Effect of epidermal growth factor receptor mutation on early-stage non-small cell lung cancer according to the 8th TNM classification.

Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T-cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. To comprehensively profile the TCR repertoire, results from high-throughput sequencing of samples from 93 Chinese patients with lung cancer were analyzed. We found that the TCR clonality of tissues was related to smoking, with higher clonality in patients who had quit smoking for less than 1 year. As expected, TCR clonality was correlated with stages: patients with stage IV disease showed higher clonality than others. The correlation between TCR repertoire and epidermal growth factor receptor (EGFR) status was also investigated. Patients with EGFR non-L858R mutations showed higher clonality and a lower Shannon index than other groups, including patients with EGFR L858R mutation and wild-type EGFR. Furthermore, we analyzed the TCR similarity metrics-that is, the TCR shared between postoperative peripheral blood and tissue of patients with non-distant metastasis of lung cancer. A similar trend was found, in which patients with EGFR L858R mutations had lower overlap index (OLI) and Morisita index (MOI) scores. Moreover, the OLI showed a positive correlation with several clinical characteristics, including the tumor mutational burden of tissues and the maximum somatic allele frequency of blood; OLI showed a negative correlation with the ratio of CD4+CD28+ in CD4+ cells and the ratio of CD8+CD28+ in CD8+ cells. In conclusion, TCR clonality and TCR similarity metrics correlated with clinical characteristics of patients with lung cancer. Differences in TCR clonality, Shannon index, and OLI across EGFR subtypes provide information to improve understanding about varied responses to immunotherapy in patients with different EGFR mutations.

/pdf/characteristics-of-t-cell-receptor-repertoire-and-1d0czmmeqz.pdf

Characteristics of T-Cell Receptor Repertoire and Correlation With EGFR Mutations in All Stages of Lung Cancer.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

https://www.mdpi.com/2075-4418/10/5/266/pdf

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients.

Effect of epidermal growth factor receptor gene mutation on the prognosis of pathological stage II-IIIA (8th edition TNM classification) primary lung cancer after curative surgery.

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 0.05). 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.

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

This study aimed to investigate the pure prognostic role of epidermal growth factor receptor (EGFR) mutation status and subtype in lung adenocarcinoma patients irrespective of therapy. We retrospectively enrolled 119 cases of completely resected pathological stage I lung adenocarcinoma patients who received no postoperative chemotherapy or tyrosine kinase inhibitors. EGFR gene mutations from 18 to 21 exons were tested for all the patients. Disease-free survival (DFS) and overall survival (OS) were compared between patients with different EGFR mutation status and subtype using Kaplan–Meier methods. EGFR mutations were detected in 54 (45.4%) patients including two common mutation subtypes: 32 in-frame deletion within exon 19 (19del) and 19 point mutation within exon 21 (L858R). The frequency of EGFR mutations was much greater for patients of non-smokers versus current or ever smokers (58.1 versus 24.4%, P = 0.000), and a little greater for females versus males (53.8 versus 35.2%, P = 0.042). The median follow-up duration was 43.5 months, and there were no differences on DFS (P = 0.461) and OS (P = 0.989) between patients with EGFR mutations and those without in univariate analysis. The patients harboring 19del mutation had a better DFS (P = 0.028) and OS (P = 0.001) than the patients harboring L858R mutation with significant statistical difference. This study suggests that there is no difference on survival between patients with EGFR mutations and those without, but the patients harboring EGFR 19del mutation have survival advantage compared to those harboring EGFR L858R mutation.

Prognostic implication of EGFR mutation status and subtype in resected lung adenocarcinoma patients irrespective of therapy.

Various edge low-frequency fluctuations with distinct characteristics exist in different detached divertor states. Three edge low-frequency fluctuations ( f< 10 kHz), namely low-frequency quasi-coherent fluctuation (LFCF), low-frequency broadband frequency fluctuation (LFBF), and low-n X-point mode (LNXM) on Experimental Advanced Superconducting Tokamak (EAST), are systematically assessed. The basic features of these fluctuations, such as spectral width, location, mode number, propagating direction, and particle transport capacities, are examined. LFCF occurs when the inner strike point is energy detached or nearly energy detached with Tet,inner∼ 8–15 eV ( Tet,inner is the electron temperature of the inner strike point), and a large electron temperature gap between the inner and outer strike points $?> with ΔTet> 25 eV ( ΔTet is the electron temperature gap between the inner and outer strike points) is essential for the occurrence of LFCF. By contrast, LFBF occurs when the inner strike point is energy detached with Tet,inner< 8 eV, while the outer strike point is nearly energy detached or attached. The ΔTet of LFBF is generally lower than that of LFCF, which is < 25 eV. LNXM is related only to the radiative divertor with impurity seeding and considered to be excited by the geodesic acoustic mode proposed in earlier work (Sun 2021 Nucl. Fusion 61 014002; Diallo 2020 28th IAEA Fusion Energy Conf.), or the coupling of impurity radiation condensation instability and drift waves proposed in a previous work (Ye 2021 Nucl. Fusion 61 116032). In addition, the possible physical mechanisms of LFBF and LFCF are proposed, with LFBF being the purely growing rippling mode and LFCF being the mode formed by the coupling of the rippling mode to the drift waves. Related research may be beneficial to better clarify the various low-frequency fluctuations that occur during different divertor states.

https://iopscience.iop.org/article/10.1088/1741-4326/acc4dd/pdf

Various edge low-frequency fluctuations during transition to a detached divertor in Experimental Advanced Superconducting Tokamak

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Prognostic implication of EGFR mutation status and subtype in resected lung adenocarcinoma patients irrespective of therapy.

Various edge low-frequency fluctuations during transition to a detached divertor in Experimental Advanced Superconducting Tokamak