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Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis

Nogimori, K;Hori, T;Kawaguchi, K;Fukui, T;Mii, S;Nakada, H;Matsumoto, Y;Yamauchi, Y;Takahashi, M;Furukawa, K;Tetsuya, O;Yokoi, K;Hasegawa, Y;Furukawa, K;

ppGalNAc-T13 is upregulated along with reduced expression of GM1 in high metastatic sublines of the murine Lewis lung cancer cell line, but little is known about the implication of ppGalNAc-T13 expression in human cancers. Since lung cancer cell lines showed high expression levels of ppGalNAc-T13, we analyzed ppGalNAc-T13 expression in surgical lung cancer specimens to examine whether ppGalNAc-T13 can be used as a prognostic marker or a therapeutic target. We analyzed mRNA expression levels of GALNT13 and its variant exon usages in surgical specimens by real-time RT-PCR, and the results were evaluated by correlating with clinical data. Ninety-one surgical specimens were analyzed. Consequently, recurrence-free survival was significantly shorter (P=0.045) in high expression group of GALNT13 mRNA. In the analysis of tumor specific exon usage in GALNT13 RNA sequence, one variant exon was significantly associated with worse prognosis. By contrast, in another variant exon, positive variant expression group showed better prognosis than negative group. We also tried to detect GALNT13 mRNA in 63 serum samples from patients with lung cancers to examine whether GALNT13 mRNA can be measured in body fluids, detecting significant levels in 4 samples. Finally, expression of GM1, ppGalNAc-T13 and trimeric Tn antigen was examined by immunohistochemistry in order to evaluate them as a prognostic factor. It was demonstrated that ppGalNAc-T13 and trimeric Tn antigen had a relationship with worse prognosis in 35 investigated lung cancer patients. In conclusion, our results suggest that ppGalNAc-T13 might be a useful prognostic factor of lung cancers.