The possibility of mutations of RAS signaling genes and/or TP53 in combination as a negative prognostic impact on pathological stage I non-small cell lung cancer.
TP53
RAS signaling genes
non-small cell lung cancer
pathological stage I
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
13
07
2023
received:
12
03
2023
accepted:
02
09
2023
medline:
23
10
2023
pubmed:
15
9
2023
entrez:
15
9
2023
Statut:
ppublish
Résumé
The recurrence rate of non-small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high-risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer-associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse-free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log-rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log-rank test, p = 0.10). Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.
Sections du résumé
BACKGROUND
The recurrence rate of non-small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high-risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis.
MATERIALS AND METHODS
A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer-associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA).
RESULTS
Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse-free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log-rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log-rank test, p = 0.10).
CONCLUSION
Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.
Identifiants
pubmed: 37712717
doi: 10.1002/cam4.6535
pmc: PMC10587933
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
KRAS protein, human
0
HRAS protein, human
EC 3.6.5.2
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Oncogene Protein p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19406-19413Informations de copyright
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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