title: Association between mRNA expression of chemotherapy-related genes and clinicopathological features in colorectal cancer: A large-scale population analysis.
abstract: To establish the individualized treatment of patients with colorectal cancer, factors associated with chemotherapeutic effects should be identified. However, to the best of our knowledge, few studies are available on this topic, although it is known that the prognosis of patients and sensitivity to chemotherapy depend on the location of the tumor and that the tumor location is important for individualized treatment. In this study, primary tumors obtained from 1,129 patients with colorectal cancer were used to measure the mRNA expression levels of the following genes associated with the effects of standard chemotherapy for colorectal cancer: 5-fluorouracil (5-FU)-related thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP); folate-related dihydrofolate reductase (DHFR), folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH); irinotecan-related topoisomerase I (TOP1); oxaliplatin-related excision repair cross-complementing 1 (ERCC1); biologic agent-related vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Large-scale population analysis was performed to determine the association of gene expression with the clinicopathological features, in particular, the location of the colorectal cancer. From the results of our analysis of the mRNA expression of these 10 genes, we noted the strongest correlation between DPYD and TYMP, followed by TYMS and DHFR. The location of the colorectal cancer was classified into 4 regions (the right‑ and left-sided colon, rectosigmoid and rectum) and was compared with gene expression. A significant difference in all genes, apart from VEGF, was noted. Of the remaining 9 genes, the highest expression of TYMS and DPYD was observed in the right‑sided colon; the highest expression of GGH and EGFR was noted in the left-sided colon; the highest expression of DHFR, FPGS, TOP1 and ERCC1 was noted in the rectosigmoid, whereas TYMP expression was approximately equivalent in the right-sided colon and rectum, and higher than that in other locations. The data generated from this study may prove to be useful for the development of individualized chemotherapeutic treatments for patients with colorectal cancer, and will mean that the tumor location is taken into account.
authors.affiliation: Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Uchikanda, Chiyoda-ku, Tokyo 101-0047, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimamoto
authors.affiliation: Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Kawauchi-Cho, Tokushima‑shi, Tokushima 771-0194, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Nukatsuka
authors.affiliation: Translational Research Laboratory, Taiho Pharmaceutical Co., Ltd., Uchikanda, Chiyoda-ku, Tokyo 101-0047, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Takechi
authors.affiliation: The Japan-Multinational Trial Organization, Naka-ku, Nagoya-shi, Aichi 460-0002, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004720:Endonucleases / Q000096:biosynthesis* / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010453:Peptide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000096:biosynthesis* / Q000235:genetics; D011623:gamma-Glutamyl Hydrolase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D000077146:Irinotecan; D013762:Tetrahydrofolate Dehydrogenase; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase; C512478:EGFR protein, human; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D011623:gamma-Glutamyl Hydrolase; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase; D005472:Fluorouracil; D002166:Camptothecin