Investigating Targeted Driver Mutations And Pd-L1 Expression For Improved Therapy Of Non-Small Cell Lung Cancer

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Date
2018-05-24
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Dalhousie University
Abstract
Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options to chemotherapy with very low response rate or other palliative managements. New therapies that target driver gene mutations (e.g. EGFR, ALK, BRAF), are being used to treat patients who have tumours with these mutations. In addition, a type of immunotherapy called immune checkpoint inhibitor is being used to treat lung cancer patients. For instance, patients with tumours that express PD-L1 may be responsive to anti PD-1/PD-L1 therapy. Thus, being able to identify the presence of driver mutations and PD-L1 in tumours will help patients to benefit from different therapies. A total of 851 cases of non-small cell lung cancer samples have been profiled for the presence of EGFR, KRAS, BRAF, and PIK3CA mutations by SNaPshot/sizing genotyping. Immunohistochemistry was used to identify the protein expression of ALK and PD-L1. Histological examination was performed to determine the pathological type, grade, and lymphatic/vascular invasion. Moreover, PD-L1 mRNA expression was quantified by RT-qPCR in a sub-group of the cohort to assess its correlation with PD-L1 protein level. Statistical analysis revealed correlations between the presence of the mutations, PD-L1 expression, and the pathological data. Specifically, it was determined that women had lung tumours with a significantly greater number of EGFR mutations than men. EGFR mutations were significantly linked to the absence of vascular invasion and PD-L1, and KRAS mutations do not associate with PD-L1 expression. Moreover, we found a positive correlation between mRNA levels of PD-L1 by RT-qPCR with PD-L1 expression by IHC. Together, these data provide insights into driver gene mutations and immune checkpoint status in relation to lung cancer subtypes and pathological characteristics and provide useful information for clinical implications.
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Lung cancer, Patients
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