Abstract

Objectives: This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for EGFR mutation status in advanced NSLCL. Methods: A systematic searching of databases, including PubMed, EMBASE, Cochrane Library, and Google Scholar, was performed to identify studies assessing the correlation of TTF-1 expression with EGFR mutations. From 17 studies, 9764 patients were included in the combined analysis of odds ratio (OR) for the correlation between TTF-1 expression and EGFR mutations. Results: Compared with NSCLCs showing negative TTF-1 expression, tumors harboring TTF-1 overexpression showed a significantly higher rate of EGFR mutations (OR = 5.19, 95% confidence interval: 3.60–7.47, p < 0.00001). This correlation was observed in both subgroups of East Asian (OR = 4.33, 95% CI: 3.46–5.41, p < 0.00001) and European patients (OR = 4.64, 95% CI: 1.41–15.28, p < 0.01). In addition, TTF-1 expression was significantly associated with EGFR mutations in exon 19 (OR = 4.63, 95% CI: 2.89–7.41, p < 0.00001) as well as exon 21 (OR = 3.16, 95% CI: 1.04–9.60, p = 0.04). Conclusions: This meta-analysis demonstrates a significant correlation between TTF-1 expression and EGFR mutations in patients with NSCLC. The status of TTF-1 expression may be a biomarker to guide anticancer treatment in patients with NSCLC and unknown EGFR mutation status.

Highlights

  • Lung cancer is the second most common malignancy in both genders worldwide [1]

  • tyrosine kinase inhibitors (TKIs) are small molecular agents targeting epidermal growth factor receptor (EGFR) mutations that have revolutionized the treatment of non-small-cell lung cancer (NSCLC), leading to improved survival in patients with advanced or metastatic EGFR-mutant tumor [6,7]

  • It is essential to screen for EGFR mutations before introducing anticancer treatment for patients with advanced NSCLC

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Summary

Introduction

Lung cancer is the second most common malignancy in both genders worldwide [1] It still remains the leading cause of cancer-associated deaths [1,2], systemic chemotherapy or immune checkpoint inhibitors can significantly improve prognosis for patients with advanced non-small-cell lung cancer (NSCLC) [3,4,5]. High TTF-1 expression by immunohistochemistry (IHC) has been observed in 70–90% of primary lung adenocarcinomas (ADCs), while almost all squamous cell carcinomas are negative for TTF-1 IHC. It has been considered a specific marker of ADCs of the lung.

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