scholarly journals Loss of stretch-activated channels, PIEZOs, accelerates non-small cell lung cancer progression and cell migration

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Zhicheng Huang ◽  
Zhiqiang Sun ◽  
Xueying Zhang ◽  
Kai Niu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Tumor Tissue ◽  
Small Cell ◽  
Piezo Channels ◽  
Nsclc Patients ◽  
Stretch Activated Channels ◽  
Human Nsclc

Abstract PIEZO channels are stretch-activated channels involved in wound sealing and cell proliferation in many cell types. A recent study focussing on lung cancer (LC), using next-generation sequencing analysis, has indicated that PIEZO functions were implicated in LC development. However, the expression and role of PIEZO channels in non-small cell LC (NSCLC) progression require elucidation. In the current study, we investigated the gene expression and alteration frequency in human NSCLC tissue, accessed the prognostic roles of PIEZO channels in NSCLC patients, and further studied the effect of PIEZOs in NSCLC cell proliferation and tumor growth in vivo. The mRNA expression of PIEZO1 and 2 was clearly decreased in NSCLC tumor tissue compared with that in matched adjacent non-tumor tissue. In human NSCLC tissues, PIEZO1 gene expression exhibits a highly deep deletion rate, and PIEZO2 mainly exhibits mutation in gene expression. High mRNA expression of PIEZO channels was found to correlate with better overall survival (OS) for NSCLC patients, especially for patients with lung adenocarcinoma (LUAD), but not for patients with lung squamous cell carcinoma (LUSC). The prognostic role of PIEZO channels was more sensitive in female patients than male patients, and more sensitive in patients at earlier stages than patients at latter stages. Knockdown of PIEZO1 or PIEZO2 in NSCLC cells significantly promoted cell migration in vitro and tumor growth in vivo. These results indicate the critical prognostic values of the PIEZO channels in NSCLC. This information will be beneficial to understand the pathological mechanism of NSCLC and to generate effective therapeutic approaches for NSCLC patients.

scholarly journals Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Fei Zhang ◽  
Xu Pei ◽  
Ke-Sang Li ◽  
Li-Na Jin ◽  
Fei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Evasion ◽  
Critical Role ◽  
Circular Rna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. Methods The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Results Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Conclusion Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

The role of social determinants on overall survival in advanced-stage non-small cell lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21117-e21117
Author(s):  
Andreas Bello ◽  
Neeharika Srivastava Makani
Keyword(s):  
Lung Cancer ◽  
Social Determinants ◽  
Small Cell ◽  
Financial Assistance ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Chi Square ◽  
Study Population ◽  
Nsclc Patients

e21117 Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. Many studies have evaluated the association of social determinants with outcomes in early-stage NSCLC. These studies have shown statistically and clinically significant associations between overall survival (OS) and other social factors (e.g marital status, educational attainment). The aim of our study was to better understand the role of various social determinants of health (SDH) on OS in advanced-stage NSCLC patients in a community oncology practice in Florida. Methods: In this retrospective study, 125 patients with stage III and IV NSCLC were recruited between January 1st, 2014 until December 31st, 2018. We performed both categorical and continuous analyses (Pearson’s chi-square and Kruskal-Wallis test, respectively) to evaluate the association between median OS and several independent variables, including; gender, race, marital status, insurance status, living status, receiving financial assistance (FA), alcohol use, and smoking histories. OS is defined as the date of diagnosis up to the date of death. Other confounders that were analyzed included histology, treatment modality, comorbidities, and performance status of the patients. Results: Of the total study population (n = 125), 60% identified as male with a mean age of 73 years for the study population. The majority of patients (89%) identified as white; 56% were married, and 81% lived with someone. 66% of patients had an HMO insurance plan, and 51% of patients obtained FA to help with treatment care costs. 47% of patients identified as former smokers and 54% denied any alcohol use. The median OS for the patient population was 0.756 years. Chi-square analyses revealed that patients who received FA were more likely to live longer than median OS as opposed to patients that did not receive FA (OR = 2.41, 95% CI [1.18, 4.96], p = 0.050). Kruskal-Wallis analyses demonstrated that patients receiving FA had nearly a two-fold increase in median OS compared to patients without financial assistance (median OS = 1.01 years vs. 0.545 years, respectively; p = 0.013). However, other social determinants evaluated did not have a significant impact on relative OS in advanced-stage NSCLC. Conclusions: Ultimately, our study concludes that receiving FA has a significant association with increased OS in advanced-stage NSCLC patients. This study highlights the importance of reducing the financial burden of advanced-stage NSCLC patients and how FA impacts patient outcomes. Future prospective cohort studies with a larger sample size are warranted to identify other SDH, as well as the underlying mechanisms affecting median OS, in patients with advanced-stage NSCLC.

scholarly journals Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 245 ◽  
Author(s):  
Yosuke Miura ◽  
Noriaki Sunaga
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Direction ◽  
Nsclc Patients

The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

Transthyretin (TTR) Suppressed Tumor Progression in Non-Small Cell Lung Cancer by Inactivating MAPK/ERK Pathway

2020 ◽  
Author(s):  
Dong-bin Wang ◽  
Xuan Li ◽  
Xi-ke Lu ◽  
Zhong-yi Sun ◽  
Xun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Clinical Care ◽  
Small Cell ◽  
Signal Pathways ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
In Vivo Experiments

Abstract Background: Lung cancer is a leading cause of cancer death around the world, while the Transthyretin (TTR) is a specific biomarkers for clinical diagnosis. However, its role in lung cancer remains to be unknown. Methods: In the present study, we made attempt to investigate effect of abnormal expression of TTR on Non-small-cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR.To further investigate the mechanisms underlying the potential role of TTR in NSCLC, we searched and verified several signal pathways . In vivo experiments, to verify the effect of TTR overexpression on tumors.Results: We finded that up-regulated TTR obviously suppressed cell proliferation, migration, invasion and increased apoptosis.Significant suppression of phosphor-MAPK/ERK was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating MAPK/ERK signaling pathway. In vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusions: Overall, our results suggest that TTR has a potential anti-tumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC.Above all, further understanding of TTR was useful for clinical care.

scholarly journals Significance of accurate hilar and intrapulmonary lymph node examination and prognostication in stage IA–IIA non-small cell lung cancer, a retrospective cohort study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wenyu Zhai ◽  
Fangfang Duan ◽  
Yuzhen Zheng ◽  
Qihang Yan ◽  
Shuqin Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Survival ◽  
Differentiation Degree ◽  
Stage Ia ◽  
Nsclc Patients

Abstract Background The examination of lymph nodes (LNs) plays an important role in the nodal staging of non-small cell lung cancer (NSCLC). For patients without LN metastasis, the main role of thorough LN examination is accurate staging, which weakens the effect of staging migration. To date, the role of hilar and intrapulmonary (N1) station LNs has not been fully appreciated. In this study, we aimed to confirm the significance of N1 LNs in long-term survival for stage IA–IIA NSCLC patients and to find the minimum number of LN to examine. Methods The data of patients who underwent radical lobectomy and were confirmed as having non-metastatic LNs from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of LNs examined. The Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors. Results The median number of resected N1 LNs was 8. The number of patients with 0–2 N1 LNs, 3–5 N1 LNs, 6–8 N1 LNs, 9–11 N1 LNs, and more than 11 N1 LNs examined was 181, 425, 477, 414, and 531, respectively. Sex (P = 0.004), age (P < 0.001), tumor size (P = 0.004), differentiation degree (P = 0.001), and number of N1 LNs examined (P = 0.008) were independent prognostic factors of overall survival. Gender (P = 0.006), age (P = 0.031), tumor size (P = 0.001), differentiation degree (P = 0.001), vascular invasion (P = 0.034), and number of N1 LNs examined (P = 0.007) were independent prognostic factors of disease-free survival. Compared with patients with 0–5 N1 LNs examined, patients with more than 5 N1 LNs examined had better OS (P = 0.015) and had better DFS (P = 0.015) if only a landmark 5-year follow-up was performed. Conclusion Increasing the number of N1 LN examination might improve the long-term survival of T1-2N0 NSCLC patients. These data indicate that at least 6 N1 nodes examined is an essential part in surgical and pathological management but cannot prove this. This finding should be confirmed in a large, prospective randomized clinical study.

scholarly journals Forkhead box 1 expression is upregulatedin non-small cell lung cancer and correlateswith pathological parameters

2016 ◽  
Vol 11 (1) ◽  
pp. 220-224
Author(s):  
Chongwei Wang ◽  
Chongbang Wang ◽  
Shufang Duan
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Forkhead Box ◽  
Nsclc Patients

AbstractObjectives: As the member of the Fox family of transcription factors, Forkhead box M1 (FoxM1) is known to be critical in pathogenesis and development of many solid tumors. However, the clinical value and expression pattern in non-small cell lung cancer (NSCLC) is still poorly understood. Methods: In this study, real-time PCR was mainly applied to examine the gene expression levels of FoxM1 in 120 pairs of clinical NSCLC tissues, which were classified into different groups according to smoking status, lymph node metastasis, and tumor grade. By utilizing the online Kaplan-Meier plotter, overall survival analysis was performed to study the correlation between FoxM1 expression and prognosis of lung cancer (LC) patients. Afterwards, the correlation of FoxM1 gene expression and the clinical pathological parameters was examined by κ2 test in these 120 NSCLC patients. Results: FoxM1 was found to be aberrantly upregulated in NSCLC patients, and its overexpression was correlated to groups designated as smokers, cases of positive lymph node metastasis and cases of advanced tumor grades. Online survival analysis showed that high expression of FoxM1 predicted shorter overall survival of NSCLC patients. Additionally, FoxM1 upregulation was statistically correlated with positive smoking history, lymph node metastasis and higher tumor grades. Conclusion: FoxM1 is overexpressed in cancerous tissues and is associated with the poor prognosis of NSCLC patients. Our results provide insights into the utility of FoxM1 as an important biomarker and prognostic factor for NSCLC.

scholarly journals Critical Role of Gα12 and Gα13 for Human Small Cell Lung Cancer Cell Proliferation In vitro and Tumor Growth In vivo

2010 ◽  
Vol 16 (5) ◽  
pp. 1402-1415 ◽  
Author(s):  
Marius Grzelinski ◽  
Olaf Pinkenburg ◽  
Thomas Büch ◽  
Maike Gold ◽  
Stefanie Stohr ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Critical Role ◽  
Small Cell ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Proliferation In Vitro

Role of cMET expression in non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18092-e18092
Author(s):  
Hyun Chang ◽  
Xianglan Zhang ◽  
Da Rae Kim ◽  
Gun Min Kim ◽  
Se Hyun Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Tumor Tissue ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr Tkis

e18092 Background: We performed this study to investigate whether activation of cMET is associated with sensitivity to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients. Methods: This retrospective study included 69 NSCLC patients with available tumor tissue, treatment response and survival data. cMET and hepatocyte growth factor (HGF) status was evaluated by immunohistochemistry. Results: A positive cMET, cMET[pY1003], cMET[pY1234/1235] and HGF were identified in 89%, 44%, 20% and 89% of cases, respectively. Positive cMET[pY1003] expression was associated with better objective response rate (OR) and clinical benefit rate (CBR) (OR, P = 0.033 and CBR, P = 0.039). Positive cMET[pY1234/1235] was significantly associated with a longer overall survival (OS) (P = 0.012) and time-to progression (TTP) (P = 0.031). Multivariable model confirmed that cMET[pY1234/235]-positive patients had a significant reduction in the risk of death and disease progression than cMET[pY1234/1235] –negative patients [OS; hazard ratio(HR)=0.29, P = 0.008 and TTP; HR=0.43; P=0.024] Conclusions: cMET expression in tumor tissue could be useful for predicting the clinical outcome of EGFR-TKIs treatment. Our results suggest that cMET expression in tumor tissue could be used to refine the selection of NSCLC patients expected to benefit from EGFR-TKIs treatment.

Analysis of a profile of lipid metabolism genes in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20619-e20619
Author(s):  
Maria Merino ◽  
Lara Fernández ◽  
Ana Ramirez de Molina ◽  
Juan Moreno ◽  
Gonzalo Colmenarejo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Lipid Metabolism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Profile ◽  
Poor Survival ◽  
Nsclc Patients

e20619 Background: Non- small cell lung cancer (NSCLC) is one of the tumors with the highest mortality rate. The underlying metabolic alterations involved in its carcinogenesis are becoming more interesting. According to this, the analysis of the dysregulation of genes involved in lipid metabolism (LM) is subject to a growing research. To evaluate a profile of genes involved in lipid metabolism in NSCLC, we analyzed the correlation of this gene expression profile with different clinical-pathological variables. Methods: We performed a retrospective analysis of 22 genes related to LM in samples of NSCLC as well as clinical-pathological features. Advanced NSCLC patients enrolled from 2008 through 2015 were included. Clinical and pathological data were collected from medical reports. This study was approved in our ethical committee and all patients signed the consent inform. Samples were deparaffinated and RNA was extracted using RNeasy FFPE Kit (Qiagen Gmbh, Germany). A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software (Integromics Inc., Madison, USA) was used to detect and determine the quality control and differential expression analyses of data. Quantification of gene expression was calculated with the 2–ΔCt method. The Kaplan–Meier method was used for survival probabilities, and the log-rank test was to test differences between subgroups. Results: Ninety patients with advanced NSCLC were included. Median age was 64, 68/90 (75%) were male; 46/90 (51%) were ECOG 1; 68/90 (75%) adenocarcinoma vs 22/90 (24%) squamous; 47/90 (52%) smokers and 34% former smokers; metformine intake was presented in 9/90 (10%) and statins 24/90 (27%). In retrospective RT-PCR analysis including a lipid metabolism gene profile of 22 genes, we obtained an overexpression of 2 genes (an Acyl-CoA sintetase and a adipocine encoding gene). They were significantly correlated with overall poor survival in the multivariate analysis (table). These results were confirmed in an in silico validation using 994 NSCLC patients from TCGA study. Conclusions: This is the first study demonstrating a significant relation with a poor survival between a metabolic lipid gene profile expression and survival in advanced non- small cell lung cancer [Table: see text]

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