| ObjectiveIn order to search for new molecular markers as prognostic factors for colorectal adenocarcinoma and to provide more information for clinical practice, guiding treatment and reducing recurrence and metastasis, the following biological markers as CD133, CD147, EphA3, LRP16 and Ki-67were investigated, furthermore, their relevance to tumor biological characteristics and diseases free survival(DSF) of patients were analyzed.To provide more information for clinical diagnosis of colorectal adenomas and guiding treatment, CD 133 and p53 protein were investigated. Their correlation with above markers and the relationship between both markers and tumor biological characteristics were analyzed.Materials and methods(1) Follow-up was taken among 201 patients with colorectal carcinoma from archival files of Chinese People's Liberation Army (PLA) General Hospital during 1999-2003. And all 201 cases of colorectal carcinoma tissues were made into 12 tissue microarrays by hand. Expressions of nine biologic markers, CD 133, EphA3, LRP16 and Ki-67, were detected in the tissue microarrays by PV-9000 immunohistochemical method. Their relationships between clinicopathologic features and prognosis were analyzed, afterwards. One hundred seventy-two colorectal adenomas in PLA General Hospital during 2004-2009 were collected and reviewed by surgical endoscope resection. CD 133 and p53 expression were detected in 172 cases of colorectal adenomas by PV-9000 immunohistochemical method. Their relationships between clinicopathological features and prognosis were also analyzed.(2) The differential expression of CD133 and EphA3 were detected in 20 cases of colorectal carcinoma and normal mucosa beside the carcinomas by Western Blot.(3) The differential expression of CD133mRNA were detected in 18 cases of colorectal carcinoma and normal mucosa beside the carcinomas by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)Result(1) The expressions of CD133, CD147, EphA3, LRP16 and Ki-67 were increased gradually with the depth of invasion and the number of lymph node involvement (P< 0.05). The positive expressions of CD133, CD147, LRP16 and Ki-67 in tumors with abdominal and distant metastasis were markedly higher than in those without (P<0.05). The expressions of CD 133, CD147, EphA3, LRP16 and Ki-67 were increased gradually, corresponding to TNM stage from I to IV (P＜0.05). The expressions of CD147, LRP16 and Ki-67 showed a positive correlation with the histological grade (P＜0.05).(2) The Ki-67 expression in colorectal adenocarcinoma were positively correlated with the expressions of CD133, CD147 and LRP16 (r=0.498, r=0.380, r=0.394, P＜0.05).(3) The expression of CD 133, CD 147, EphA3, LRP16 and Ki-67 in carcinoma was significantly higher than that in adjacent normal mucosa (P<0.05),(4) By univariant survival analysis, the expressions of CD133, CD147, EphA3, LRP16 and Ki-67, macroscopic type, degree of differentiation, infiltrative deepth, lymphatic invasion, abdominal and distant metastases and TNM stage were significantly correlated with prognosis (P<0.05).(5) By Cox multivariant survival analysis, the negative expressions of CD 147 and LRP16, lower degree of differentiation, shallower of invasion, nonmetastases and lower TNM stage were correlated with a longer survival time and better prognosis (P<0.05).(6) The protein extracted from colorectal adenocarcinoma and normal mucosa beside the carcinomas was identified by Western Blot with CD 133 and EphA3 binding activity. The expression of CD 133 and EphA3 in colorectal adenocarcinoma was higher than that in normal mucosa beside the carcinomas by Western Blot (P＜0.05)(7) The expression of CD133mRNA in colorectal adenocarcinoma was significantly higher than that in adjacent normal mucosa by RT-PCR (P<0.05).(8) The expression of CD 133 and p53 in colorectal adenoma was related to tumor size, grade of dysplasia and histological type (P＜0.05).(9) The CD 133 expression was positively correlated with the Ki-67 expression in colorectal adenoma (r=0.344, P<0.05).(10) The expression of CD133 and p53 in colorectal adenoma was significantly higher than that in normal mucosa (P＜0.05).Conclusions(1) The expressions of CD133, CD133, CD147, EphA3, LRP16 and Ki-67 may be significantly correlated with prognosis, The Ki-67 expression was related to the expression of CD 133, CD 147 and LRP16.(2) CD 147, LRP16, differentiation, infiltrative depth, abdominal and distant metastases and TNM stage may be independent prognostic factors for survival of colorectal adenocarcinoma.(3) The expressions of CD 133, CD 147, EphA3, LRP16 and Ki-67 were related to tumor development and distant metastasis. It is suggested that the expressions of above-mentioned biologic markers may play an important role in the development and progression of the tumor and thus become new prognostic markers for colorectal adenocarcinoma.(4) CD 133 and p53 play an important role in the development and progression of colorectal adenoma. They may become new prognostic markers for colorectal adenoma, which may display an important function in tumorigenesis of colorectal mucosa.
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