الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Colorectal cancer (CRC) is a significant oncological and public health problem worldwide, being the third highest in incidence rate and the fourth highest in mortality rate. In Egypt, CRC represents 6.5% of all diagnosed cancer cases with a trend towards younger age at presentation. Regarding the recurrence of CRC, approximately 25% to 40% of patients who undergo curative resection of CRC develop tumor recurrence. Resection rates for recurrent lesions remain low (17.4%-54.8%) although survival benefits have been described.
Current modalities for post-operative CRC surveillance include clinical evaluation, radiological investigations such as chest and/or abdominal CT scan, invasive colonoscopy, and serum CEA being the only blood marker recommended in established guidelines for postoperative CRC surveillance, despite its low diagnostic performance. Emerging biomarkers have been studied in relation to post operative recurrence of CRC, among which is the trefoil factors family (TFFs) of proteins. The TFFs proteins play important roles in the mucosal protection and repair of epithelial surfaces as well as their involvement in the development and progression of various types of cancers. One of these factors is trefoil factor family-3 (TFF3) which is over expressed in a variety of human malignancies, including gastric, colorectal, mammary and prostatic malignancies.
The aim of the present work was to study serum TFF3 level in Egyptian CRC patients. Eighty subjects were included in the present study, divided into two main groups; group (I) consisted of 50 patients with histopathologically proven CRC subjected to tumor resection and receiving chemotherapy and group (II) consisted of 30 apparently healthy volunteers as a control group. Subjects with chronic kidney disease, other types of malignancies and gastrointestinal diseases were excluded from this study.
Retrospective gathering of clinical data, radiological and colonoscopy findings, results of histopathological examination and TNM staging of the tumor were done for all CRC cases. Laboratory determination of selected hematological and biochemical parameters including serum carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9) and serum TFF3 were done to all subjects included in the study.
The present study demonstrated a significantly higher serum TFF3 level in CRC patients subjected to tumor resection compared to control group. Furthermore, serum TFF3 level was significantly higher in CRC cases initially presenting with metastatic spread to both liver and lungs compared to CRC cases with liver metastasis only. As a prognostic marker of early recurrence, serum TFF3 was significantly higher in cases that developed recurrence within a year of follow up whether local or distant than those whom did not develop recurrence. In addition, the prognostic value of serum TFF3 to predict an early as one year recurrence was studied using ROC curve analysis. The generated cut-off value for serum TFF3 as a marker of recurrence was 10.845 ng/mL, which gave a sensitivity of 78.57%, specificity of 61.11%, positive and negative predictive values of 44.0% and 88.0% respectively. Serum TFF3 level showed significant positive correlation with age, tumor recurrence and CEA concentration. Multiple regression analysis demonstrated that age, tumor recurrence and serum CEA level were positive contributors that could influence serum TFF3 level.
Summary and Conclusion
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In conclusion, the prognostic value of serum TFF3 as a biomarker of early recurrence in tumor resected CRC cases could represent a step in the search for non-invasive lab biomarkers other than the traditionally used tumor markers (CEA and CA19.9) in follow up of recurrence in CRC.
Recommendations
Based on the results of the present study, the following could be recommended:
1. Confirming the prognostic value of serum TFF3 as a reliable biomarker of early recurrence in future multi-center studies on a larger sample size of non tumor resected CRC cases that are to be followed up post tumor resection till development of recurrence.
2. Conducting tissue based studies for TFF3 messenger ribonucleic acid (mRNA) and protein expression in tumor resected cases that experienced tumor recurrence and correlating it with serum TFF3 level in such cases.
3. Conducting studies concerning the use of TFF3 as a therapeutic modality aiming at preventing or delaying the recurrence of CRC thus reducing the burden of disease related morbidity and mortality in such cases.
4. Assessing serum levels of TFF1 and TFF2 in relation to tumor recurrence in tumor resected CRC patients.