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TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading

Simon Schallenberg
Gabriel Dernbach
Mihnea P. Dragomir
Georg Schlachtenberger
Kyrill Boschung
Corinna Friedrich
Kai Standvoss
Lukas Ruff
Philipp Anders
Christian Grohé
Winfried Randerath
Sabine Merkelbach-Bruse
Alexander Quaas
Matthias Heldwein
Ulrich Keilholz
Jens Khosro Hekmat
Carsten Rückert
Reinhard Büttner
David Horst
Frederick Klauschen
Nikolaj Frost

December 14, 2023

Thyroid transcription factor 1 (TTF-1) is a well-established independent prognostic factor in lung adenocarcinoma (LUAD), irrespective of stage. This study aims to determine if TTF-1′s prognostic impact is solely based on histomorphological differentiation (tumor grading) or if it independently relates to a biologically more aggressive phenotype. We analyzed a large bi-centric LUAD cohort to accurately assess TTF-1′s prognostic value in relation to tumor grade.

Patients and methods
We studied 447 patients with resected LUAD from major German lung cancer centers (Berlin and Cologne), correlating TTF-1 status and grading with clinical, pathologic, and molecular data, alongside patient outcomes. TTF-1′s impact was evaluated through univariate and multivariate Cox regression. Causal graph analysis was used to identify and account for potential confounders, improving the statistical estimation of TTF-1′s predictive power for clinical outcomes.