Multiple molecular markers as predictors of colorectal cancer in patients with normal perioperative serum carcinoembryonic antigen levels.
OBJECTIVE
In this study, a high-sensitivity colorimetric membrane array method was used to detect circulating tumor cells (CTC) in the peripheral blood of colorectal cancer (CRC) patients with normal perioperative serum carcinoembryonic antigen (CEA) levels. This membrane array method was evaluated as a potential diagnostic and postoperative surveillance tool.


METHODS
Membrane arrays consisting of a panel of mRNA markers that include human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and CEA mRNA were used to detect CTCs in the peripheral blood of 157 postoperative CRC patients with normal perioperative serum CEA levels and in 80 healthy individuals. Digoxigenin-labeled cDNA were amplified by reverse transcription-PCR from the peripheral blood samples, which were then hybridized to the membrane array. The sensitivity, specificity, and accuracy of membrane arrays for the detection of CTCs were then calculated.


RESULTS
Using the four markers in combination, expression of any three markers or all the four markers in this panel was significantly correlated with the clinicopathologic characteristics, including depth of tumor invasion, lymph node metastasis, tumor-node-metastasis stage, and postoperative relapse (all P < 0.05). The interval between the detection of all four positive molecular markers and subsequent elevated CEA ranged from 3 to 8 months (median 6 months). The expression of all four mRNA markers was an independent predictor for postoperative relapse. CRC patients with all four mRNA markers expression showed a significantly poorer survival rate than those with less than four positive markers.


CONCLUSIONS
The constructed membrane array method was helpful in the early prediction of postoperative relapse in CRC patients with normal perioperative serum CEA levels.
Wang
Jaw-Yuan
JY
Department of Surgery, Kaohsiung Medical University Hospital, Taiwan.
Lin
Shiu-Ru
SR
Wu
Deng-Chyang
DC
Lu
Chien-Yu
CY
Yu
Fang-Jung
FJ
Hsieh
Jan-Sing
JS
Cheng
Tian-Lu
TL
Koay
Lok-Beng
LB
Uen
Yih-Huei
YH
D000368:Aged; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery*; D003124:Colorimetry / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002272:Carcinoembryonic Antigen; D015345:Oligonucleotide Probes; D012333:RNA, Messenger