05). The normal gastric mucosa showed telomere lengths negatively correlated with the patient ages (R2=0.851, P<0.01).Conclusion: Expressions of telomere protein TRF2, TIN2, TERT and Ku70 in the normal gastric mucosa, precancerous lesions, gastric cancer, metastatic carcinoma increase gradually. Up-regulation of these proteins may be related to the carcinogenesis and progression of gastric cancer. TRF2 and TIN2 protein expressions are associated with the degree of tumor differentiation. The mean telomere lengths in the normal gastric mucosa, precancerous lesions, gastric cancer and metastatic carcinoma gradually shorten. Telomere length may be involved in the carcinogenesis and progression of gastric cancer. Telomere shortening is the early event of gastric cancer. Telomere length is negatively correlated to TRF2, TIN2, TERT, Ku70 protein levels. Telomere protein expression may be working together to reduce the telomere length, thus promoting the development of gastric cancer.