Putative chemosensitivity predictive genes in colorectal cancer cell lines for anticancer agents.
In order to identify genes which could predict chemosensitivity in colorectal cancer, gene expression and chemosensitivity were examined in colorectal cancer cell lines. Gene expression profiling of 5 colorectal cancer and 3 normal cell lines was performed using a 22K spotted oligonucleotide microarray. The IC50s of 17 anticancer drugs were determined using the MTT assay for chemosensitivity. The SOURCE database, KEGG Pathway database, and Molecular Diagnosis Score (MDS) were used for data analysis. Two representative colorectal cancer cell lines were identified which were resistant or sensitive to drugs commonly used for colon cancer treatment (5-FU, irinotecan and topotecan). Six hundred and eighty-three genes that were up- or down-regulated by >4-fold between the two cell lines were selected. Pathway analysis was performed with 147 of the 683 genes using the KEGG Pathway database. This analysis revealed 27 genes in the apoptosis, MAPK signaling, and focal adhesion pathways, which could explain the mechanism of chemosensitivity in colorectal cancer cell lines. In addition, the chemosensitivity of other colorectal cancer and normal cell lines was predictable with the selected 27 genes. These genes may act as putative predictive markers for chemosensitivity in chemo-naive colorectal cancer patients following functional analysis and clinical validation.
Jung
Jae-Joon
JJ
Cancer Metastasis Research Center, Yonsei University College of Medicine, Shinchon-Dong, Seoul, Korea.
Jeung
Hei-Cheul
HC
Lee
Jung Ok
JO
Kim
Tae Soo
TS
Chung
Hyun Cheol
HC
Rha
Sun Young
SY
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm