carcinoma lung - major updates in biomarkers for early diagnosis

Authors:Anil Batta, KMDS Panag, Navneet Kaur
Int J Biol Med Res. 2012; 3(3): 1964 - 1971.  |  PDF File


Every third patient is suffering from of total cancer patints is enough INDICATOR to become a cause of woory for the humanity.. But hazy appearnace in the form of inflmmation restricts our attention.So this must be taken as horror sign and along with X-Ray chest the bronchoscopy should be a tool for early suspician thouh it gives unpleasant response.. Recently special protein biomarkers in exhaled air has been quite handy. However, the amount of data generated from studies first on resected tumours, then on early bronchial lesions and more recently on blood and sputum offer a wide field for investigation. The main difficulty lies in finding a reliable way to distinguish cancer from chronic inflammatory disease researchers have developed a laboratory method for reliably identifying biomarkers specific to lung cancer in special samples of exhaled air. Biomarkers are detected by means of special antibodies that recognize substances such as the protein VEGF. The patient must breathe into a piece of equipment for roughly 20 minutes. The exhaled breath condensate is then evaporated. This method elaborates stimulating the growtg of new blood vessels.But in the first outset method is elaborate and expensive. Along with protein bimarkers ,the antibody specially developed for diagnosis for ths procedure might be detected.This seems to act like special platform within reach to start trament on those lines. Genetic and epigenetic abnormalities in the genes involved in cell cycle, senescence, apoptosis, repair, differentiation and cell migration control may be detected on bronchial biopsies, on respiratory cells from the sputum and even in the circulating deoxyribonucleic acid (DNA). The key genes involved include those in the P53- retinoblastoma (Rb) pathways. The demonstration of hyperexpression or silencing of these genes needs different validated techniques: immunohistochemistry on biopsies or cytological preparations, molecular biology techniques for mutations, loss of heterozygosity and aberrant methylation abnormalities. Automation and miniaturisation of these techniques will allow early detection and may be widely applied once clinically validated. Despite the advances made in diagnosis and treatment in the last few decades, the prognosis oflung cancer is still very poor, with a 5-yr overall survival generally <10% in many countries. Lung cancer is detected by symptoms at a time when the local and moreover the metastasis extension hamper any hope of cure. Lung carcinogenesis is a multistep and multicentric process, characterised by the stepwise accumulation of genetic and molecular abnormalities after carcinogen exposure. carcinogenic process may randomly affect any site in the bronchial tree and concomitant lesions can be of different ages and might progress at different rates towards invasion. Molecular lesions occur in normal looking epithelium in the absence of dysplasia. As metaplasia in smokers displays genetic abnormalities, it can now be considered as a preneoplastic lesion. uncontrolled growth of clonal cells and an increased ability of these cells to migrate, characterises cancer progression, i.e. tumour growth and metastasis. The activation of oncogenes may be due to genetic modification: mutation, amplification, chromosomal rearrangement or epigenetic modification such as hyperexpression. Most high-grade lesions are now treated locally, which means that their natural history cannot be clearly understood. In the lung parenchyma, atypical alveolar dysplasia, considered as a preneoplastic lesion preceding bronchiolo-alveolar carcinoma, also exhibits genetic abnormality accumulation. Genetic modifications seem difficult to correct without a very well-targeted gene transfer. Whatever the mechanisms, the loss of expression or, on the contrary, the hyperexpression of a protein are the best methods to show the inactivation or the activation of a gene. All the methods of detection of malignant cells at (DNA), (RNA) or protein level may be applied on different samples obtained from the patient (blood, sputum, biopsies). However, to be used as a biomarker they need to fulfil different requirements. LOH can now be studied with miniaturised and automated techniques on microarray . This allows a wider study of chromosome loci and a decrease in artefacts, due to the preparation of the sample using small sequences such as the single nucleotide polymorphism.