Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring.
BACKGROUND
Up to now, there is still no ideal tumor marker in early diagnosis and effective monitoring, especially for surgical resection of colorectal cancer (CRC). The aim of the present study was to evaluate the application of urinary normal and modified nucleosides in diagnosis and surgery monitoring of CRC.


METHODS
Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were enrolled. Spontaneous urine samples were collected 1 day before surgery and on day 8 postoperatively, and 14 urinary nucleosides were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Another 62 healthy people were also studied as control. The clinical routine tumor markers, serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, and alpha-fetoprotein (AFP) of CRC patients, were correspondingly evaluated by electrochemiluminescent immunoassay.


RESULTS
The levels of 11 out of 14 of the determined urinary nucleosides in the CRC group were much higher than those of normal controls. Through the principal component analysis of these 14 nucleosides, 76.9% of CRC patients were correctly classified. The sensitivity of this analysis was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%; P < 0.01). Receiver operating characteristic (ROC) curve analysis of 1-methylguanosine (m1G) and pseudouridine (Pseu) showed good sensitivity-specificity profiles of the diagnosis of CRC. The elevated levels of the nine nucleosides significantly decreased after curative resection of 40 CRC cases. The data also showed that the preoperative levels of some nucleosides were positively related with tumor size and Dukes staging of CRC.


CONCLUSIONS
The evaluation of normal and modified urinary nucleosides might become novel tumor markers, which will be facilitated in the clinical setting and helpful in the diagnosis, management and follow up of CRC. Pseu and m1G may be more promising for clinical use and be worthy of further studies in the near future.
Feng
Bo
B
Department of General Surgery, Ruijin Hospital, Shanghai Minimally Invasive Surgery Center, Shanghai Institute of Digestive Surgery, Shanghai Second Medical University, Shanghai, China.
Zheng
Min-Hua
MH
Zheng
Yu-Fang
YF
Lu
Ai-Guo
AG
Li
Jian-Wen
JW
Wang
Ming-Liang
ML
Ma
Jun-Jun
JJ
Xu
Guo-Wang
GW
Liu
Bing-Ya
BY
Zhu
Zheng-Gang
ZG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine*; D018394:CA-125 Antigen / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000652:urine*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D009705:Nucleosides; D000509:alpha-Fetoproteins