Differential expression of human telomerase reverse transcriptase β-site remaining alternative splicing variants (hTERT β+ ASV) in gastric carcinogenesis

Abstract

e15641 Background: To investigate the changes of hTERT alternative splicing variants pattern in gastric cancer, precancerous lesions and normal gastric mucosa tissue. Methods: Three alternative splicing sites (α, β, γ) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in gastric cancer, precancerous lesions and normal gastric mucosa were detected by Semi-nested RT-PCR. The expression of β-site remaining ASV (β+ASV) in specimens of gastric cancer and specimens of precancerous lesions was detected by SYBER Green real-time PCR. Telomerase enzyme activity was evaluated associated with the different hTERT ASVs. Results: The positive rate of active full-length (α+β+γ+ ) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P<0.05). The positive rates of other ASVs were not different among the 3 groups(P>0.05). The positive rates of β+ ASVs (including α+β+γ+ASV, α-deletion ASV, γ-deletion ASV, αγ-deletion ASV) were 11.1% in normal mucosa,40.0% in precancerous lesions and 94.7% in gastric cancer (P<0.05). SYBR Green real-time RT-PCR showed that the expression level of β+ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Further, increased telomerase enzyme activity was only associated with expression of the full-length hTERT isoform. Conclusions: hTERT alternative splicing pattern is different during gastric carcinogenesis. β+ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions. The gene expression patterns of hTERT alternative splicing variants may provide some useful information for diagnosis of gastric cancer and precancerous lesions. No significant financial relationships to disclose.