Association of EGFR 1 Gene Alteration and their Association with Lung Adenocarcinoma Patients

Document Type : Research Articles

Authors

1 Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.

2 Department of Pathology and Forensic Medicine, Waist University, Iraq.

3 Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

4 Department of Pulmonary Medicine and Sleep Disorder All India Institute of Medical Sciences, New Delhi, India.

Abstract

Background: The epidermal growth factor receptor 1 (EGFR1) plays a significant role in cell proliferation and
development. Its regulation in humans is very critical and incompletely understood in Non small cell lung cancer
(NSCLC). Methods: 100 newly diagnosed NSCLC (lung adenocarcinoma) patients and 100 healthy controls were
included and allele specific (AS) polymerase chain reaction (PCR) was used to genotype and expression was analyzed
by quantitative real time PCR. Overall survival of patients was analyzed by Kaplan-Meier method and for prognostic
significance ROC curve was plotted. Results: A statistically significant difference (p<0.0001) in CC, AA and CA
genotypes distribution among patients and healthy controls was observed. Compared to the CC genotype as reference,
OR was 30.40 (95%CI 1.75- 524.9, p=0.0002) and 3.97 (95%CI 1.49-10.52, p=0.003) for the homozygous AA and
heterozygous CA genotypes respectively. Kaplan-Meier survival analysis was also performed to analyze the relationship
of EGFR1 (-191C/A) genotypes with progression free median survival of NSCLC patients and the difference was
found to be significantly (p=0.0002) associated with different genotypes. In the ROC curve with respect to TNM stage
at optimal cut-off value of 9.88 fold increase in EGFR1 mRNA expression, sensitivity and specificity were 92.9%,
83.3% respectively (AUC=0.95, p<0.0001). ROC curve w.r.t. distant metastases at optimal cut-off value of 13.5 fold
change EGFR1 mRNA expression, sensitivity and specificity were 68.2%, 71.4% respectively (AUC=0.81, p<0.0001).
In ROC curve w.r.t to presence/ absence of pleural effusion at optimal cut-off value of 14.8 fold change EGFR1
mRNA expression sensitivity and specificity were 66.7%, 68.2% respectively (AUC=0.71, p=0.009). Conclusions:
Study concluded EGFR1 promoter polymorphism could be a risk factor associated with disease and may be used as
prognostic marker for patients’ survival and predictor for disease worseness.

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