Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients
- 729 Downloads
Due to ethnic, genetic and environmental factors, the clinical and molecular characteristics of Turkish colorectal cancer (CRC) patients are different from those of Western populations. The aim of this study was to clarify the relevant alterations of gene expression associated with colorectal carcinogenesis in early-onset patients and to identify specific biomarkers that could provide novel therapeutic molecular targets in this population.
The expression profiles of 114 different genes were evaluated using mRNA PCR arrays in 39 tumors and 20 surgical margin tissue samples from 39 sporadic CRC patients diagnosed at less than 50 years of age.
The expression levels of IMPDH2, CK20, MAP3K8 and EIF5A were strongly up-regulated in CRC tissues compared with normal colorectal tissues (p < 0.05). The highly significant expression ratios of CK20, MAP3K8 and EIF5A observed in the colorectal tumors of patients predicted recurrence (p < 0.05). The expression of IMPDH2, CK20, MAP3K8 and EIF5A was significantly higher in the tumors of patients with short median survival (log-rank p value < 0.05). Progression-free survival was also significantly increased in patients with low expression of the EIF5A gene compared with those who exhibited high expression of this gene (log-rank p value < 0.05).
We demonstrated that high CK20, MAP3K8 and EIF5A expression levels were significant prognostic factors for poor overall survival in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for CRC treatment, as well as new directions for the development of anticancer drugs.
KeywordsColorectal cancer CK20 MAP3K8 EIF5A Poor prognosis Turkish population
This work was supported by the Science Foundation of Uludag University (Project number; T (U)-2009/6).
Conflict of interest
- Ajao OG, Adenuga MO, Lapido JK (1988) Colorectal carcinoma in patients under the age of 30 years; a review of 11 cases. JR Coll Surg Edinb 33(5):277–279Google Scholar
- Brouwer C, Vermunt-de Koning DG, Trueworthy RC, Ter Riet PG, Duley JA, Trijbels FJ, Hoogerbrugge PM, Bokkerink JP, van Wering ER, De Abreu RA (2006) Monitoring of inosine monophosphate dehydrogenase activity in mononuclear cells of children with acute lymphoblastic leukemia: enzymological and clinical aspects. Pediatr Blood Cancer 46(4):434–438PubMedCrossRefGoogle Scholar
- Chen W, Luo JH, Hua WF, Zhou FJ, Lin MC, Kung HF, Zeng YX, Guan XY, Xie D (2009) Overexpression of EIF-5A2 is an independent predictor of outcome in patients of urothelial carcinoma of the bladder treated with radical cystectomy. Cancer Epidemiol Biomarkers Prev 18(2):400–408PubMedCrossRefGoogle Scholar
- Chiang JM, Chen MC, Changchien CR, Chen JS, Tang R, Wang JY, Yeh CY, Fan CW, Tsai WS (2003) Favorable influence of age on tumor characteristics of sporadic colorectal adenocarcinoma: patients 30 years of age younger may be a distinct patient group. Dis Colon Rectum 46(7):904–910PubMedCrossRefGoogle Scholar
- Forozan F, Mahlamäki EH, Monni O, Chen Y, Veldman R, Jiang Y, Gooden GC, Ethier SP, Kallioniemi A, Kallioniemi OP (2000) Comparative genomic hybridization analysis of 38 breast cancer cell lines: a basis for interpreting complementary DNA microarray data. Cancer Res 60(16):4519–4525PubMedGoogle Scholar
- Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Podar K, Le Gouill S, Shiraishi N, Yasui H, Roccaro AM, Tai YZ, Chauhan D, Fram R, Tamura K, Jain J, Anderson KC (2005) Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway. Oncogene 24(38):5888–5896PubMedCrossRefGoogle Scholar
- Pack SD, Karkera JD, Zhuang Z, Pak ED, Balan KV, Hwu P, Park WS, Pham T, Ault DO, Glaser M, Liotta L, Detera-Wadleigh SD, Wadleigh RG (1999) Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations. Genes Chromosomes Cancer 25(2):160–168PubMedCrossRefGoogle Scholar
- Turkish Ministry of Health, (1999) http://www.saglik.gov.tr
- Yang GF, Xie D, Liu JH, Luo JH, Li LJ, Hua WF, Wu HM, Kung HF, Zeng YX, Guan XY (2009) Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma. Gynecol Oncol 112(2):314–318PubMedCrossRefGoogle Scholar