Clinicopathologic correlation of up-regulated genes identified using cDNA microarray and real-time reverse transcription-PCR in human colorectal cancer.
OBJECTIVE
We hypothesize that changes in the transcription of up-regulated genes are biologically meaningful and may be linked to variations in tumor behavior and clinical features. This study aimed to find individual up-regulated genes responsible for clinicopathologic variations in human colorectal cancer.


METHODS
Genes up-regulated concurrently in four microarray experiments were taken as candidate genes; 20 candidate genes were verified using real-time reverse transcription-PCR in these four experiments, along with 27 new samples. The presence or absence of up-regulation of these genes was correlated with 10 clinicopathologic variables from 31 patients. The mRNA transcript levels of these 20 candidate genes in the 31 paired samples were also correlated with each other to disclose any expression relationship.


RESULTS
Forty percent (8/20) of the candidate genes were verified by real-time reverse transcription-PCR to have a tumor/normal expression ratio > 2. Up-regulation of THY1 and PHLAD1 was associated with the presence of anemia in colon cancer patients (P = 0.036 and 0.009, respectively). Up-regulation of HNRPA1 was more significant in cancer growing in the right-sided colon than the left side (P = 0.027). Up-regulated GPX2 was related to a higher degree of tumor differentiation (P = 0.019). c-MYC was significantly over-expressed in specimens from male compared with female colon cancer patients (P = 0.012). GRO1 was significantly up-regulated in patients younger than 65 years old (P = 0.010) and was found to be frequently over-expressed when cancers were less invasive. In addition, we found that normalized transcript levels of HNRPA1 were tightly associated with that of c-MYC (r = 0.948).


CONCLUSIONS
Validation of microarray data using another independent laboratory approach is mandatory and statistical correlation between gene expression status and the patient's clinical features may reveal individual genes relevant to tumor behavior and clinicopathologic variations in human colorectal cancer.
Chiu
Sou-Tyau
ST
Department of Surgery, Feng-Yuan Hospital, Feng-Yuan City, Tiachung County, Taipei, Taiwan.
Hsieh
Fon-Jou
FJ
Chen
Shi-Wen
SW
Chen
Chun-Lieh
CL
Shu
Hwei-Fan
HF
Li
Hung
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D018076:DNA, Complementary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D005979:Glutathione Peroxidase / Q000235:genetics; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics; D018800:Thy-1 Antigens / Q000235:genetics; D013951:Thymus Hormones / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D036341:Intercellular Signaling Peptides and Proteins; C491923:PHLDA1 protein, human; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D018800:Thy-1 Antigens; D013951:Thymus Hormones; D014157:Transcription Factors; C000619656:hnRNPA1 protein, human; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase