الفهرس 
TitleOnly 14 pages are availabe for public view
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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
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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.