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

作者: Kazushige Ishida , Satoshi S. Nishizuka , Takehiro Chiba , Miyuki Ikeda , Kohei Kume

DOI: 10.1371/JOURNAL.PONE.0043236

关键词:

摘要: To confirm the clinical significance of NF-κB and JNK protein expression from experimentally identified candidates for predicting prognosis patients with 5-FU treatment, we evaluated surgically removed specimens. A total 79 specimens were obtained 30 gastric 49 colorectal cancer who underwent R0 resection followed by postoperative based adjuvant chemotherapy. Immunohistochemical examinations on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-κB(+) JNK(−) subgroups (NF-κB(+), p = 0.0002, HR11.7. 95%CI3 3.2–43.4; JNK(−), p = 0.0302, HR4.4, 95%CI 1.2–16.6) colon p = 0.0038, HR36.9, 3.2–426.0; p = 0.0098, HR3.2, 1.3–7.7) cancers. These patterns also show strong discriminately power overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline these proteins using cell lines demonstrated reciprocal between JNK, while exposure only induced NF-κB, plays dominant role response to 5-FU. Subsequent siRNA experiments confirmed gene knockdown increased 5-FU-specific sensitivity, whereas did not affect chemosensitivity. results suggest may aid decisions involved chemotherapy gastrointestinal tract

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