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

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Zahra Najafi ◽  
Abdolreza Mohamadnia ◽  
Rahim Ahmadi ◽  
Minoo Mahmoodi ◽  
Naghmeh Bahrami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cytochrome B5 ◽  
Small Cell ◽  
Healthy Individuals ◽  
Small Cell Lung ◽  
Tissue Samples ◽  
Messenger Ribonucleic Acid ◽  
Cytochrome B5 Reductase ◽  
Fructose 1,6 Bisphosphatase ◽  
Cytochrome B5 Reductase 2

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.

scholarly journals miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer

2020 ◽  
Vol 117 (8) ◽  
pp. 4347-4357 ◽  
Author(s):  
Guang Liang ◽  
Wei Meng ◽  
Xiangjie Huang ◽  
Wangyu Zhu ◽  
Changtian Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Rna Binding ◽  
Nsclc Patient ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Samples ◽  
Underlying Mechanisms

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

scholarly journals Does a routine post brush bronchial wash increase the yield in diagnosis of lung cancer?

2017 ◽  
Vol 5 (7) ◽  
pp. 2878 ◽  
Author(s):  
Mathan Raj S. ◽  
Sowmiya Murali
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Fiberoptic Bronchoscopy ◽  
Small Cell ◽  
Fibreoptic Bronchoscopy ◽  
Small Cell Lung ◽  
Brush Cytology ◽  
Tissue Samples ◽  
Bronchial Wash

Background: Lung cancer is the most common cause of cancer-related death in both men and women. 80% of the lung cancers are non-small cell lung cancer (NSCLC) and 20% are small cell lung cancer (SCLC). Flexible fiberoptic bronchoscopy is commonly used for diagnostic and staging purposes. Endoscopically visible abnormalities are approached with traditional biopsy forceps, brushings, and washings. Objectives were to assess the yield of bronchial washings, brush cytology and to compare the yield of pre and post brush bronchial washings.Methods: Patients with suspicion of lung cancer will be subjected to bronchoscopy using flexible fibreoptic bronchoscopy. Multiple procedures performed for the retrieval of tissue samples will include bronchial washings (pre and post brushing), bronchial brushing and endobronchial biopsy.Results: A total of 57 cases were included in the study with 40 (70.2%) males and 17 females (29.8%). The yield of pre-brush bronchial washings, post brush bronchial washings and bronchial brushings were 31.6% (18 of 57), 31.6% (18 of 57) and 61.4% (35 of 57) respectively. Biopsy was positive for malignancy in 11 of 19 (58.2%) cases. Adenocarcinoma was the commonest type seen in 32 (56.1%) patients. Of the 27 cases with endobronchial growth 11 were adenocarcinoma (40.7%).Conclusions: There was no difference between the yield of pre-brush washing and post brush washing. The yield of brush cytology was significantly more than the yield of bronchial washings. There is an increase in the yield after adding both pre and post brush bronchial wash. 

scholarly journals MLPA-analysis of TP53 gene in patients with small-cell lung cancer

2020 ◽  
pp. 83-85
Author(s):  
Г.Ф. Гималова ◽  
З.С. Абдуллин ◽  
Э.К. Хуснутдинова
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Structural Changes ◽  
Malignant Tumors ◽  
Tp53 Gene ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Samples ◽  
The Republic

Мелкоклеточный рак легкого (МРЛ) составляет около 15-20% всех случаев РЛ и относится к наиболее злокачественно текущим опухолям. В более чем 90 % случаев МРЛ выявляются мутации гена TP53. Целью нашего исследования являлся анализ структурных изменений хромосомной области 17p13 у больных МРЛ из Республики Башкортостан. Материалом исследования служили 70 образцов тканей легких больных МРЛ. Методом исследования являлся MLPA-анализ. Делеции и/или дупликации в кодирующих областях гена TP53 выявлены в 40% образцов, в т.ч. дупликации первого (23% образцов) и делеции 4-6-го и 11-го экзонов гена TP53 (17% образцов). Кроме того, в четырех образцах выявлена мутация c.1100delC гена CHEK2. Small cell lung cancer (SCLC) accounts for about 15-20% of all lung cancer cases and is one of the most malignant tumors. In more than 90% of cases of SCLC, mutations of the TP53 gene are detected. The aim of our study was to analyze the structural changes in the 17p13 chromosomal region in patients with SCLC from the Republic of Bashkortostan. We used 70 lung tissue samples from patients with SCLC. The study was conducted using MLPA. Deletions and/or duplications in the coding regions of the TP53 gene were detected in 40% of the samples, including duplications of the first exon (23% of the samples) and deletions of the 4-6th and 11th exons of the TP53 gene (17% of the samples). Besides, the CHEK2 c.1100delC mutation was detected in four samples.

Identifying genomic alterations in small cell lung cancer using the liquid biopsy of bronchial washing fluid.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21098-e21098
Author(s):  
Jinfang Zhai ◽  
Songyan Han ◽  
Qinxiang Guo ◽  
Binbin Shan ◽  
Jing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Small Cell ◽  
Plasma Samples ◽  
Small Cell Lung ◽  
Tissue Samples ◽  
Bronchial Washing ◽  
Treatment Naïve

e21098 Background: With the rapid development of cancer genomics, the precision medicine of small cell lung cancer (SCLC) is emerging. However, there are limitations to the clinical use of tumor tissue and peripheral blood biopsies. The main purpose of this study was to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one SCLC patients diagnosed in 2019 were enrolled in this study. BWF (separated as supernatant and precipitate), treatment-naive plasma and tumor tissue samples were collected from all of patients and subjected to next-generation sequencing (NGS) using a 1021-gene panel. The concordance rates of genomic profiling using NGS in these four types of samples were evaluated. Results: Of these 21 patients, 20 BWF supernatant (BWFs) samples, 21 BWF precipitate (BWFp) samples, 21 tumor tissue samples and 20 plasma samples were successfully tested. The detectability of somatic mutations was 100% for BWFs, BWFp and tumor tissues, and only one plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp and plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, of which 189 (92.6%), 175 (85.5%) and 163 (79.9%) alterations were detected in the matched BWFs, BWFp and plasma samples, respectively. Moreover, tumor mutation burden (TMB) was also calculated. Compared with the proportion of TMB-H samples in tissue samples counting 61.9% (13/21), 60% (12/20) of BWFs samples and 52.38 % (11/21) of BWFp samples were TMB-H (defined as more than or equal to 9 mutations per megabase), which was a molecular biomarker that can be used in immunotherapy efficacy prediction. The TMBs of BWFs, BWFp and treatment-naive plasma samples all had strong correlation with that of tissue samples. The TMB of BWFs had the strongest correlation (Pearson r = 0.9512, p < 0.0001), and the TMB of treatment-naive plasma had relatively lower correlation (Pearson r = 0.8782, p < 0.0001) compared with those of BWFs (Pearson r = 0.936, p < 0.0001) and BWFp (Pearson r = 0.8782, p < 0.0001). Conclusions: For SCLC patients, the liquid biopsy of BWF showed high potential to identify DNA alterations and calculate TMB grades, which suggested that genomic analysis of BWF liquid biopsy may have clinical value in predicting the effectiveness of targeted therapy and immunotherapy. It can be widely used in routine clinical practice.

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