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Background Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. We developed a novel technique to identify cancer-related genes of HCC as follows: triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism arrays, and methylation arrays. Materials and methods Triple-combination array analysis was performed on one HCC sample from a 68-y-old female patient, and one candidate cancer-related gene was selected. Subsequently, we analyzed the identified gene by quantitative real-time reverse-transcriptase polymerase chain reaction (PCR) and methylation-specific PCR in nine HCC cell lines and in samples from 48 HCC patients. Additionally, we evaluated gene expression by immunohistochemistry and Western blotting. Results Using this method, protein tyrosine kinase 7 ( PTK7 ) was detected as a candidate cancer-related gene. PTK7 was revealed to be hypermethylated (methylation value 0.826, range 0–1.0) in cancer tissue, compared with that of adjacent noncancerous tissues (0.047) by methylation array. Of the 48 clinical samples, 30 HCC samples (62.5%) showed PTK7 promoter hypermethylation. Downregulation of PTK7 (expressions in tumor tissues decreased by ≥50% compared with the noncancerous tissues) was significantly associated with age >60 y ( P = 0.030) and elevation in serum protein induced by vitamin K absence or antagonists-II ( P = 0.033). Moreover, patients with downregulation were significantly inferior in overall survival ( P Conclusions Our data imply that PTK7 acts as a cancer-related gene and may be a potent prognostic marker for HCC. Triple-combination array analysis was once again found to be useful in identifying cancer-related genes.

302 Background: The aim of this study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) with S-1 (oral fluoropyrimidine) followed by surgery for the treatment of borderline resectable pancreatic cancer that involved the major visceral artery or the portal venous system. Methods: Twenty-eight patients with pancreatic cancers that abutted the SMA in 10, the CHA in 7, the both SMA and CHA in 1, and occluded the SMV/PV in 10 were treated with NACRT at a single institution. Radiation therapy was delivered at a total dose of 50.4 Gy in 28 fractions. S-1 was administered orally at a dose of 80 mg/m(2)/day for 14 consecutive days followed by a 7-day rest period during radiation therapy. After radiotherapy and 2 courses of S-1, restaging was done to evaluate secondary resectability. Results: Of the all patients, 25 underwent a full course of NACRT, and NACRT terminated in 3 patients because of grade 3 leukopenia in 2 and tumor bleeding in 1. Partial response was achieved in 3 patients and stable disease in 22. Twenty-four patients (86%) underwent surgical resection, and all had margin-negative (R0) resections. Only two patients (8%) had major morbidity as Clavien-Dindo’s classification III or more, and there was no operative or in-hospital mortality. Pathological examination revealed that more than 50% of tumor cells had disappeared in 14 cases and all cases achieved Evans’ score IIa and more. Conclusions: Neoadjuvant chemoradiation with S-1 was feasible and promising therapy for borderline resectable pancreatic cancer that involves the major artery or the portal venous system.

More information is needed about genetic factors that initiate development of pancreatic intraepithelial neoplasms-the most common precursors of pancreatic ductal adenocarcinoma. We show that more than 99% of the earliest-stage, lowest-grade, pancreatic intraepithelial neoplasm-1 lesions contain mutations in KRAS, p16/CDKN2A, GNAS, or BRAF. These findings could improve our understanding of the development and progression of these premalignant lesions.