Screening And Identification Of The Molecular Markers Of Colorectal Cancer With Liver Metastasis

【Background and Purpose】Colorectal cancer is one of the clinical common malignant tumors. Nearly half of the patients who have radical resection will relapse and metastasis, and recurrence and metastasis are the most important causes of poor prognosis and death. The liver is the most common distant metastasis organ of colorectal cancer patients. DNA copy number alterations play an important role in the initiation and progression of colorectal adenocarcinoma. In the present study, we used oligonucleotide array CGH to identify genetic alterations of colorectal cancer with liver metastasis.[Patients and Methods] The tissue samples were obtained from 16 colorectal cancer tissues. Genomic DNA was isolated, and array CGH was performed with the Agilent Human Genome CGH 8*60K array. Tissue microarray was constructed, containing 120 colorectal cancer tissues. The expression of cortactin. HSP70. Ki67. Mem7. p53.β-catenin. PTP-1B and DNA1B6 proteins were detected by using immunohistochemical method, and the relationships between the proteins expression and liver metastasis of colorectal cancer were analyzed.[Results] Array CGH showed that the most common genetic changes in colorectal cancer were gains of 7p,8q,13q, 19p,20q and losses of 4p.4q,8p,17p,18q,21q. High level amplifications at 13ql2.2-ql2.3.13q14.11 and 13q31.3 and homozygous deletions at 3q26.1,11q11,18q21.2,22q13.2 were also detected. By comparing the frequency of genomic changes in metastasis and non-metastasis patients.7p,8q and 18q showed most different frequency.. IHC analysis showed that Ki67, MCM7 and DNAJB6 expressed in 46.3%,74.1%and 66.7%of tumors, respectively. The positive expression of Ki67. MCM 7 and DNAJB6 was associated with liver metastases (Ki67:x2=7.424, P=0.006, MCM7: X2=24.371, P=0.001, DNAJB6:%2=4.673, P=0.031).[Conclusions] There existed lots of chromosomal loci with frequent alterations of DNA copy number in colorectal cancer with liver metastasis. Ki67. MCM7 and DNAJB6 might be useful biomarkers in more advanced stage of colorectal cancer.