The Association of EGFR Mutations with Stage at Diagnosis in Lung Adenocarcinomas

Cho, Jae-Young; Choi, Sun Mi; Lee, Jun Young; Lee, Chang Hoon; Lee, Sang Min; Yim, Jae Joon; Chung, Doo Hyun; Yoo, Chul Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

doi:10.1371/journal.pone.0166821

Cited by 8 publications

(10 citation statements)

References 34 publications

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“…Studies have suggested that EGFR mutation rates in patients with lung adenocarcinoma differ among countries and ethnicities, between sexes, and with smoking status ( 25 – 27 ). The overall mutation rate of EGFR in Chinese patients with lung adenocarcinoma in the present study was 50.7%, which is consistent with previous reports ( 6 , 25 – 27 ). The mutation rate in female patients was significantly higher than that of male patients (P<0.001) while the mutation rate in smokers was low compared with non-smokers (P=0.003), which was also consistent with previous reports ( 25 , 26 , 28 ).…”

Section: Discussionsupporting

confidence: 93%

“…Lung adenocarcinoma is the most common subtype of NSCLC, with a high recurrence rate and short survival time ( 4 ). According to previous research, oncogenes serve an important role in the occurrence and development of lung adenocarcinomas, and may be potential therapeutic targets ( 4 – 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) is an important driving gene in lung adenocarcinoma, and it has been reported that EGFR mutations are more common in Asian patients, non-smokers and females ( 6 ). Previous studies have demonstrated that mutation of EGFR is a positive predictor of prognosis for patients with lung adenocarcinoma ( 7 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma

et al. 2018

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Epidermal growth factor receptor (EGFR) is an important gene in the development of lung adenocarcinoma. However, there is controversy regarding the association between EGFR mutations and survival time of patients with lung adenocarcinoma. In the present study, tissue specimens and clinical data were collected from 219 patients with lung adenocarcinoma who had not undergone prior radiotherapy or chemotherapy. EGFR mutations were detected using a fluorescence polymerase chain reaction method, and the association between EGFR mutations and clinicopathological characteristics was analyzed. Overall survival (OS) curves were constructed using the Kaplan-Meier method and the influence of clinicopathological characteristics on OS was analyzed using the Cox regression model. The EGFR mutation rate was 50.7%, and the most common mutations were the L858R substitution mutation in exon 21 (L858R; 54.9%) and the deletion mutation in exon 19 (19-Del; 36%). The presence of EGFR mutations varied significantly with sex, smoking history, T stage, vascular invasion and adenocarcinoma subtypes (P<0.05). The survival time was significantly longer for female, young (<60 years-old), non-smokers or patients exhibiting EGFR mutations (G719X, 19-Del, L858R and L861Q). The survival time was also significantly longer for patients with a 19-Del mutation, early stage tumors, tyrosine kinase inhibitors targeted therapy-treated patients, for those not exhibiting nerve or vascular invasion, and for those without disease recurrence (P<0.05). Multivariate analysis revealed that tumor pathological Tumor-Node-Metastasis (pTNM) stage, nerve invasion, vascular invasion, EGFR mutation and the 19-Del mutation were independent predictors (P<0.05). Therefore, tumor pTNM stage, nerve invasion, vascular invasion and EGFR mutation status, particularly that of 19-Del, were independent prognostic factors for patients with lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma

et al. 2018

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“…Previously, in studies of other cancers, GMFs have been found to vary in different stages of cancer. [3637383940] However, to the best of the author's knowledge, this is the first study demonstrating GMF variation in different stages of endometrial carcinoma.…”

Section: Discussionmentioning

confidence: 89%

Mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades: An analytical study

Althubiti

2019

Saudi J Med Med Sci

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Background:Endometrial carcinoma is a predominant health problem for women worldwide. However, there is a lack of data on genetic mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades.Objective:The objective of this study is to provide data regarding mutation frequencies in endometrial cancer patients of different ethnic groups and tumor grades by analyzing large-scale cancer genomic datasets of a database.Materials and Methods:The following databases of cBioPortal were explored for possible mutation frequency variations in endometrial cancer patients: the Uterine Corpus Endometrial Carcinoma (TCGA, PanCancer Atlas) database for ethnicity-based studies; the Uterine Corpus Endometrial Carcinoma (TCGA, Nature 2013) database for tumor grade-based study; and GDC Data Portal database for calculating survival rates using the Kaplan–Meier method.Results:PTEN mutation frequency was almost identical in all ethnic groups studied (White, Black/African American, Asian, Native Hawaiian or other Pacific Islander, and American Indian or Asian Native). PIK3CA and ARID1A mutation frequencies were higher in White and Asian patients compared with other ethnicities; TP53 and FAT1 mutation frequencies were higher in Black/African Americans; and CTNNB1 and RYR2 mutation frequencies were higher Native Hawaiians or Asian Natives. TTN mutation frequency was lower in Asian patients. With regards to mutation frequencies at different tumor stages, in all genes, >50% of the mutations occurred during the first stage, except in TP53 and POLQ. In terms of prognosis in endometrial cancer considering the 10 most frequently mutated genes, PIK3CA and ARID1A mutations were correlated with good prognosis, whereas TP53 and PIK3R1 mutations were correlated with poor prognosis; mutations in all other genes did not show significant differences.Conclusion:This study revealed a new mutation frequency profile for different ethnicities and tumor grades in endometrial cancer patients. However, because this is a retrospective study, future prospective studies should be conducted including large sample sizes and more controlled measurements.

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“…Activating EGFR mutations are involved in the pathogenesis of a significant subset of lung adenocarcinomas 11 . The frequency of EGFR mutations in lung adenocarcinomas worldwide varies (from 8–13% in European populations to 27–60% Asian populations) according to ethnicity, gender, and tobacco exposure 12,13 . EGFR gene has emerged as a critical therapeutic target and EGFR mutations status has successfully guided clinical management 14 .…”

Section: Introductionmentioning

confidence: 99%

Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations

Leal

Paula

Marchi

et al. 2019

Sci Rep

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Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients’ genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR -exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.

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The Association of EGFR Mutations with Stage at Diagnosis in Lung Adenocarcinomas

Cited by 8 publications

References 34 publications

Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma

Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma

Mutation frequencies in endometrial cancer patients of different ethnicities and tumor grades: An analytical study

Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations

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