Role of Mitochondria-Related Genes in Cancer Incidence

Abstract

Cancer is a group of diseases involving the uncontrolled growth and spread of cells with the potential to invade and spread to other parts of the body. As the second leading cause of mortality worldwide, early diagnosis is crucial for improving patient prognosis and survival rates. Despite recent advancements, there remains a shortage of effective biomarkers for early detection of the cancer.
The main aim of this research is to investigate the association of important SNPs in mitochondria- related genes and cancer incidence. Focusing on previously identified three cancer causing genes - FDPS, HSCB, NSUN4 -genotyping was performed on a cohort of 3,500 participants. Furthermore, in a cell culture study, we investigated the impact of SNPs on the expression of their corresponding genes and compared the expression levels between cancerous and non-cancerous cell lines.
The findings show that SNP in HSCB gene had a significant association with cancer incidence, though this was not consistent across specific cancer types. Notably, SNP in the NSUN4 gene was associated with a significantly lower risk of digestive system cancers, but with an increased risk of respiratory system cancers. However, FDPS gene was not associated with incidence of any cancer type investigated in this study. Gene expression analysis showed that the TTC28 which harbors the SNP influencing the mitochondria-related HSCB gene had significantly lower expression in both triple negative and non- triple negative cancer cells compared to non-cancer cells. These results suggest that it may have a protective role in cancer. However, the HSCB gene expression showed the opposite trend. No firm conclusions could be drawn from FDPS and ASH1L (which harbors the SNP) gene expression patterns. The genotyping of cell lines showed that mutated form of the FDPS and HSCB genes was commonly present in the more aggressive form of breast cancer (triple-negative breast cancer).
In conclusion, this study highlights the complex roles of mitochondrial-related genes in cancer. HSCB and NSUN4 have a potential to be used as a biomarker in cancer, however, further research is needed to validate these findings and to explore their clinical applications.

Popular Abstract

Mitochondria are famously known as the powerhouse of the cell; however, their significance extends far beyond energy production. Mitochondrial dysfunction is involved in a variety of diseases, including metabolic disorders, age-related conditions, neurogenerative diseases, and cancer. While the association between mitochondria and cancer has been extensively researched, much remains to be understood about this complex relationship. Recent research findings suggest that these organelles may hold the key to earlier cancer diagnosis, potentially transforming patient outcomes.
Cancer remains one of the leading causes of death worldwide, second only to heart disease. This raises a critical question: why don't we have a cure for cancer? Despite significant advances in medical research, curing cancer is challenging due to the disease's complexity. However, early detection of cancer is crucial, as it improves patient survival rates and treatment efficiency. It is well known that molecular changes appear earlier than the clinically visible cancer on current diagnostic methods. The goal is to detect these molecular changes early by biomarkers, which help clinicians to diagnose and predict disease outcomes. Considering the heterogenous nature of cancer, developing effective biomarkers is challenging, and despite extensive research, there are still only a few reliable markers compared to the numerous types of cancer. Given the important role mitochondria in cancer, it is important to approach this issue on the molecular basis of mitochondrial function.
This research project aims to explore the role of mitochondria-related genes in cancer. Previous studies have identified three mitochondria-related genes - FDPS, HSCB, and NSUN4 - as having potential links to cancer pathogenesis. However, to the best of our knowledge, their role as predictive biomarkers is not known. This study aimed to investigate these genes in a population-based study of middle-aged women in Sweden. Normally every gene has two alleles, which can be either wild-type, mutated, or a combination of both. Mutations often involve the substitution of one nucleotide for another, and these changes are called single nucleotide polymorphism which were the focus of the study. DNA samples from 3,500 participants were analyzed by a method called genotyping, which identifies these allelic differences. Participants health was followed for 20 years, some of them had developed cancer and some were cancer free, allowing to link specific gene mutations to occurrence of cancer. Additionally, the gene expression patterns were examined in various cell lines, both cancerous and non-cancerous, to better understand the role of these genes.
We found that HSCB, TTC28 and NSUN4 genes had the potential to be used as cancer biomarkers, although further research is needed to confirm these findings. If validated, these genes could serve as new biomarkers for early cancer detection. All things considered, this research project emphasizes of the importance of mitochondrial genetics as the link to improving early cancer detection and patient outcomes worldwide.

• author: Laas, Irma
• supervisor: Ashfaque Memon
• organization: Pure and Applied Biochemistry
• course: KBKM01 20241
• year: 2024
• type: H2 - Master's Degree (Two Years)
• subject: Medicine and Health Sciences
• keywords: Cancer, mitochondria-related genes, biomarkers, genotyping, gene expression, applied biochemistry
• language: English
• id: 9161797
• date added to LUP: 2024-06-13 09:48:21
• date last changed: 2024-06-13 09:48:21