Discovery of new markers of cancer through serial analysis of gene expression: Prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma

Serial analysis of gene expression (SAGE) can be used to quantify gene expr ession in human tissues. Comparison of gene expression levels in neoplastic tissues with those seen in nonneoplastic tissues can, in turn, identify no vel tumor markers. Such markers are urgently needed for highly lethal cance rs like pancreatic adenocarcinoma, which typically presents at an incurable , advanced stage. The results of SAGE analyses of a large number of neoplas tic and nonneoplastic tissues are now available online, facilitating the ra pid identification of novel tumor markers. We searched an online SAGE datab ase to identify genes preferentially expressed in pancreatic cancers as com pared with normal tissues. SAGE libraries derived from pancreatic adenocarc inomas were compared with SAGE libraries derived from nonneoplastic tissues , Three promising tags mere identified, Two of these tags corresponded to g enes (lipocalin and trefoil factor 2) previously shown to be overexpressed in pancreatic carcinoma, whereas the third tag corresponded to prostate ste m cell antigen (PSCA), a recently discovered gene thought to be largely res tricted to prostatic basal cells and prostatic adenocarcinomas, PSCA was ex pressed in four of the six pancreatic cancer SAGE libraries, but not in the libraries derived from normal pancreatic duetal cells, We confirmed the ov erexpression of the PSCA mRNA transcript in 14 of 19 pancreatic cancer cell Lines by reverse transcription-PCR, and using immunohistochemistry, we dem onstrated PSCA protein overexpression in 36 of 60 (60%) primary pancreatic adenocarcinomas. In 59 of 60 cases, the adjacent nonneoplastic pancreas did not label for PSCA, PSCA is a novel tumor marker for pancreatic carcinoma that has potential diagnostic and therapeutic implications, These results e stablish the validity of analyses of SAGE databases to identify novel tumor markers.