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Despite several advances in cancer diagnosis and treatment, the prognosis of advanced lung cancer remains poor. In previous studies, patient-related factors such as performance, age, and female sex were identified as independent prognostic indicators of lung cancer stage [1]. Although there are many studies on prognostic biomarkers, most of them did not adjust for previous prognostic factors. Similar to epidermal growth factor receptor (EGFR) mutations, some specific driving mutations for target treatment are not only predictive factors for outcomes but also play a prognostic role [2]. Targeted therapy is a standard treatment modality in lung adenocarcinoma even in elderly patients or those with a poor performance status [3]. As such, more objective independent prognostic biomarkers are needed in clinical practice and in studies on lung cancer; this is particularly true for lung adenocarcinoma because of its increasing incidence worldwide [4].
Thyroid transcription factor (TTF)-1 is a tissue-specific transcription factor that has a homeodomain protein fold and regulates the expression of select genes in the thyroid and lung for embryonic development and differentiation [5]. The importance of TTF-1 extends into adulthood as it plays a critical role in maintaining the normal function of terminal respiratory unit cells by controlling surfactant proteins [6]. TTF-1 is a lineage marker and has been used as a diagnostic marker for lung adenocarcinoma and small cell carcinoma [7]. A subsequent study showed that TTF-1 overexpression was a favorable prognostic marker among patients with lung adenocarcinoma [8]. Anagnostou et al. showed that TTF-1 expression positively impacted the survival of stage I lung adenocarcinoma patients [9]. Although several studies also demonstrated similar results in advanced stage lung adenocarcinoma, there were some limitations such as small sample sizes or an uncontrolled driving mutation status. Chung et al. showed that TTF-1 was an independent prognostic factor among patients treated with EGFR tyrosine kinase inhibitors (TKI). However, they did not control for treatment lines, and EGFR-TKI treatment was not based on the EGFR mutation status [10]. The prognostic significance of TTF-1 among patients with wild-type EGFR adenocarcinoma has not been studied adequately. Moreover, research on the prognosis of patients with TTF-1-negative, EGFR-positive adenocarcinoma is also limited. The good prognostic capability of TTF-1 expression might be due to EGFR-sensitizing mutations as demonstrated by the positive correlation between TTF-1 expression and EGFR mutations [10, 11]. The purpose of this study was to explore the prognostic impact of TTF-1 expression based on the EGFR-sensitizing mutation status in lung adenocarcinoma patients.
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