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Elevated Expression of SCGB1D2 Predicts Unfavorable Prognosis in Patients with Pancreatic Ductal Adenocarcinoma

Keisuke Taniuchi, Mutsuo Furihata, Seiji Naganuma, Masashi Kimura, Ryohei Watanabe, Hiroshi Mizuta, Nobuto Okamoto, Takuhiro Kohsaki, Ken Dabanaka, Kazuhiro Hanazaki, Toshiji Saibara

Context SCGB1D2 is a member of the secretoglobin superfamily, but little is known about the functional and prognostic value of this protein in pancreatic cancer. In the current study, we investigated the expression pattern and underlying clinical significance of SCGB1D2 in pancreatic cancer. Methods Immunohistochemistry was performed to determine whether high SCGB1D2 expression in 102 resected pancreatic cancer tissues was correlated with poor patient prognosis. Immunocytochemistry was also performed to determine the intracellular distribution of SCGB1D2. To determine whether SCGB1D2 participated in the formation of cell protrusions and the accumulation of peripheral actin-filaments in pancreatic cancer cells, SCGB1D2 expression was transiently suppressed by small-interfering RNA knockdown. Results Kaplan-Meier analysis showed that pancreatic cancer patients with higher SCGB1D2 expression exhibited a remarkably shorter overall survival. Importantly, univariable and multivariable Cox regression analysis revealed that SCGB1D2 protein expression level was a significant and independent prognostic factor for overall survival in these patients. However, no correlation was found between SCGB1D2 expression and clinicopathological parameters. Membranous expression of SCGB1D2 in pancreatic cancer cells was found in 36.3% of pancreatic cancer patients, but was not an independent risk factor for progressive disease and death. Membranous SCGB1D2 expression was found to be associated with histology grade but no other clinicopathological parameters. Immunocytochemistry demonstrated that SCGB1D2 was localized to the cell protrusions of migrating pancreatic cancer cells. Knockdown of SCGB1D2 decreased the formation of these protrusions, but the effect could be abrogated by co-transfection with an SCGB1D2-rescue construct. Conclusions SCGB1D2 is an unfavorable biomarker of prognosis in pancreatic cancer and plays a role in the formation of cell protrusions important for cancer cell migration.