Correlation Analysis Between TAP(Tumor Abnormal Protein) And Chemotherapeutic Effect In Colorectal Cancer

Background In recent years, colorectal cancer has been one of malignant tumor with the most rapidly rising morbidity and mortality. Colorectal cancer(CRC) early diagnosis is low, and has very frequent recurrence or metastasis after surgical excision. It is a big problem to diagnose early and monitor recurrence or metastasis in CRC. In all kind of methods used to screen for CRC, detection of cancer markers is more convenient and has strong indicative relatively. At present, no ideal serological biomarkers in diagnosis and monitor of CRC, so looking for a convenient and effective serological biomarker is particularly important. In order to provide basis for clinical early detection and early treatment, we detected the expression level of tumor abnormal protein(TAP) in peripheral blood of CRC patients before chemotherapy; explored the correlation between the expression of TAP in peripheral blood of CRC patients and clinicopathologic characteristics. To explore the value of TAP on evaluating the curative effect of chemotherapy in CRC patients, we discussed the correlation between expression of TAP in advanced CRC patients and chemotherapeutic(based on PEM) response. The key points of our study were detected the expression of serum TAP in CRC patients with different prognosis, investigate the influence of TAP on CRC patients prognosis; compared TAP with some common serological biomarkers(e.g. Carcinoembryonic Antigen(CEA), Carbohydrate Antigen 125(CA125), Carbohydrate Antigen 19-9(CA19-9) and alkaline phosphatase(ALP)) and explore the correlation between each other. We also investigated the association between the clinicopathologic characteristics and the variation of TAP expression in CRC patients after chemotherapy.Materials and Methods Patients(N=98) were enrolled into this study with histologically or cytologically confirmed CRC. All patients enrolled were inpatients from Sept 2014 to Feb 2015 diagnosed in Jiangsu Cancer Hospital, and blood collected before and after chemotherapy. According to the treatments, all patients were divided into two groups, group A and B. 30 patients in group A were postoperative CRC patients accepted adjuvant chemotherapy which was predominantly FOLFOX; the rest 68 patients in group B were advanced CRC patients, who accepted palliative chemotherapy based on PEM. We also collected demographic characteristics, clinicopathologic characteristics and laboratory indexes by looking up medical records. The reference range of TAP were: normal TAP/no condensate: 0-121μm2; abnormal TAP/smaller condensate: 121-225μm2; abnormal TAP/bigger condensate: ≥225μm2. All blood samples were examined with TAP testing kit, then a multistage coupling reaction between serum TAP and lectin happened by agglutination method. We measured the area of condensate by TAP detection system image analyzer to calculate the expression of TAP in peripheral blood of CRC patients. By comparing the change of TAP before and after adjuvant chemotherapy, we explored the correlation between the expression of TAP and clinicopathologic characteristics in group A. We discussed more beyond that in group B. In addition to CT(computed tomography) and MRI(magnetic resonance imaging) detection, we discussed the correlation between expression of TAP in advanced CRC patients and chemotherapeutic response, to explore the value of TAP on evaluating the curative effect of chemotherapy(based on PEM) in advanced CRC patients. The study data was analyzed through the STATA 10.0 software. Continuous variables were summarized by descriptive statistics, categorical variables by frequency. Count data by Chi-square test; measurement data as mean ± standard deviation. Regression analysis was used to compare TAP and some other serological biomarkers and investigate the association between the raise of TAP and curative efficacy. Correlate analysis and Spearman rank correlation analysis were used to analysis the factors effected the change of TAP. p<0.05 was considered statistically signifcant.Results(1) The positive rate of serum TAP in both group A and B before chemotherapy were 100%. No significant differences between TAP and some other serological biomarkers(e.g. CEA, CA125, CA19-9 and ALP) in patients in two groups before chemotherapy.(2) Before patients in group A accepted chemotherapy, TAP in serum has no significant difference with clinicopathological characteristics(e.g. age, sex, tumor differentiation and dukes classification)(p>0.05); the TAP expression level in group B patients before chemotherapy had a significant correlation with degree of cancer differentiation(p<0.05), but had no significant correlation with other clinicopathological characteristics(e.g. age, sex and presence of distant metastasis)(p>0.05). The worse histologic classes, the higher positive expression rate of serum CEA and CA19-9 in group A patients, and the difference was statistically significant(p<0.05). The expression of serological biomarkers e.g.CEA,CA19-9, CA125 and ALP in group B patients had no significant difference with clinicopathological characteristics(e.g. age, sex, tumor differentiation and presence of distant metastasis)(p>0.05).(3) The expression of TAP significantly decreased in group B patients with curative effect and TAP significantly increased in patients who accepted palliative chemotherapy(based on PEM) with poor response(p=0.000). The variation of other serological biomarkers were also positively associated with the chemotherapy response, while in all these biomarkers only CEA and CA19-9 had significant differences(p=0.0003, p=0.009).(4) After palliative chemotherapy(based on PEM), poorly differentiated CRC was positively correlated with TAP expression elevated(p=0.024). In group A patients, no correlation was found among increasing rate of TAP and clinicopathological characteristics e.g. age, sex, tumor differentiation and dukes classification(p>0.05). Correlation analysis were used to find out association between the raise of TAP and those clinicopathological characteristics, and reminded the poorly differentiated histological type show biggest impact on the expression of TAP in both group A and B patients after chemotherapy.Conclusions(1) The expression of TAP showed strong positive as 100% in both group A and group B patients. The expression of TAP between group A and group B patients showed no significant difference. Before patients accept chemotherapy, the expression of TAP showed no significant association with other serological biomarkers(e.g. CEA, CA125, CA19-9 and ALP).(2) In our study, we observed the expression of TAP in advanced CRC patients after palliative chemotherapy was associated with curative effect of CRC. The expression of TAP significantly decreased in responders and TAP significantly increased in group B patients with poor response. So, the increase of TAP after may predict poor outcome in advanced CRC patients.(3) Pathological differentiation is an extremely important factor in influence curative effect of CRC patients(both postoperative patients and advanced patients), which should be taken full consideration in chemotherapy of CRC patients.