| BackgroundColorectal cancer is the most malignant tumors in digestive system. Neoadjuvant chemotherapy has received more and more attention, as a comprehensive treatment of tumors. Although there are so many ways to evaluate colorectal cancer, including RECIST which has widely used, there is lack of evaluation system and standards of colorectal cancer which is unified, targeted, and effective. And the increasing sophisticated molecular diagnostic technique provides us with a new way. If specific molecular markers were found to predict the efficacies of neoadjuvant therapy, it will lead far-reaching effect on evaluation and treatment of neoadjuvant chemotherapy.PurposeClinical research:we analyzed the clinical and pathological data of neoadjuvant therapy patients with colorectal cancer to explore the characteristics, efficacy evaluation, prognosis and the related factors in neoadjuvant chemotherapy patient. Experimental study:We used immunohistochemistry method and statistical analysis to explore the expression of TGOLN2and ZNF84in colorectal cancer and the relationship of clinic pathological data and to explore the expression of TGOLN2, ZNF84, MMP-9, MMP-14, VEGFC, CTHRC1and IRS-1in colorectal cancer of neoadjuvant chemotherapy patients and the relationship between the patients’base data and the effect of neoadjuvant therapy.MethodsA total of1791colorectal cancer patients, hospitalized in China-Japan Friendship Hospital, in the period of January2003and June2011, were studied. And92patients who used the neoadjuvant chemotherapy were selected in clinical study. Univariate analysis, paired T-test, and binary non-conditional logistic regression analysis, the Kaplan-Meier method, Cox single factor and multivariate regression were used to explore the efficacy evaluation effect of neoadjuvant therapy and the impact on the prognosis of patients. On the first part of the experimental study, a total of136patients, more than the5-year survival of less than2-year old, were selected to explore the expression of TGOLN2and ZNF84and its relationship of the clinical data. The second part of the experimental study, a total of18colorectal cancer patients who can be obtained pathology specimens of before and after neoadjuvant therapy, were chosen to explore the expression of the seven relative proteins on before and after neoadjuvant chemotherapy, and the relationship of the neoadjuvant treatment efficacy and patient clinical data.ResultsClinical research:The new adjuvant chemotherapy in patients with clinical remission accounted for63%, blood CEA remission for13.1%, primary tumor size in remission for33.6%, the depth of invasion accounted for13%.Overall merit:According to the curative effect evaluation, in these92neoadjuvant therapy patients, effective for63cases (68.5%), invalid for29patients (31.5%). The evaluation sensitivity, specificity, positive predictive value, negative predictive value, the correct rate, youden index, the re-evaluation of the kappa value, suggesting that infiltration depth (T stage) is one of the best evaluation. The neoadjuvant treatment may impact neutrophil count, red blood cell count, hemoglobin, platelet count, alanine aminotransferase, serum creatinine, albumin, triglycerides and maximum tumor size. Serum sodium (OR1.252,95%CI1.042-1.505, P=0.016); blood glucose levels (OR0.730,95%CI0.540-0.986, P=0.040) and different parts of the tumor incidence (OR5.490,95%CI1.574-19.149, P=0.008) could impact the effective of neoadjuvant treatment by using binary logistic regression analysis. Cox multivariate analysis indicated that the metastatic lymph node number (RR1.340,95%CI1.058-1.697, P=0.015) may be independent prognostic risk factors of patients with neoadjuvant therapy.The first part of experimental study:Higher than that of expression of TGOLN2in colorectal cancer, Para neoplastic (P<0.001), the ZNF84no significant difference (P=0.825); of ZNF84the positive expression of the patient’s gender (P=0.053), blood pressure (P=0.022).vascular tumor thrombus (P=0.041), logistic regression results suggest that hypertension (OR5.699,95%CI1.428-22.744, P=0.014) may affect ZNF84expression was independently associated factors. Univariate analysis found136patients in accordance with the survival of greater than5year survival of less than2years grouping, patient age (P=0.021), the degree of differentiation of cancer tissue (P<0.001), lymph node metastasis (P <0.001) and distant metastasis (P<0.001) may affect the prognosis; Multivariate analysis showed that the degree of tumor differentiation (OR0.847,95%CI,0008-0.847, P=0.036) and distant metastasis (OR0.033,95%CI0.003-0.352, P=0.005) for prognostic factors independently associated.The second part of experimental study:IRS-1(P=0.023), TGOLN2(P=0.028) after neoadjuvant therapy in the neoadjuvant therapy before the cancer tissues than ZNF84(P=0.576) and MMP-14(P=0.710) and MMP-9(P=0.151), VEGFC (P=0.779), CTHRC1(P=0.626) protein expression was no significant difference. Univariate analysis, the results suggest that TGOLN2possible with the length of the course (P=0.017), respiratory rate (P=0.012) and CA199(P=0.026); MMP-14may be associated with respiratory rate (P=0.001), neutral granulocyte count (P=0.008); CTHRC1with the red blood cell count (P=0.003), hemoglobin (P=0.048), platelet count (P=0.045), total bilirubin (P=0.004) and glucose (P=0.018); MMP-9may be associated with serum sodium (P=0.036).ConclusionsIn92neoadjuvant therapy patients, the effective one with63cases (68.5%), infiltration depth (T stage) may be the better indicators to evaluate the efficacy of neoadjuvant chemotherapy. Sodium, glucose, and tumor diseased parts may be the three separate factors affecting the efficacy of neoadjuvant chemotherapy. The expression of TGOLN2in colorectal carcinoma was higher than that in adjacent (P<0.001), and the expression of ZNF84had no significant difference (P=0.825). Hypertension may be the independent factors on the positive expression of ZNF84expression. The expression of IRS-1, and TGOLN2before neoadjuvant chemotherapy was higher than that after neoadjuvant therapy, before neoadjuvant chemotherapy was higher than that of neoadjuvant therapy.And it may be used as a reference index to determine the efficacy of neoadjuvant chemotherapy... |
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