Role of liquid biopsy in non small cell lung cancer

Abstract

Lung cancer is the leading cause of morbidity and mortality worldwide. It is usually diagnosed in advance stage. miRNA present in serum and pleural fluid can be studied for early diagnosis of lung cancer. Present study was carried out to evaluate whether miRNA can be used as biomarkers in diagnosis of non small cell lung cancer. The study was intended to find the non-invasive tumour biomarkers for presence of lung malignancy with the intent of instituting early diagnosis to reduce lung cancer related mortality. The aim of the study was to evaluate circulating microRNA expression in adenocarcinoma and squamous cell carcinoma lung in comparison with age and sex matched healthy controls. The expression of these miRNA was correlated with histopathology and/or immunohistochemistry. The circulating miRNA expression in age and sex matched non-smoking healthy controls was also noted. It was a Prospective observational study in which 50 cases of non small cell lung cancer was included. 50 healthy non smoker volunteers (control group, well adjusted to the patients according to the age and sex) were also included in the study. About 5 ml of serum and wherever possible pleural fluid was collected in the sterile container. The sample was allowed to stand at room temperature for one hour, and then samples were centrifuged at 1300g for ten minutes at room temperature.RNA was extracted using miRNeasy mini kit (Cat no. 217004) and quantative PCR was done. The patients age, sex, histopathological results, clinical staging, immunohistochemistry, presence of pleural effusion. Expression of mi RNA (miRNA 21, miRNA 17-92 cluster, miRNA 221/222, miRNA Let- 7, miRNA 34 and miRNA 200) were studied. Out of 50 patients of suspected lung cancer 17 were females (34%) and 33 (66%) were males. Mean age of presentation was 63.26 years. 37 patients gave history of smoking (74%) while 13 patients were non Smokers (26%). 29 patients (58%) showed histomorphological features suggestive of adenocarcinoma whereas 21 patients (42%) showed histomorphological features of squamous cell carcinoma. EGFR mutation was seen in 10 patients (34%). Pleural effusion was present in 20 cases.Statistically significant correlation was found between the expression of miRNA in healthy controls and in lung cancer patients. All the tested miRNAs were significantly correlated with the corresponding expression in the healthy control. As compared to healthy controls that let-7, miR-34 and miR-200 were downregulated in lung cancer patients whereas miRNA-221, miRNA 17-92, miRNA-21 were upregulated in lung cancer patients. miR 34, miR 200 and let 7 was detected in healthy controls also. No statically significant correlation of miRNA with age, sex, smoking, histopathological type, grade of tumor, stage of disease, EGFR mutation and IHC was found. Stastically significant correlation was found between miRNA 200 and pleural effusion patients. Present study concludes that miRNA can be a potential biomarker for diagnosing lung cancer. To date, there is convincing evidence supporting the potential role of miRNAs as biomarkers for lung cancer diagnosis and prognosis. However, further research is required in this aspect.