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Jing Zhang
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.91 - Analysis of P53 Lysine-Encoding Mutations Reveals a Relationship Between Codon 132 Mutations and EGFR Mutations in Lung Adenocarcinoma (ID 3660)
00:00 - 00:00 | Presenting Author(s): Jing Zhang
- Abstract
Introduction
P53 lysine changes lead to abnormalities of anti-cancer function, which caused by the mutations of corresponding codons in p53.Meanwhile, EGFR is an important driver gene of lung adenocarcinoma. In this study, we attempted to explore the relationship between EGFR mutations and mutations contributed to P53 lysine changes in lung adenocarcinoma.
Methods
79 patients with lung adenocarcinoma with p53 mutations which cause P53 lysine changes continuously included in Geneplus-Beijing institution (Beijing, China) from 2016.12 to 2018.12. Kruskal Wallis Rank Test and Fisher Exact were used. Generalized linear models and Generalized additive models were applied to evaluate the association between mutations at codon 132 and the EGFR mutations.
Results
The female group had a 1.83 times higher risk of EGFR mutations than the male group (OR=2.83, 95% CI 1.08=7.42, p=0.035,data was not shown), and the 132 mutation group had a 1.84 times higher risk of EGFR mutations than the group without 132 mutations (OR= 2.84, 95% CI, 1.06-7.62, p=0.038).After adjustment for age and gender, the 132 mutation group had a 1.41 times higher risk of EGFR mutations than the non-132 mutation group (OR=2.41; 95% CI=00.86-6.72, p = 0.093). After adjustment for age and analysis with the generalized additive models for gender, the 132 mutation group was shown to have a 2.04 times higher risk of EGFR mutations than the non-132 mutation group (OR=3.04, 95% CI=0.99-9.27, p=0.051). In addition, all 12 cases with K132R had EGFR mutations.(Table1).
Compared with the non-132 mutation group, the 132 mutation group had a 7.96 times higher risk of the T790M mutation (OR=8.96, 95% CI=1.81-44.29, p= 0.007), and the K132R group had a 3.33 times higher risk (OR=4.33, 95% CI=1.14-16.43, p=0.031)(Table2).
Table 1. Association of Codon 132 mutations or its’ subtypes with EGFR mutation Covariate Statistics OR (95%) P-value Adjust I (OR,95%CI, p) Adjust II (OR,95%CI, p) AdjustIII (OR,95%CI, p) Codon132 mutations No 45 (56.96%) Ref Ref Ref Ref Yes 34 (43.04%) 2.84 (1.06, 7.62) 0.038 2.57 (0.94, 7.04) 0.067 2.41 (0.86, 6.72) 0.093 3.04 (0.99, 9.27) 0.051 Subtype of codon132 mutations Non-132 45 (56.96%) Ref Ref Ref Ref 132R 12 (15.19%) _§ 0.992 _§ _§ _§ 132N 10 (12.66%) 1.31 (0.33, 5.29) 0.702 1.33 (0.32, 5.60) 0.694 0.91 (0.17, 4.75) 0.907 1.13 (0.17, 7.46) 0.901 132M 4 (5.06%) 2.62 (0.25, 27.19) 0.418 2.50 (0.23, 27.35) 0.453 2.47 (0.22, 28.07) 0.466 1.91 (0.15, 24.77) 0.621 132E 3 (3.80%) 1.75 (0.15, 20.71) 0.657 1.36 (0.11, 17.50) 0.812 1.36 (0.11, 17.52) 0.814 1.90 (0.09, 42.07) 0.686 132Q 3 (3.80%) 1.75 (0.15, 20.71) 0.657 0.94 (0.07, 12.20) 0.962 0.95 (0.07, 12.42) 0.967 0.91 (0.07, 12.72) 0.945 Other 132 mutations 2 (2.53%) 0.87 (0.05, 14.87) 0.926 0.78 (0.04, 14.59) 0.868 0.78 (0.04, 14.54) 0.866 0.67 (0.03, 12.75) 0.787 Table2. Univariate analysis for EGFR mutation subtypes. Statistics EGFR T790M
(OR,95%CI,p)EGFR 19DEL
(OR,95%CI,p)EGFR L858R
(OR,95%CI,p)Age 60.58 ± 12.12 1.00 (0.94, 1.05) 0.862 0.95 (0.91, 0.99)0.021 1.05 (1.00, 1.09) 0.049 Gender Male 42 (53.16%) Ref Ref Ref Female 37 (46.84%) 2.62 (0.72, 9.56) 0.144 0.50 (0.18, 1.36) 0.172 5.68 (1.93, 16.71) 0.002 Codon132 mutations No 45 (56.96%) Ref Ref Ref Yes 34 (43.04%) 8.96 (1.81, 44.29) 0.007 1.69 (0.63, 4.48) 0.295 1.50 (0.57, 3.94) 0.410 Subtype of codon 132 mutations Non-132 45 (56.96%) Ref Ref Ref 132R 12 (15.19%) 4.33 (1.14, 16.43) 0.031 0.92 (0.21, 3.96) 0.907 15.36 (2.48, 95.17) 0.003 132N 10 (12.66%) 0.34 (0.04, 3.02) 0.336 2.75 (0.67, 11.20) 0.158 5.38 (0.66, 43.91) 0.117 132M 4 (5.06%) 3.09 (0.39, 24.61) 0.286 0.92 (0.09, 9.69) 0.942 7.17 (0.50, 103.55) 0.148 132E 3 (3.80%) 1.55 (0.13, 18.73) 0.732 1.37 (0.11, 16.58) 0.802 _§ 132Q 3 (3.80%) 1.55 (0.13, 18.73) 0.732 1.37 (0.11, 16.58) 0.802 10.75 (0.66, 174.66) 0.095 Other mutations 2 (2.53%) _§ 2.75 (0.16, 47.52) 0.487 21.50 (0.96, 483.70) 0.053
Conclusion
Codon 132 mutations in P53 are associated with EGFR mutations and T790M, which is valuable for exploring the optimal strategy of EGFR-TKI treatment.
