Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer

Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve the anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. Our purpose of this study was to identify a set of discriminating genes that can be used for characterization and prediction of response to CRT in rectal cancer.

Seventeen rectal cancer patients who underwent preoperative CRT (40 Gy radiotherapy combined with S-1) were studied. Biopsy specimens were obtained from rectal cancer patients before preoperative CRT and were analyzed by focused DNA microarray (132 genes) and immunohistochemistry. Response to CRT was determined by histopathologic examination of surgically resected specimens and patients were classified as responders (grade 2 or 3) or non-responders (grade 0 or 1).

Of the 17 samples, 10 were classified as responders and 7 as non-responders. Seventeen genes were differentially expressed at significant levels (p<0.05) between responders and non-responders. All genes showed higher expression in responders as compared with non-responders. The list of discriminating genes included matrix metalloproteinase- (MMP), apoptosis- (nuclear factor kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), transforming growth factor beta 1 (TGFB1)), DNA repair- (topoisomerase 1 (TOP1)), and cell proliferation (integrin, beta 1 (ITGB1))-related genes. In the immunohistochemistry of MMP7, 4 responders were judged as showing overexpression of MMP7. On the other hand, none of the non-responders were judged as showing overexpression of MMP7.

Gene expression patterns of diagnostic biopsies can predict pathological response to preoperative CRT with S-1 in rectal cancer.