Expression of Breast Cancer Subtypes Based on the Most Important Biomarkers: Comparison of Clinicopathological Factors and Survival

Hadizadeh, Mohammad; Arani, Hamid Zaferani; Olya, Maedeh

doi:10.5812/ircmj.57931

Cited by 2 publications

(1 citation statement)

References 39 publications

(41 reference statements)

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“…Immunotoxins are composed of a toxin that joins to antibodies targeting antigens existing on cancer cells' surface (3). According to molecular analyses, breast cancer is classified into multiple intrinsic groups such as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-positive, basal-like (triple-negative), erb-B2, and normal breast-like (4). Among these subtypes, nearly 15% to 20% of patients with breast cancer are HER2-positive as diagnosed by the overexpression of HER2 receptors and/or HER2 gene amplification.…”

Section: Introductionmentioning

confidence: 99%

In Silico Design and Evaluation of scFv-CdtB as a Novel Immunotoxin for Breast Cancer Treatment

et al. 2020

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Background: Breast cancer is the most prevalent type of cancer among the female population, and about 15% to 20% of patients with breast cancer is human epidermal growth factor receptor 2 (HER2)-positive. The current cancer treatment methods such as surgery, radiation, and chemotherapy are not sufficiently effective in decreasing mortality rates; however, immunotherapy is a novel approach in the treatment of cancer that is more efficient and less harmful to the body. Anti-cancer immunotoxins are chimeric molecules containing two parts, namely the immuno part, which is an antibody or a binding segment of antibody, and toxin part, which is a killer toxin molecule. Objectives: In this study, we sought to design a novel immunotoxin, including the anti-HER2 receptor, trastuzumab, derived from a single-chain variable fragment (scFv) with a connection to the functional part of Campylobacter jejuni cytolethal distending toxin (Cj-CdtB). Methods: The chimeric protein's physicochemical properties, solubility, and secondary structure were analyzed, using ProtParam, PROSO II, and GORV, respectively. A three-dimensional (3D) model was built, using I-TASSER and refined, using GalaxyRefine. The model's structure was evaluated before and after refinement, using PROCHECK and RAMPAGE. The AlgPred server was employed to predict immunotoxin allergenicity, and mRNA stability was evaluated by RNAfold. Finally, the immunotoxin and HER2 were docked, using ZDOCK. Results: Analysis showed that the chimeric protein could be a stable and soluble protein and the secondary structure of its parts would not change and the protein had a robust 3D structure that might have a stable mRNA structure and could bind to HER2 receptor. Conclusions: The designed immunotoxin was a stable and soluble protein with the ability to bind to HER2 receptors, making it an appropriate immunotoxin candidate for breast cancer treatment. The results of the current work could be useful for future experimental studies.

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Section: Introductionmentioning

confidence: 99%