[Application of SELDI-TOF-MS in detection of liver metastasis from colorectal cancer].

OBJECTIVE: To establish a serum protein fingerprint model for prediction of liver metastasis from colorectal cancer by SELDI-TOF-MS analysis, and to determine the differentiatial proteins associated with the metastatic liver cancers. METHODS: Data were collected from the Department of General Surgery in Zhongshan Hospital. A group of patients with colorectal cancer (CRC) without liver metastasis (n = 36) and another group with liver metastasis (n = 36) were included in this study. Serum samples were collected from peripheral venous blood before operation. Special serum protein or peptide fingerprint was determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The obtained data were analyzed by Biomarker Wizard software to screen the serum protein markers discriminating colorectal cancer patients with and without liver metastasis. A serum protein fingerprint model was established. This model was blindly verified in of CRC patients with and 44 cases without liver metastasis. RESULTS: Comparing the characteristic proteins in those two groups of patients, 10 specific protein peaks were identified with statistical significance (P < 0.05). According to m/z growing from small to large, they were: 2398, 2814, 4084, 4289, 4465, 6422, 6619, 11 482, 11 649 and 13 714. The predictive model had a sensitivity of 91.7% and a specificity of 97.2%. The validation showed a sensitivity of 75.0% and a specificity of 81.8%. CONCLUSION: A predictive model based on differentiatial serum protein fingerprint with high sensitivity and specificity has been successfully established. It should be a very useful tool in detection and diagnosis of liver metastasis in colorectal cancer patients.

[Establish predictive model of colorectal cancer by using surface enhanced laser desorption/ionization-time of flight-mass spectrometry].

OBJECTIVE: To establish serum proteome fingerprinting predictive models and search for proteins associated with colorectal cancer. METHODS: Thirty-six randomly selected colorectal cancer patients and 36 cases with hernia or gall bladder diseases scheduled for elective operation were enrolled as cancer group and control group respectively. Peripheral venous blood samples were collected before the operations. Special serum protein or peptide fingerprint was investigated by using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after blood sample had been treated with weak cation exchange protein chip (CM10) for each case. The obtained data were analyzed by Biomarker Wizard software to screen serum proteome tumor markers and set up diagnosis predictive model for colorectal cancer. Blind validation of the model with 44 healthy controls and 88 colorectal cancer patients were carried out by using Biomarker Patterns Software. RESULTS: In comparing colorectal cancer group with control group, 5 specific protein peaks (P < 0.05) were found. The predictive model had a sensitivity of 100% and a specificity of 97.2%. A sensitivity of 71.6% and a specificity of 72.7% was got with the blind validation. The specific protein peaks with a mass-to-charge ratio (m/z) of 8908 and 13,707 showed in all the results and it showed their strong relationship with colorectal cancer. CONCLUSIONS: The predictive models built by the differences of serum proteome fingerprint could be a very useful diagnostic tool in colorectal cancer. Proteins with m/z of 8908 and 13,707 would possibly be the tumor markers of colorectal cancer.

[Evaluation of cyclooxygenase-2 in the prediction of liver metastasis of colorectal carcinoma].

OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in colorectal carcinoma and its correlation with liver metastasis of colorectal carcinoma. METHODS: The expression of COX-2 was detected using immunohistochemical methods in 30 colorectal carcinoma tissues without liver metastasis, 30 with preoperative liver metastasis, 30 with postoperative liver metastasis and 30 surrounding normal colorectal tissues. And its correlation with gender, age, Dukes stages was analyzed too. RESULTS: The expression of COX-2 in colorectal carcinoma was significantly higher than that in surrounding normal colorectal tissue (P < 0.05), and meanwhile, its level in colorectal carcinoma without liver metastasis was significantly lower than those in tissues with preoperative or postoperative liver metastasis (P < 0.05). The COX-2 level had no correlation with gender, age, histological type, histological grade or the preoperative serum CEA and CA 19-9 levels in colorectal carcinoma (P > 0.05), but it was related to Dukes stages and lymph node metastasis. CONCLUSIONS: COX-2 plays a role in the course of generation, development and metastasis of colorectal carcinoma. The high expression of COX-2 in colorectal carcinoma tissues may be considered as an indicator for liver metastasis.

[Therapeutic effects of hepatic resection in liver metastasis of colorectal cancer].

OBJECTIVES: To evaluate therapeutic effects of hepatic resection in liver metastasis of colorectal cancer (LMCC). METHODS: The clinical data of 133 cases of LMCC received hepatic resection from January 1, 2000 to December 31, 2005 in Zhongshan Hospital were analyzed retrospectively. The relationship between hepatic resection and survival rate was also concerned. RESULTS: One hundred and thirty-three cases received curative hepatic resection in all 470 LMCC cases, of which 30 cases from synchronous liver metastasis (SLM) group (totaled 196 cases) and 103 cases from metachronous liver metastasis (MLM) group (totaled 274 cases). Mortality rate during operation was 3.3% in SLM and 1.9% in MLM (P < 0.05). All patients were followed-up till June 31, 2006, the 1, 3, 5 year survival rates and median survival time of SLM were similar to those of MLM, but its recurrence rate was higher (36.7% vs 20.4%, P = 0.030). The 1, 3, 5 year survival rate in the 49 patients who were operable but received non-operation treatment were significantly lower than those in operated patients (P = 0.003). In 30 SLM cases, 22 received I stage resection of their primary and liver metastasis tumor and 8 received liver metastasis resection after the primary surgery (II stage operation), 1, 2, 3 year survival and the median survival time were similar in the two groups. With COX multivariate analysis, incision margin > or = 1 cm (P = 0.036) and reoperation after recurrence (P = 0.041) were protective survival factors, and post-operation recurrence (P = 0.023) was survival risk factor. CONCLUSIONS: Curative hepatic resection is the first choice of therapy in liver metastasis of colorectal cancer and it can improve survival.

[Preoperative hepatic and regional arterial infusion chemotherapy in the prevention of liver metastasis after colorectal cancer surgery].

OBJECTIVE: To investigate the effects of preoperative hepatic and regional arterial infusion chemotherapy (PHRAIC) in the prevention of liver metastasis of colorectal cancer after surgery. METHODS: 110 patients of colorectal cancer underwent perfusion of 3 anti-tumor drugs into the hepatic artery and nutrient artery of the tumor respectively, radical surgery of the colorectal cancer 7 days after, and then general venous chemotherapy 3 weeks after operation, 112 patients underwent radical surgery of the colorectal cancer and general venous chemotherapy 3 weeks after operation. Follow-up was carried out every month with a follow-up period of 34 months +/- 3 months. RESULTS: There were no significant difference in post-operational complications between these 2 groups. The 3-year liver metastasis rate, 3-year tumor-free survival rate, overall survival rate, and median survival time of the stage III patients in the PHRAIC group were 12.7%, 82.3%, 87.7%, and 40 months +/- 5 months, all significantly better than those in the control group (28.3%, 58.7%, 75.5%, and 36 months +/- 3 months respectively, P < 0.05 or P < 0.01). CONCLUSION: PHRAIC reduces the liver metastasis of colorectal cancer after radical surgery and improves the survival of the stage III patients.