The Identification of Cytochrome B5 Reductase 2 and Fructose-1,6-Bisphosphatase 1 Proteins in Non-Small Cell Lung Cancer: Proteomics Approach

Abstract

Background: Lung cancer is one of the major causes of death worldwide, with more than a million deaths a year. Despite advanced surgical techniques and combined therapies, lung cancer is still a disease with poor prognosis. According to available reports, the number of patients with lung cancer among Iranian men and women is increasing. In a study, 4,361 deaths from lung cancer have been recorded in Iran, which are 9.80% and 6.07% of all cancer deaths among men and women, respectively. Objectives: This study aimed at investigating the proteomes in patients with non-small cell lung cancer (NSCLC) and comparing them with those of the healthy individuals to detect protein markers for the diagnosis of the disease in the early stages. Methods: According to the sample size estimation, the tissue samples of 30 patients with NSCLC were compared with 30 healthy tissues. Proteomics and reverse transcriptase polymerase chain reaction (RT-PCR) methods were used. First, the tissue samples were collected under sterile conditions and then protein was extracted. Next, 2-dimensional electrophoresis and mass spectrometry were performed. Finally, with proteomic analysis in patients and healthy individuals, differences in the proteomic pattern of healthy and cancerous tissue were examined. Results: More than 40 differences were revealed in the proteomics pattern of the healthy and cancerous tissues, and 2 different spots were submitted for liquid chromatography-mass spectrometry (LC-MS/ MS). Then cytochrome b5 reductase 2 (CYB5R2) and fructose-1,6-bisphosphate1 were detected. It has been shown that these proteins down-regulated in cancer tissue compared to healthy tissue. It was also shown molecularly that the expression of fructose-1,6-bisphosphatase 1 messenger ribonucleic acid (mRNA) and cytochrome b5 reductase 2 messenger ribonucleic acid (mRNA) in the cancerous tissue was 0.8 and 0.64 times less than their expression in healthy tissues, respectively. Conclusions: The result of this study, which deals with tumor markers of NSCLC, can be considered as a screening diagnostic test for diagnosis of the disease in the early stages. This research could provide the basis for further research to identify the critical effects of these 2 molecules cytochrome b5 reductase 2 and fructose-1,6-bisphosphate on tissue carcinogenesis. It is recommended to do more thorough research.