| 【Background】MGb2, a mouse derived monoclonal antibody specific to gastric carcinoma, was developed in our laboratory using the technique of hybridoma. Previous studies confirmed that MGb2 antigen (MGb2-Ag) had excellent diagnostic and prognostic value for gastric cancer patients. Recently, we have identified TRAK1 as MGb2-Ag. However,the role of MGb2-Ag in colorectal cancer (CRC) is still unclear.【Objectives】1. To investigate the expression of MGb2-Ag in CRC tissue.2. To investigate the relationship between MGb2-Ag expression and the overall survival rate of CRC patients.3. To detect the impact of MGb2 antibody on apoptosis of gastrointestinal carcinoma cells.【Methods】1. Immunohistochemistry was used to detect MGb2-Ag expression in 140 CRC tissues. 2. The relationship between MGb2-Ag expression and clinicopathological characteristics were statistically analyzed.3. Using clinical follow-up and survival analysis to find which factors were associate with survival time of CRC patients.4. Western blotting was used to detect expression of MGb2-Ag in both CRC tissues and cells.5. The subcellular localization of MGb2-Ag in cells was performed by immunofluorescence staining using a laser scanning confocal microscope (LSCM).6. Flow cytometer (FCM) was used to detect the effect of MGb2 antibody on apoptosis of AGS cell line.【Results】1. MGb2-Ag expression in CRC tissues was significantly higher than in normal tissue. 20 (14.29%) cases showed negative staining (-), 65 of 140 (46.43%), 40 of 140 (28.57%) and 15 of 140 (10.71%) cases were scored as weak positive staining (+), moderate positive staining (++) and strong positive staining (+++).2. MGb2-Ag was positively correlated with tumor differentiation (p = 0.006), invasion (p = 0.049) and pathological stage (p = 0.032). There was no significant difference between MGb2-Ag expression and the age or gender of the patient, lymphatic invasion or distant metastasis (p = 0.586, 0.308, 0.910, and 0.068, respectively).3. Kaplan–Meier analysis revealed that the prognosis of CRC patients was significantly related to MGb2-Ag expression level (log-rank test: p < 0.001). The postoperative mean and median survival times of all CRC patients were 41.011±1.75 and 50 months, respectively. The mean survival time of patients with negative (-) MGb2-Ag expression was 48.7±3.934 months. The mean survival times of patients with weak positive (+) MGb2-Ag expression, moderate positive (++) MGb2-Ag expression and strong positive (+++) MGb2-Ag expression were 44.57±2.19 months, 34.76±2.8 months and 19.53±4.24 months, respectively. Univariate analysis revealed that high MGb2-Ag expression, tumor differentiation, invasion, distant metastasis and clinical stage were significantly associated with the survival time of CRC patients.In multivariate analysis, the adjusted HR was 1.00 (as a reference) in the MGb2-Ag negative (-) expression group, and the adjusted HRs of weak positive (+), moderate positive (++), and strong positive (+++) groups were 1.328 (p = 0.532), 2.88 (p = 0.019) and 6.7509 (p < 0.001), respectively. The survival time of CRC patients with high expression of MGb2-Ag was shorter than the survival time of patients with low MGb2-Ag expression. Both univariate and multivariate analyses showed that tumor differentiation and MGb2 expression were two independent and prognostic factors for CRC (p < 0.001).4. MGb2-Ag was highly expressed in SW480, SW620 and HT-29 cells. The highest expression of MGb2-Ag was observed in SW480. But it was weak to absent in HIEC. The cell and tissue MGb2-Ag expression pattern was highlighted by two bands at approximately 100 and 120 kDa.5. MGb2-Ag was primary localized in the cell membrane.6. MGb2 antibody could induce apoptosis of AGS.【Conclusions】1. The expression of MGb2-Ag in CRC was firstly detected by our group and we found that it can serve as a valuable prognostic indicator of CRC. 2. The cell and tissue MGb2-Ag expression pattern, highlighted by two bands at approximately 100 and 120 kDa, was consistent with the expression pattern observed in gastric cancer which suggested that MGb2-Ag may play an important role in the development of CRC.3. We firstly found that MGb2-Ag was primary localized in the cell membrane, and MGb2 antibody could induce early apoptosis of AGS which will be beneficial to the research of molecular targeted therapy drugs. |
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