Molecular Marker Identification for Relapse Prediction in 5-FU-Based Adjuvant Chemotherapy in Gastric and Colorectal Cancers

To confirm the clinical significance of NF-kB and JNK protein expression from experimentally identified candidates for predicting prognosis for patients with 5-FU treatment, we evaluated the protein expression of surgically removed specimens. A total of 79 specimens were obtained from 30 gastric and 49 colorectal cancer patients who underwent R0 resection followed by postoperative 5-FU based adjuvant chemotherapy. Immunohistochemical examinations of NF-kB and JNK on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-kB(+) and JNK(2) subgroups in both gastric (NF-kB(+), p = 0.0002, HR11.7. 95%CI3 3.2–43.4; JNK(2), p = 0.0302, HR4.4, 95%CI 1.2–16.6) and colon (NF-kB(+), p = 0.0038, HR36.9, 95%CI 3.2–426.0; JNK(2), p = 0.0098, HR3.2, 95%CI 1.3–7.7) cancers. These protein expression patterns also show strong discriminately power in gastric cancer patients for overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline expression of these proteins using gastric cancer cell lines demonstrated the reciprocal patterns between NF-kB and JNK, while 5-FU exposure of these cell lines only induced NF-kB, suggesting that NF-kB plays a dominant role in the response to 5-FU. Subsequent siRNA experiments confirmed tha