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Investigation of expression and methylation profiles of KIFC1 protein in patients with lung cancer

2022
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Advisor: Prof. Dr. Necat Vakur Olgaç

Abstract (EN)

Lung cancer is the most common cancer, ranking first in cancer-related deaths. Despite the discovery of biomarkers and targeted agents for the diagnosis, treatment, and follow-up of lung cancer, it is still a leading cause of cancer-related deaths in our country and the world. Thus, there is a need for new mechanisms to elucidate the molecular mechanisms of lung cancer. While the functional role of the kinesin family member (KIFC1) in normal cells is debated, it has been reported to play an effective and crucial role in malignant cell survival in many cancers. The KIFC1 protein plays a critical role in centrosome clustering and microtubule dynamics in cancer cells and is essential for the survival of malignant cells that escape apoptotic cell death. To determine whether KIFC1 protein can be used as an invasive or noninvasive biomarker in lung cancer, this study examined the expression and methylation of 39 patients with diagnosed lung cancer, tumor tissue and tumor-conjugated normal tissue, serum, and lymphocytes, as well as lymphocyte and serum samples from healthy controls. KIFC1 gene expression was compared in tissue and lymphocyte samples using the qRT-PCR method. The methylation-specific PCR(MSP) method was used to determine methylation status. The study analyzed the increase/decrease in expression level, methylation profiles, and clinical and pathological characteristics of the patients using statistical methods. Unmethylation was detected in 95.8% (23/24) of 62.1% (24/37) patients with increased KIFC1 gene expression. When the mean fold & change values of tumor and conjugated normal tissue samples of the patients were compared, the expression level of KIFC1 gene was found to be increased 3.2-fold in tumor tissue compared to conjugated normal tissue. When the Fold&Change values of the patient serum samples were compared with the healthy serum samples, it was found that the expression level of the KIFC1 gene was increased 2.4-fold in the patient serum compared with the healthy serum. At the same time, statistical significance was found between KIFC1 expression and metastasis (p=0.013), tumor stage (p=0.040), and tumor grade (p=0.010) when patients' clinical parameters and methylation and expression results were statistically compared. KIFC1 gene expression is thought to be more elevated in patients diagnosed with lung cancer than in the healthy population, so KIFC1 gene expression and methylation status can be used as biomarkers for lung cancer screening. In addition, it can be assumed that the methylation profile of the KIFC1 gene could be a potential biomarker for determining the squamous cell lung cancer subtype of lung cancer. The results of the study need to be followed up by analysis of a larger number of patients.

Author

Dr. Betül Çelik

How to Cite

Betül Çelik (Doctorate thesis). Investigation of expression and methylation profiles of KIFC1 protein in patients with lung cancer, 2022, İstanbul University.

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