Objective: Cancer is becoming the number one killer in China now. The low specificity and sensitivity of the current cancer markers makes it not an ideal biomarker for the detection of cancer. In this study, we have summarized three-year multi-center study of surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOF-MS) to differentiate cancer from non-cancer controls in China. Method: Serum samples were collected from ten types of carcinoma confirmed by pathology under 4oC and distributed into five 100-uL aliquots with 9 M Urea and /or stored frozen at - 80 oC immediately. Samples were thawed, added to ProteinChip® and analyzed by SELDI-TOF-MS. Before each round of the analysis, we routinely performed standard quality control of serum samples to normalize different assays and different instruments so that all proteomic spectra are remained relatively constant like EKG through standardization of SELDI-TOF-MS in all centers (Kang XX, Xu Y, Wu XY et al, Clin. Chem. published November 18, 2004 online). Result: The analysis using differentially expressed peptides and proteins resulted in a predictive equation which correctly distinguished cancer from all non-cancer patients in blinded tests with a sensitivity and a specificity as following: hepatocellular carcinoma (91% and 89%), lung carcinoma (82% and 95%), gastric carcinoma (91% and 94%), esophageal carcinoma (84% and 91%), prostate carcinoma (83% and 97%), breast carcinoma (93% and 91%), colon carcinoma (83% and 92%), pancreatic carcinoma (82% and 85%), ovarian carcinoma (99% and 99%) and nasopharyngeal carcinoma (92% and 97%). Conclusion: Based on the review for the three-year (2002-2004 year) studies in China, we found that the specific cancer type using hydrophobic, anionic, cationic, and metal binding ProteinChip has little difference to affect specificity (10-15% variation) for the cancer detection. In addition, anionic ProteinChip has got the best result for the early detection of all types of cancers. Therefore, using one type of anionic ProteinChip as the standard protocol to set up Chinese cancer fingerprinting graphic bank is necessary. Due to existing of regional and race differentiation in China, we are planning to set up national Chinese cancer fingerprinting graphic bank for future diagnosis and prognosis of cancer. The proteomic fingerprintings are also currently under evaluation to determine whether it is suitable for early diagnosis of cancer and/or prognostic follow-up for the cancer. We found that none of the serum proteomic fingerprinting graphics is similar for all types of carcinoma tested. Therefore, serum proteomic fingerprinting graphics could be used as reference range for different types of carcinoma like EKG for cardiovascular disease. Protein identification of these potential markers is in progress.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]