Differential expression of Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2) in human colorectal cancer progression using human cancer cDNA microarrays.
In this study, we applied commercially available cDNA microarray systems (1068 genes) to investigate the genetic changes in six colorectal cancers (CRC). Thirty-two genes fell into the group of commonly upregulated genes. In addition, we immunohistochemically investigated the expression of the four top ranked upregulated genes, Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2), in 44 CRC. JAK3 staining was located in the cancer cells. A comparison of JAK3 immunostaining and clinicopathological parameters showed a significant association of tumor differentiation, pT, and TMN stage. Staining of MMP13 and HSP60 was noted mainly in the cytoplasm of cancer cells. A significant association of these expressions was observed with tumor differentiation and pT. MDM2 staining was noted in the nucleus of cancer and non-cancer cells. No significant association of clinicopathological parameters with MDM2 expression was observed. In multivariate analysis, JAK3 immunoreactivity showed independent prognostically unfavorable predictors. These data suggest that JAK3, in particular, is a highly significant, prognostic immunohistochemical marker in CRC. This study proves that cDNA microarrays, plotted by a small number of genes from a few samples, are both practical and useful.
Mori
Daisuke
D
Department of Pathology and Biodefense, School of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan. mori-d@koseikan.jp
Nakafusa
Yuji
Y
Miyazaki
Kohji
K
Tokunaga
Osamu
O
D000236:Adenoma / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053616:Janus Kinase 3; D053509:Matrix Metalloproteinase 13; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018834:Chaperonin 60; C060293:HSPD1 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D018833:Chaperonins