الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy and the third most common cancer globally. In Egypt, CRC represents 6.48% of total malignancies. Antiapoptotic proteins play a critical role in the survival and proliferation of cancer cells, including colon cancer cells. These proteins inhibit apoptosis, which is a natural process of programmed cell death that helps to eliminate damaged or abnormal cells. By inhibiting apoptosis, cancer cells can evade cell death and continue to proliferate, contributing to tumor growth and progression. Targeting antiapoptotic proteins is a promising strategy for improving the efficacy of colon cancer treatment.
Ras-related C3 Botulinum Toxin Substrate (RAC3), Prolyl 4hydroxylase beta polypeptide (P4HB) and B cell lymphoma 2 (BCL2) are different proteins which play role in cancer colon development by inhibition of apoptosis and by other different mechanisms.
The current study aimed to evaluate the role of RAC3, P4HB and BCL2 in pathogenesis of CRC and to assess their prognostic impact on CRC patients by studying their relationship with clinicopathological parameters and survival data.
This retrospective case control study involved 174 cases, divided into 38 non neoplastic colonic specimens (control specimens), 23 adenoma specimens and 113 CRC specimens retrieved from the archival of Pathology Departments of Faculty of Medicine Menoufia University during the period between 2018 and 2021. Hematoxylin and eosin (H&E) stained slides of the selected cases’ blocks were examined carefully to identify viable and representative areas of each sample.
Tissue microarray technique was performed through sampling of three cores of representative areas of the tumor and stroma from each specimen.
RAC3 is an oncogene that contributes to tumor development by regulating several transcription factors that control the expression of genes related to cell cycle progression and proliferation, inhibition of apoptosis, autophagy and senescence which can contribute to tumor formation.
P4HB acts as an endoplasmic reticulum chaperone to suppress aggregation of misfolded proteins preventing ER stress and protein misfolding. It plays a role in the regulation of the generation of reactive oxygen species (ROS) that regulates the apoptosis of cancer cells, and its overexpression promotes cell growth, proliferation, migration, invasion, and epithelial-to-mesenchymal transition.
The expression of RAC3 and P4HB showed a significant difference between the studied groups. Neoplastic specimens (adenoma and CRC) had significantly higher positive expression of RAC3 and P4HB compared to non-neoplastic specimens.
High RAC3 and P4HB expression in adenoma showed significant association with poor prognostic clinicopathological parameters as age <47.65 years, tubulo-villous adenoma (RAC3), villous adenoma (P4HB), adenoma with high grade dysplasia, adenoma with size >2cm and advanced adenoma.
High RAC3 an P4HB expression in CRC showed a statistically significant association with poor prognostic clinicopathological parameters as young age, right colonic carcinoma, presence of gross perforation, large tumor size, advanced pathologic T stage, Positive LN involvement , presence of distant metastasis, advanced stage group, poorly differentiated tumor, high grade tumors, rN3, mucinous adenocarcinoma, presence of lympho-vascular invasion (p<0.001), presence of perineural invasion, involved margins , high mitotic count, low apoptotic count, high tumor budding score, high tumor-stromal ratio and infiltrating TBC.
Moreover, dead patients and cases that showed progression had high RAC3 and P4HB expression compared to alive cases and cases that showed no progression.