Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Xu, Yiquan; Huang, Yina H.; Weng, Lihong; Zheng, Jiankun; Huang, Yi; Zhao, Yunan; Li, Hongru; Chen, Yu‐Sheng

doi:10.1007/s00432-019-03059-y

Cited by 8 publications

(11 citation statements)

References 46 publications

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“…34 Moreover, clinical data showed that rs26865 and rs3160 polymorphic variants of MLST8 in lung cancer patients indicated a more likely brain metastasis. 35 Thus, the two molecules may serve as potential biomarkers to predict a patient's brain metastasis, which will have a huge impact on clinical practice.…”

Section: Discussionmentioning

confidence: 99%

A Five Autophagy-Related Long Non-Coding RNA Prognostic Model for Patients with Lung Adenocarcinoma

Liu

Yang

2021

IJGM

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Purpose: Lung adenocarcinoma is the most common pathological type among non-small cell lung cancer. Although huge progress has been made in terms of early diagnosis and precision treatment in recent years, the overall 5-year survival rate of a patient remains low. In our study, we try to construct an autophagy-related lncRNA prognostic signature that may guide clinical practice. Methods: The mRNA and lncRNA expression matrix of lung adenocarcinoma patients were retrieved from the TCGA database. Next, we constructed a co-expression network of lncRNAs and autophagy-related genes. Lasso regression and multivariate Cox regression were then applied to establish a prognostic risk model. Subsequently, a risk score was generated to differentiate the high and low risk groups and a ROC curve and nomogram to visualize the predictive ability of the current signature. Finally, gene ontology and pathway enrichment analysis were executed via GSEA. Results: A total of 1,703 autophagy-related lncRNAs were screened and five autophagyrelated lncRNAs (LINC01137, AL691432.2, LINC01116, AL606489.1, and HLA-DQB1-AS1) were finally included in our signature. Judging from univariate (HR=1.075, 95% CI=1.046-1.104) and multivariate (HR=1.088, 95% CI=1.057−1.120) Cox regression analysis, the risk score is an independent factor for LUAD patients. Further, the AUC value based on the risk score for 1-year, 3-years, and 5-years, was 0.735, 0.672, and 0.662, respectively, indicating a reliable model. Drug sensitivity analysis revealed low risk patients were more sensitive to Gemcitabine and Gefitinib, while high risk patients had a better response to Paclitaxel and Erlotinib. Moreover, the lncRNAs included in our signature were primarily enriched in the autophagy process, metabolism, p53 pathway, and JAK/STAT pathway. Finally, a multi-omics analysis of correlated genes showed CFLAR overexpressed in the tumor sample, while GAPDH and MLST8 had a slightly higher expression in the normal sample. Conclusion: Overall, our study indicated that the prognostic model we generated had certain predictability for LUAD patients' prognosis and the related genes might be potential biomarkers and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

A Five Autophagy-Related Long Non-Coding RNA Prognostic Model for Patients with Lung Adenocarcinoma

Liu

Yang

2021

IJGM

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“…Several studies reported that ULK1 inhibits cancer metastasis by promoting autophagy and interacting with the mTOR/AMPK pathway ( 37 – 39 ). SIN1 and MLST8 are both subunits of mTORC1 and mTORC2 and participated in cancer cell migration and invasion ( 40 , 41 ). Here, KEGG analysis revealed that MYC target and mTORC1 signaling pathways were potentially suppressed by PAMR1 in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

Yang

et al. 2021

Front. Oncol.

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Peptidase domain containing associated with muscle regeneration 1 (PAMR1) is frequently lost in breast cancer samples and is considered as a tumor suppressor. The roles and mechanisms of PAMR1 in other types of cancers are still unclear. In our present study, we identified PAMR1 as an invasion-related regulator in cervical cancer. Public database and immunohistochemical (IHC) analysis showed that the expression level of PAMR1 in cervical cancer tissues was lower than that in normal cervix tissues and was negatively related to clinicopathologic features. The high expression of PAMR1 also predicted a better prognosis of cervical cancer patients. CCK8, Transwell, and wound-healing assays demonstrated that knockdown of PAMR1 facilitated the proliferation, migration, and invasion of cervical cancer cells. Additionally, gene set enrichment analysis (GSEA) showed a variety of cancer-related pathways potentially activated or suppressed by PAMR1. Moreover, we verified that PAMR1 inhibited MYC target and mTORC1 signaling pathways. In conclusion, our study revealed the suppressor role of PAMR1 in cervical cancer, providing a new insight into the molecular mechanism of cervical cancer progression.

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“…Li Q et al proved for the first time that genetic variations in the transforming growth factor-β (TGF-β), PI3K/protein kinase B (AKT) pathways were associated with an increased risk of brain metastasis in NSCLC patients ( 67 , 68 ). Recently, Xu Y et al also proved that single nucleotide polymorphisms in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway are significantly associated with increased risk of brain metastasis ( 69 ). Activity of mTORC1/2 is higher in patients with lung cancer with brain metastases ( 70 ).…”

Section: Lung Cancer Driver Genes and Brain Metastasismentioning

confidence: 99%

Advances in Lung Cancer Driver Genes Associated With Brain Metastasis

Kang

Jin

et al. 2021

Front. Oncol.

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Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer.

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Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Cited by 8 publications

References 46 publications

A Five Autophagy-Related Long Non-Coding RNA Prognostic Model for Patients with Lung Adenocarcinoma

A Five Autophagy-Related Long Non-Coding RNA Prognostic Model for Patients with Lung Adenocarcinoma

High Expression of PAMR1 Predicts Favorable Prognosis and Inhibits Proliferation, Invasion, and Migration in Cervical Cancer

Advances in Lung Cancer Driver Genes Associated With Brain Metastasis

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