REG Iα gene expression is linked with the poor prognosis of lung adenocarcinoma and squamous cell carcinoma patients via discrete mechanisms

The aim of the present study was to evaluate the effects of the REG I and REG I genes on lung cancer cell lines, and thereafter, the expression of REG family genes (REG I, REG I, REG III, HIP/PAP and REG IV) in lung cancer in relation to patient prognosis was evaluated. Lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) cell lines expressing REG I or REG I (HLC-1 REG I/I and EBC-1 REG I/I) were established, and cell number, cell invasive activity, and anchorage-independent cell growth were compared with these variables in the control cells. The expression levels of REG family genes were evaluated by real-time RT-PCR in surgically resected lung cancers, and disease-specific survival (DSS) curves were generated. The HLC-1 REG I/I cell line showed significant increases in cell number and anchorage-independent cell growth compared with the control cells. EBC-1 REG I/I cells showed significant increases in cell invasive activity and anchorage-independent cell growth as compared with the control cells. Except for the REG I gene, expression of other REG family genes was observed in the surgically resected samples; however, DSS was significantly worse only in stage I patients who were positive for REG I expression than in patients who were negative for REG I expression. The effects of REG I on AD and SCC cells were different in the in vitro study, and a correlation between REG I expression and patient prognosis was noted in the in vivo study. Therefore, overexpression of REG I is a risk factor for poor prognosis caused by discrete mechanisms in AD and SCC patients.