Journal Article

Genetic insights and therapeutic potential for colorectal cancer: mutation analysis of KRAS gene and efficacy of Oleuropein-conjugated iron oxide nanoparticles

Peymani, Maryam, Zaefizadeh, Mohammad, Salehzadeh, Ali, Mehdinejad, Sedigheh

2024

Overview

This study aimed to address the challenges of treating advanced stages of colon cancer (CRC) by exploring potential therapeutic options. The research focused on the genetic aspects of CRC, specifically the mutation rate of the KRAS gene, along with other genes like TTN , APC , MUC16 , and TP53, using the TCGA dataset. Additionally, the study investigated the efficacy of Oleuropein, a polyphenolic compound found in olives, in combating CRC by using iron oxide nanoparticles coated with glucose and conjugated with Oleuropein. The study characterized the physicochemical properties of the nanoparticles, and the cytotoxic effects of the nanoparticles were evaluated on CRC and normal fibroblast cell lines, demonstrating significantly higher cytotoxicity against CRC cells compared to normal cells. Furthermore, the study analyzed gene expression changes using the GSE124627 dataset to understand the influence of KRAS alterations. It identified numerous upregulated and downregulated genes in KRAS-overexpressing samples, suggesting their involvement in critical cancer-related pathways. These findings suggest that KRAS -influenced genes could serve as potential therapeutic targets for CRC treatment. The study also examined the expression levels of identified genes in CRC samples compared to normal samples. Among the upregulated genes, 22 showed significant increases in cancer samples, while 14 downregulated genes exhibited decreased expression in both KRAS-influenced and cancer samples. Cox regression analysis identified specific upregulated genes, including ANKZF1 , SNAI1 , PPFIA4 , SIX4 , and NOTUM , associated with poor prognosis. Kaplan-Meier analysis further confirmed the correlation between increased expression of these genes and higher patient mortality rates. In conclusion, this study provided valuable insights into the genetic aspects of CRC and potential therapeutic strategies. The use of Oleuropein-conjugated iron oxide nanoparticles showed promising cytotoxic effects on colon cancer cells. These findings contribute to advancing our understanding of CRC and offer potential targets for further investigation and the development of novel therapeutic approaches.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adenomatous polyposis coli / Antineoplastic Agents - pharmacology / Biomedical and Life Sciences / Biomedicine / Cell Line, Tumor / Cell Survival - drug effects / Colon cancer / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - genetics / Colorectal Neoplasms - pathology / Cytotoxicity / DNA Mutational Analysis / Down-regulation / Ferric Compounds - chemistry / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Genes / Genetic analysis / Humans / Iridoid Glucosides - pharmacology / Iridoids - pharmacology / Iron oxides / K-Ras protein / Mutation / Mutation rates / Nanoparticles / Neurosciences / p53 Protein / Pharmacology/Toxicology / Physicochemical properties / Proto-Oncogene Proteins p21(ras) - genetics / SIX gene family / Snail protein / Therapeutic targets