Objective: To study the difference of proteomic spectra in serum between patients with colorectal cancer (CRC) and CRC with liver metastases (LMCRC), try to find out specifical biological markers for CRC and LMCRC, build a proteomic pattern and find a early diagnosis method for CRC and LMCRC.Methods:82 serum specimens were collected from June 2008 to Febuary 2009, including 30 healthy controls, 52 colorectal cancer and 24 colorectal cancer liver metastases. All CRC and liver metastasis were diagnosed by the pathologic and/or iconograpy. Using CM10 protein chip and surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) were used to detect the relative content of serum proteins, the protein would be transformed to spectrum by the PBSâ…¡protein chip reader. All the 3 groups patients were compared as follow:â‘ CRC group and the healthy control group.â‘¡LMCRC group and CRC group.â‘¢LMCRC group and the healthy control group. The different protein content and M/Z in each of the 3 groups were compared by using Biomarker Wizard software. The specifical Biological Markers were found and the diagnostic cast of CRC and LMCRC was constructed. The constructed pattern was then tested by an independent set of masked serum samples from 33 colorectal cancer patients and 34 healthy subjects, and the protein were determined by the SWISS-PROT protein database.Results: 1) Compared CRC group and healthy control group: The contents of 22 proteins in the two groups were different(P<0.05) from 2106.59Da to 47811.15Da,13 proteins express higher in CRC while 9 proteins express higher in healthy subjects. After setting up a diagnosis model at M/Z 3223.43,7971.57 and 11493.00. The accurate rate of the model training model was 85.37%, sensitivity was 80.76% and specificity was 93.33% and the accurate rate of the model learning set was 91.46%, sensitivity was 88.46% and specificity 96.66%. A sensitivity of 72.73% (24/33) and a specificity of 91.18% (31/34) for the blinded test were obtained by blind test with CRC patients and healthy people.2) Compared LMCRC group and CRC group: The contents of 34 proteins in the two groups were different(P<0.05) from 2106.59Da to 47811.15Da,16 proteins express higher in LMCRC while 18 proteins express higher in CRC. After setting up a diagnosis model at M/Z 3223.43,3511.88 and 8894.49. The accurate rate of the model training model was 82.69%, sensitivity was 79.17% and specificity was 85.71% and the accurate rate of the model learning set was 94.23%, sensitivity was 95.83% and specificity 92.86%. 3) Compared LMCRC group and the healthy control group: The contents of 40 proteins in the two groups were different(P<0.05) from 2106.59Da to 47811.15Da,24 proteins express higher in LMCRC while 16 proteins express higher in healthy subjects. After setting up a diagnosis model at M/Z 11492.90 and 4532.84. The accurate rate of the model training model was 94.44%, sensitivity was 95.83% and specificity was 93.33% and the accurate rate of the model learning set was 98.15%, sensitivity was 100% and specificity 96.67%.4) Cathepsin B and Proepiregulin were identified as tumor markers for liver metastases from colorectal cancer.Conclusions: There are some specific protein compared between colorectal cancer, liver metastases of colorectal cancer patients and healthy, which are expected to be an early diagnosis way for CRC and / or LMCRC patients by the establishment of diagnostic model. The selected tumor markers in this experiment may be important in diagnosis and prognosis for liver metastasis from colorectal cancer. SELDI-TOF-MS technology is expected to be early diagnosis of colorectal cancer and liver metastasis of fast, efficient and sensitive detection.
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