Expression profiling of fecal colonocytes for RNA-based screening of colorectal cancer.
The early detection of colorectal cancer originating from any part of the colorectum is desirable because this cancer can be cured surgically if diagnosed early. We searched for marker genes for a fecal RNA-based colorectal cancer screening method by comparison of genome-wide expression profiles among cancerous and non-cancerous tissues, and healthy volunteer- and cancer patient-derived colonocytes from the feces, and the peripheral blood. Of 14,564 genes, only 3 (PAP, REG1A, and DPEP1) were selectable as final candidates which were expressed frequently at any stage of this cancer and were suppressed in non-cancerous tissues and also in the peripheral blood and colonocytes of healthy volunteers. Next, we directly compared fecal RNA-expression profiles between colorectal cancer patients and healthy volunteers, and found that most of the genes (92%) expressed in the colonocytes of the cancer patients were not expressed in those of the healthy volunteers. Six genes (SEPP1, RPL27A, ATP1B1, EEF1A1, SFN, and RPS11) selected randomly from 85 cancer patient-derived colonocyte-specific genes were evaluated. In total, reverse transcription-polymerase chain reaction or focused microarray of all those 9 genes detected 18 (78%) of 23 curable colorectal cancers (Dukes stages A-C), 9 or 10 (64% or 71%) of 14 early cancers with no lymph node metastasis (Dukes stage A or B) and 4 (80%) of 5 right-sided cancers. Our extensive gene list provides other markers for fecal RNA-based colorectal cancer screening.
Yajima
Satoshi
S
Genetics Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
Ishii
Mie
M
Matsushita
Hisayuki
H
Aoyagi
Kazuhiko
K
Yoshimatsu
Kazuhiko
K
Kaneko
Hironori
H
Yamamoto
Nobuko
N
Teramoto
Tatsuo
T
Yoshida
Teruhiko
T
Matsumura
Yasuhiro
Y
Sasaki
Hiroki
H
D001483:Base Sequence; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism*; D005243:Feces / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction