| Full text | |
| Author(s): Show less - |
Machado-Rugolo, J.
;
Baldavira, C. M.
;
Prieto, T. G.
;
Olivieri, E. H. R.
;
Fabro, A. T.
;
Rainho, C. A.
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Castelli, E. C.
;
Ribolla, P. E. M.
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Ab'Saber, A. M.
;
Takagaki, T.
;
Nagai, M. A.
;
Capelozzi, V. L.
Total Authors: 12
|
| Document type: | Journal article |
| Source: | Brazilian Journal of Medical and Biological Research; v. 56, p. 11-pg., 2023-01-01. |
| Abstract | |
TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early -stage resected EGFR-mutated NSCLC. (AU) | |
| FAPESP's process: | 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets |
| Grantee: | Vera Luiza Capelozzi |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/12151-0 - Evaluation of the protein expression of DLL-3 and ASCL-1 as a new perspective in biomarkers for the early diagnosis of small cell lung carcinomas |
| Grantee: | Tabatha Gutierrez Prieto Martins Rocha |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |