الفهرس | Only 14 pages are availabe for public view |
Abstract Colorectal cancer remains a common lethal cancer worldwide, ranking as the third most frequently diagnosed cancer and the second in mortality. However, CRC outcomes could be improved by early diagnosis. Current diagnostic methods include non-invasive tests limited by their inadequate performance and invasive ones limited by patient noncompliance. Tumour microenvironment consisting of tumour cells and attracted immune cells plays a significant role in CRC pathogenesis. These cells secrete inflammatory mediators such as eotaxin-1, macrophage-inflammatory protein-1 beta (MIP-1β), granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor A (VEGF-A) and Fas ligand (FasL) which can promote tumour growth, progression and metastasis. Profiling these mediators in a heterogeneous disease like CRC is needed rather than a single biomarker measurement. The present study aimed to evaluate the utility of serum profiling of eotaxin-1, MIP- 1β, G-CSF, VEGF-A and FasL as potential biomarkers in colorectal cancer using multiplex bead assay, in addition to evaluation of their serum levels in non-cancerous patients complaining of gastrointestinal symptoms. The study was conducted on 87 Egyptian patients complaining of gastrointestinal symptoms. Patients with known malignancy other than colorectal and who had a history of colorectal cancer therapy were excluded from the study. Based on colonoscopy findings; patients were divided into 35 CRC and 52 non-malignant patients. Non-malignant patients were further subdivided into 9 with colon polyp, 24 with inflamed mucosa (colitis) and 19 with normal mucosa. 15 CRC patients had undergone surgical resection in MRI and their metastatic status were obtained from MRI pathology unit records. Bead-based multiplex assay was used for serum profiling of eotaxin-1, MIP-1β, G-CSF, VEGF-A and FasL. In the present work, the median value of eotaxin-1 in CRC patients was significantly higher than its corresponding median values in non-malignant group and than its corresponding median values in both colitis and control groups. As regards serum MIP-1β, CRC patients also had a significantly higher median value than the corresponding nonmalignant group, colitis and control groups. Concerning serum G-CSF and VEGF-A, CRC patients had significantly higher median values than the corresponding non-malignant group, colitis, polyp and control groups. Finally, there was no statistically significant difference between the median values of FASL in CRC and non-malignant groups. Also, the studied combined biomarkers (eotaxin-1, MIP-1β, G-CSF and VEGF-A) showed better discriminatory power than that of routinely used stool occult blood to discriminate between colorectal cancer and non-malignant cases. In conclusion, this study supports studies suggesting serum profiling of eotaxin-1, MIP-1β, G-CSF and VEGF-A as potential biomarkers in early CRC diagnosis. The studied panel of biomarkers could be combined with stool occult blood to reduce false positives rates and unneeded colonoscopy and biopsies. Using multiplexing bead technology is needed rather than using a single biomarker measurement and could represent a promising approach for CRC screening in high risk patients, CRC diagnosis and personalized medicine implementation. Summary, Conclusion & Recommendations 85 Recommendations In order to continue future research in that field we recommend the following: 1. Conducting such a study on a larger sample size of Egyptian CRC patients to confirm the role of the panel of eotaxin-1, MIP-1β, G-CSF and VEGF-A in early CRC diagnosis. 2. Follow up of the patients to detect the role of eotaxin-1, MIP-1β, G-CSF and VEGF-A in CRC recurrence and prognosis. 3. Further studies are needed to assess serum levels of eotaxin-1, MIP-1β, G-CSF, VEGF-A and FasL in different CRC stages and comparing their levels in metastatic and non-metastatic patients. 4. Determination of the possible role of eotaxin-1, MIP-1β, G-CSF and VEGF-A in targeted therapy approaches and precision medicine implementation aiming at reducing the burden of CRC morbidity and mortality. 5. Further studies are needed to assess serum levels of eotaxin-1, MIP-1β, G-CSF, VEGF-A and FasL in CRC patients after initiation of chemotherapy regimens to detect their roles in follow up for currently used chemotherapy regimens. 6. Conducting such a study on subjects with hereditary predisposition for CRC including: family history of CRC and hereditary CRC syndromes to detect the predictor role of the panel for CRC incidence. 7. This combined panel of markers could be combined with stool occult blood and added to the guidelines for early CRC diagnosis to reduce the number of unnecessary colonoscopies. |