Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non–Small Cell Lung Cancer: Brief Report

Owada-Ozaki, Yuki; Muto, Satoshi; Takagi, Hironori; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Yamaura, Takumi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, T.; Ohsugi, Jun; Hoshino, Mika; Shio, Yutaka; Nanamiya, Hideaki; Imai, Jun‐ichi; Isogai, Takao; Watanabe, Shinya; Suzuki, Hiroyuki

doi:10.1016/j.jtho.2018.04.003

Cited by 122 publications

(118 citation statements)

References 9 publications

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“…First, our WGS cohort was based on patients with HCC who had early tumor recurrence, and higher mutational burden has been associated with poor prognosis in several types of cancer. [23][24][25][26] Second, we identified 5 prominent mutational signatures; Signature A (aristolochic acid) and Signature C (aflatoxin) were the dominant signatures in 34.7% (17/49) of the patients, which was different from other HCC cohort studies. [5][6][7] Exposures to aristolochic acid or aflatoxin are important environmental risk factors for HCC development, especially in China, and are known to contribute to hypermutation in cancer.…”

Section: Discussioncontrasting

confidence: 66%

Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence

Zhou

et al. 2019

Journal of Hepatology

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Section: Discussioncontrasting

confidence: 66%

Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence

Zhou

et al. 2019

Journal of Hepatology

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“…In addition, TMB and PD-L1 expression may predict the response to ICI and clinical benefit in some studies, [48][49][50][51][52] but the positive results are not observed in several other studies. [53][54][55][56] In our study, we did not find significant differences in TMB and PD-L1 expression between the 11-IRG signature high-risk group and the low-risk group. The relevance of the signature to ICI response is not yet fully understood and further research is needed.…”

Section: Prediction Of Ici Responsecontrasting

confidence: 62%

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors

et al. 2019

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2019) Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors, OncoImmunology, 8:12, e1659094, ABSTRACT Cervical cancer (CC) is a leading cause of cancer-related death in women. Limited studies have investigated whether immune-related genes (IRGs) or tumor immune microenvironment (TIME) could be indicators for CC prognoses. The aim of this study was to develop an improved prognostic signature for CC based on IRGs or TIME to predict survival and response to immune checkpoint inhibitors (ICIs). A prognostic signature was constructed using bioinformatics method and its predictive capability was validated. The mechanisms underlying the signature's predictive capability were explored with CIBERSORT algorithm and mutation analysis. Immunophenoscore (IPS) is validated for ICIs response, and was therefore explored in relation to the signature. A prognostic signature based on 11 IRGs was developed. A multivariate analysis revealed that the 11-IRG signature was an independent prognostic factor for overall survival (OS) and progression-free interval in CC patients. In the 11-IRG signature highrisk group, CD8 T cells and resting mast cells, which are found to associate with better OS in our study, were lower; activated mast cells, associated with poorer OS, were higher, compared with the low-risk group. An IPS analysis suggested that the 11-IRG signature low-risk group, which possessed a higher IPS, represented a more immunogenic phenotype that was more inclined to respond to ICIs. In short, an 11-IRG prognostic signature for predicting CC patients' survival and response to ICIs was firmly established. The predictive capability of this model in CC requires further testing with the goal of better prognostic stratification and treatment management. ARTICLE HISTORY

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“…TMB is a measure of the number of somatic mutations within a tumor, and is defined as the total number of somatic mutations per coding area of a tumor genome . High TMB was associated with worse OS of patients with resected NSCLCs, and was also negatively associated with survival in patients with metastatic EGFR ‐mutant lung cancers treated with EGFR TKIs . Thus, it is possible that TMB was a hidden confounder in the current study with respect to the relationship between the prognostic effect of EGFR mutation and patient age.…”

Section: Discussionmentioning

confidence: 86%

The prognostic implications of EGFR mutation and ALK rearrangement for the long‐term outcomes of patients with resected lung adenocarcinomas

et al. 2019

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Background To investigate the prognostic impact of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement for the overall survival (OS) of patients with surgically treated lung adenocarcinomas. Methods A total of 689 patients with stage I–III lung adenocarcinomas (male:female = 334:355; median age, 64 years) underwent complete surgical resection between 2007 and 2013. The prognostic impact of EGFR mutation and ALK rearrangement on OS was analyzed using Cox regression analysis. Certain clinicopathological prognostic factors (i.e., age, sex, smoking status, nodule type, solid portion size, pathologic stage, adenocarcinoma subtype, and history of adjuvant chemotherapy) were included for adjustments of the hazard ratio (HR). Results EGFR mutation was observed in 438 patients (64%) and ALK rearrangement was seen in 28 patients (4%). Multivariable‐adjusted Cox regression demonstrated that the prognostic effect of EGFR mutation on OS differed by age (HR, exp.[−5.199 + 0.064*age]). The adjusted HR for EGFR mutation was 0.14 (95% CI: 0.05–0.36; P < 0.001) at 50 years, 0.26 (95% CI: 0.15–0.46; P < 0.001) at 60 years, and 0.50 (95% CI: 0.31–0.81; P = 0.005) at 70 years. However, the effect of ALK rearrangement on OS was without statistical significance (P > 0.05). Conclusions EGFR mutation was independently prognostic of the long‐term outcomes of patients with surgically treated lung adenocarcinomas. A more favorable prognostic effect was seen in younger than in older patients. ALK rearrangement was not associated with OS.

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Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non–Small Cell Lung Cancer: Brief Report

Abstract: High TMB in NSCLC is a poor prognostic factor. If high TMB is a predictor of the efficacy of immune checkpoint inhibitors, postoperative adjuvant therapy with immune checkpoint inhibitors may contribute to improvement of recurrence and OS.

Cited by 122 publications

References 9 publications

Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence

Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence

Identification of a prognostic immune signature for cervical cancer to predict survival and response to immune checkpoint inhibitors

The prognostic implications of EGFR mutation and ALK rearrangement for the long‐term outcomes of patients with resected lung adenocarcinomas

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