Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Zhang, Xuelin; Ye, Tengfei; Li, Mingdong; Yan, Hongwang; Lin, Hui; Lu, Hongsheng; Qi, Zecheng; Sheng, Haihui; Chun-ya, HE

doi:10.3389/fonc.2022.836117

Cited by 4 publications

(3 citation statements)

References 76 publications

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“…Dai and Fu 62 constructed a prognostic model based on a panel of six necrosis‐related genes, including TNFRSF1A, to assess the prognosis of patients with LUAD. Zhang et al 63 demonstrated that high expression of TNFRSF1A was also associated with a poorer prognosis in patients with LUAD. Overexpression of RAC1 has been reported to be associated with EMT, which is able to promote tumor metastasis and progression in NSCLC through EMT 64 .…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation

Xu,

Ding,

Song

et al. 2024

The Journal of Gene Medicine

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BackgroundAberrant activation of the phosphatidlinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway has been shown to play an important role in lung adenocarcinoma (LUAD). The effect of KRAS mutations, one of the important signatures of LUAD, on the PI3K/AKT/mTOR pathway in LUAD remains unclear.MethodsThe Seurat package and principal component analysis were used for cell categorization of single‐cell RNA sequencing data of LUAD. The AUCell score was used to assess the activity of the PI3K/AKT/mTOR pathway. Meanwhile, using the gene expression profiles and mutation profiles in the The Cancer Genome Atlas dataset, LUAD patients were categorized into KRAS‐mutant (KRAS‐MT) and KRAS‐wild‐types (KRAS‐WT), and the corresponding enrichment scores were calculated using gene set enrichment analysis analysis. Finally, the subpopulation of cells with the highest pathway activity was identified, the copy number variation profile of this subpopulation was inscribed using the inferCNV package and the CMap database was utilized to make predictions for drugs targeting this subpopulation.ResultsThere is higher PI3K/AKT/mTOR pathway activity in LUAD epithelial cells with KRAS mutations, and high expression of KRAS, PIK3CA, AKT1 and PDPK1. In particular, we found significantly higher levels of pathway activity and associated gene expression in KRAS‐MT than in KRAS‐WT. We identified the highest pathway activity on a subpopulation of GRB2+ epithelial cells and the presence of amplified genes within its pathway. Finally, drugs were able to target GRB2+ epithelial cell subpopulations, such as wortmannin, palbociclib and angiogenesis inhibitor.ConclusionsThe present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.

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Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation

Xu,

Ding,

Song

et al. 2024

The Journal of Gene Medicine

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“…Moreover, the rs4819554 variant was significantly associated with worse progression-free survival and overall survival in patients with non-small cell lung cancer (NSCLC) [ 99 ]. Similarly, homozygosity for the AA genotype was linked to more significant deterioration of renal function [ 98 ] and increased primary graft dysfunction after lung transplantation [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Interleukin-17 Receptor A Gene Variants on Asthma Susceptibility and Clinical Manifestations in Children and Adolescents

Maher,

AbdAllah,

Ageeli

et al. 2024

Children

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Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has been implicated in tissue inflammation and autoimmune diseases. As no previous studies have uncovered the potential role of IL17 receptor A (RA) gene variants in asthma risk, we aimed to explore the association of four IL17RA SNPs (i.e., rs4819554A/G, rs879577C/T, rs41323645G/A, and rs4819555C/T) with asthma susceptibility/phenotype in our region. TaqMan allelic discrimination analysis was used to genotype 192 individuals. We found that the rs4819554 G/G genotype significantly reduced disease risk in the codominant (OR = 0.15, 95%CI = 0.05–0.45, p < 0.001), dominant (OR = 0.49, 95%CI = 0.26–0.93, p = 0.028), and recessive (OR = 0.18, 95%CI = 0.07–0.52, p < 0.001) models. Similarly, rs879577 showed reduced disease risk associated with the T allele across all genetic models. However, the A allele of rs41323645 was associated with increased disease risk in all models. The G/A and A/A genotypes have higher ORs of 2.47 (95%CI = 1.19–5.14) and 3.86 (95%CI = 1.62–9.18), respectively. Similar trends are observed in the dominant 2.89 (95%CI = 1.47–5.68, p = 0.002) and recessive 2.34 (95%CI = 1.10–4.98, p = 0.025) models. For the rs4819555 variant, although there was no significant association identified under any models, carriers of the rs4819554*A demonstrated an association with a positive family history of asthma (71.4% in carriers vs. 27% in non-carriers; p = 0.025) and the use of relievers for >2 weeks (52.2% of carriers vs. 28.8% of non-carriers; p = 0.047). Meanwhile, the rs4819555*C carriers displayed a significant divergence in the asthma phenotype, specifically atopic asthma (83.3% vs. 61.1%; p = 0.007), showed a higher prevalence of chest tightness (88.9% vs. 61.5%; p = 0.029), and were more likely to report comorbidities (57.7% vs. 16.7%, p = 0.003). The most frequent haplotype in the asthma group was ACAC, with a frequency of 22.87% vs. 1.36% in the controls (p < 0.001). In conclusion, the studied IL17RA variants could be essential in asthma susceptibility and phenotype in children and adolescents.

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“…It has been demonstrated that overexpression of YWHAE strengthens the invasiveness of breast cancer cells 22 , but no other studies have probed the impact of YWHAE on the outcome of LUAD. Preexisting research has shown that the overexpression of TNFRSF1A, ADM, ITGB1, PRMT1, and AREG is associated with an unfavorable prognosis in patients 23 - 27 . The model based on the above eight EIRGs showed that it has good predictive value, and similar results were obtained in the GEO external cohort.…”

Section: Discussionmentioning

confidence: 99%

Identification Of Endothelial Cell Immune-related Gene Signature for Lung Adenocarcinoma by Integrated Analysis of Single-cell and Bulk RNA Sequencing Data

Hu,

Wu,

Zhou

et al. 2024

J. Cancer

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Background:The role of endothelial cells in tumor progression is considerable, yet the effect of endothelial cell immune-related genes (EIRGs) is still unclear. This research aimed to scrutinize the prognostic value of EIRGs in lung adenocarcinoma (LUAD) and provide further insights into the abovementioned uncertainties. Methods: After single-cell RNA sequencing (scRNA-seq) samples were obtained from the Gene Expression Omnibus (GEO) database, they were integrated with bulk RNA sequencing data from The Cancer Genome Atlas (TCGA). Prognostic markers were determined and a prognostic model was developed. From this model, a nomogram was constructed. We analyzed the biological mechanism of the EIRGs in LUAD, including functional enrichment, tumor mutational burden (TMB), tumor microenvironment (TME) analyses and drug sensitivity. We validated the signature by validating the external cohort GSE31210 and RT-qPCR. Results: After analyzing the model constructed from eight EIRGs, we observed that high-risk group (HG) LUAD patients (a risk score exceeding 4.65) exhibited unfavorable outcomes according to Kaplan-Meier survival curves. This outcome was confirmed by GSE31210. The nomogram based on the model demonstrated significant predictive value. HG was influenced primarily by steroid hormone biosynthesis and ECM receptor interactions. The TMB in HGs was greater than that in the LG. Analysis of drug sensitivity revealed the direction for individualized treatment for both risk cohorts. Variations in the expression of EIRGs have been confirmed via RT-qPCR in several LUAD cell lines. Conclusions: The prognostic model and nomogram above are valuable for determining the survival rate and treatment options for LUAD patients.

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Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Cited by 4 publications

References 76 publications

Single‐cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation

Single‐cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation

Impact of Interleukin-17 Receptor A Gene Variants on Asthma Susceptibility and Clinical Manifestations in Children and Adolescents

Identification Of Endothelial Cell Immune-related Gene Signature for Lung Adenocarcinoma by Integrated Analysis of Single-cell and Bulk RNA Sequencing Data

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