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| Item Type: | Article |
|---|---|
| Title: | TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading |
| Creators Name: | Schallenberg, S., Dernbach, G., Dragomir, M.P., Schlachtenberger, G., Boschung, K., Friedrich, C., Standvoss, K., Ruff, L., Anders, P., Grohé, C., Randerath, W., Merkelbach-Bruse, S., Quaas, A., Heldwein, M., Keilholz, U., Hekmat, J.K., Rückert, C., Büttner, R., Horst, D., Klauschen, F. and Frost, N. |
| Abstract: | OBJECTIVES: 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. RESULTS: Univariate analysis revealed TTF-1 positivity associated with significantly longer disease-free survival (DFS) (median log HR -0.83; p = 0.018). Higher tumor grade showed a non-significant association with shorter DFS (median log HR 0.30; p = 0,62 for G1 to G2 and 0.68; p = 0,34 for G2 to G3). In multivariate analysis, TTF-1 positivity resulted in a significantly longer DFS (median log HR -0.65; p = 0.05) independent of all other parameters, including grading. Adjusting for potential confounders as indicated by the causal graph confirmed the superiority of TTF-1 over tumor grading in prognostics power. CONCLUSIONS: TTF-1 status predicts relapse and survival in LUAD independently of tumor grading. The prognostic power of tumor grading is limited to TTF-1-positive patients, and the effect size of TTF-1 surpasses that of tumor grading. We recommend including TTF1 status as a prognostic factor in the diagnostic guidelines of LUAD. |
| Keywords: | TTF-1, LUAD, Tumor Grade, Prognosis, Prognostic Factor, Bayesian Network, Causal Inference |
| Source: | European Journal of Cancer |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier |
| Volume: | 197 |
| Page Range: | 113474 |
| Date: | January 2024 |
| Official Publication: | https://doi.org/10.1016/j.ejca.2023.113474 |
| PubMed: | View item in PubMed |
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