Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer
Abstract
Background: Mutations in Kelch‐like ECH‐associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease‐free interval using resected primary NSCLC tissue. Methods: We retrospectively analyzed the tumors from 79 patients with completely resected pathological Stage I–II NSCLC for the presence of Keap1 gene mutations and examined the prognosis of the patients. Results: Keap1 gene mutations were detected in four patients (5.1%). The postoperative 5‐year survival rate for patients with Keap1 mutations was significantly lower than those without a mutation (25% vs. 76%, P = 0.038). The postoperative 5‐year disease‐free survival rate for patients with a mutant Keap1 tumor was slightly lower than for patients with Keap1 wild‐type tumors (25% vs. 66%, P = 0.057). Conclusions: Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease‐free survival rates in pathological Stage I–II NSCLC. J. Surg. Oncol. 2010; 101:500–506. © 2010 Wiley‐Liss, Inc.
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Some somatic mutations give rise to hyperactive Nrf2, which causes enhanced antioxidant capacity and confers protection of cancer cells from ROS and cancer therapy, leading to cancer cell growth and proliferation, cancer progression, and cancer therapy resistance.
“Some somatic mutations give rise to hyperactive Nrf2, which causes enhanced antioxidant capacity and confers protection of cancer cells from ROS and cancer therapy, thereby leading to cancer cell growth and proliferation, cancer progression, and cancer therapy resistance (e.g., chemoresistance) (Figure 8) [161,162,163,164,165,166,167,168,169,170,171].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [169]
Aberrant Nrf2 expression and poor prognosis have been revealed in a wide range of cancers, including lung, esophageal, breast, bladder, liver, prostate, and colorectal carcinomas.
“numerous studies have revealed aberrant Nrf2 expression and poor prognosis in a wide range of cancers, including, among others, lung, esophageal, breast, bladder, liver, prostate, and colorectal carcinomas [161,162,169,170,171,173,174]”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [169]
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Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy
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Nrf2 Mutation/Activation Is Dispensable for the Development of Chemically Induced Mouse HCC
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Oxidative stress in the pathogenesis and prognosis of ovarian cancer
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The Keap1-Nrf2 Signaling Pathway in Lung Cancer
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Optical imaging of treatment-naïve human NSCLC reveals changes associated with metastatic recurrencePreprint
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Ciblage thérapeutique de la réponse au stress cellulaire dans l'ostéosarcome
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- Authors
- Takahashi, T., Sonobe, M., Menju, T., Nakayama, E., Mino, N., Iwakiri, S., Nagai, S., Sato, K., Miyahara, R., Okubo, K., Hirata, T., Date, H., & Wada, H.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Sonobe, Makoto
- Venue
- Journal of Surgical Oncology
- Publisher
- Wiley
- Published
- 2010-03-08
- Volume
- 101
- Issue
- 6
- Pages
- 500-506
- ISSN
- 0022-4790 (ISSN-L)
- 1096-9098
- OpenAlex
- W2092389969
- Cited by
- 78
- References
- 29
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 8
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Surgical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- Keap1, genetic mutations, non-small cell lung cancer, prognostic factors, resected lung cancer, postoperative survival, disease-free survival, early-stage lung cancer, chemoresistance
- MeSH terms
- Aged, Aged, 80 and over, Base Sequence, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prognosis, Retrospective Studies, Smoking, Survival Rate, DNA, Complementary, Disease-Free Survival
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