Neutrophils Correlate with Hypoxia Microenvironment and Promote Progression of Non-Small-Cell Lung Cancer

2021 ◽  
Author(s):  
Chunyan Zhang ◽  
Bingxiang Tang ◽  
Jianping Hu ◽  
Xiang Fang ◽  
Hongzhi Bian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients

Abstract Background: Hypoxia, a strong and selective pressure, has been involved in invasion, metastasis, and angiogenesis of tumor cells. Methods: Our study performed the transcriptome profiles of 666 non-small-cell lung cancer (NSCLC) patients with clinical parameters from 3 microarray datasets. Various bioinformatic approaches were combined to evaluate the immune cell infiltration in the high hypoxia risk patients. In addition, in vitro experiments were performed to assess the effects of TANs on NSCLC cells proliferation, migration and invasion and to reveal the underlying mechanisms.Results: To develop a prognostic prediction model for NSCLC patients, we divided NSCLC into two groups (Cluster1/2) based on the expression profiles of hypoxia-associated genes. Compared with the Cluster1 subgroup, the Cluster2 had a worse prognosis. Significant enrichment analysis revealed that PI3K/AKT/mTOR signaling pathway and tumor-associated neutrophils (TANs) were highly related to hypoxia microenvironment. Eleven hypoxia-related genes were scored by LASSO COX regression to yield risk scores, and we revealed a significant difference in overall survival (OS) between the low- and high-risk groups. The receiver operating characteristic (ROC) curve and calibration curves suggested that the risk score can predict survival in NSCLC. Mechanistically, CXCL6 in hypoxic cancer cells promoted the migration of TANs in vitro, and in turn promote NSCLC cells proliferation, migration and invasion. Conclusions: In summary, this study revealed a 11‐hypoxia gene signature that predicted OS of NSCLC patients, and improved our understanding of the role of TANs in hypoxia microenvironment.

scholarly journals Epigenetic control of INSL4 promotes cell growth and invasiveness in Non-Small-Cell Lung Cancer

2020 ◽  
Author(s):  
Damiano Scopetti ◽  
Danilo Piobbico ◽  
Cinzia Brunacci ◽  
Stefania Pieroni ◽  
Guido Bellezza ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Relaxin Family ◽  
Nsclc Patients

Abstract Background Non-Small Cell Lung Cancer accounts for 80–85% of all forms of Lung Cancer as leading cause of cancer-related death in human. Despite remarkable advances in the diagnosis and therapy of Lung Cancer, no significant improvements have thus far been achieved in terms of patients’ prognosis. Here, we investigated the role of INSL4 – a member of the relaxin family –in NSCLC.Methods We permanently overexpressed INSL4 in NSCLC cells in vitro to analyse the growth rate and the tumourigenic features. We further investigated the signalling pathways engaged in INSL4 overexpressing cells and the tumour growth ability by studying the tumour development in a patient derived tumour xenograft mouse model. Results We found a cell growth promoting effect by INSL4 overexpression in vitro in H1299 cells and in vivo in NOD/SCID mice. Surprisingly, in NSCLC-A549 cells, stable INSL4 overexpression has not showed similar effect, despite has an INSL4-mRNA expressed up to 22.000 fold more respect H1299. The INSL4-mRNA analysis of eight different NSCLC-derived cell lines, has revealed a great discrepancy between the amount of INSL4-mRNA and specific protein. Notably, similar result has been observed in studied NSCLC patients analysing and comparing INSL4 mRNA and protein expression. However, in a cohort of NSCLC patients, we found a significant inverse correlation between INSL4 expression and Overall Survival.Conclusions By combining the results from the in vitro and in vivo models and in silico analysis in patients whose NSCLCs adenocarcinoma spontaneously expressed high levels of INSL4 our results suggest that epigenetic modifications that affect INSL4 does not allow to assess precision therapy in selected patients without consider protein INSL4 amount.

scholarly journals miR-34c-3p targets CDK1 a synthetic lethality partner of KRAS in non-small cell lung cancer

2020 ◽  
Author(s):  
Francesco Palma ◽  
Alessandra Affinito ◽  
Silvia Nuzzo ◽  
Giuseppina Roscigno ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Synthetic Lethality ◽  
Small Cell ◽  
In Vitro Assays ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Lung cancer is still the leading cause of death by cancer worldwide despite advances both in its detection and therapy. Multiple oncogenic driver alterations have been discovered, opening the prospective for new potential therapeutic targets. Among them, KRAS mutations represent the most frequent oncogene aberrations in non-small cell lung cancer (NSCLC) patients with a negative prognostic impact, but effective therapies targeting KRAS are not well characterized yet. Here, we demonstrate that the microRNA miR-34c-3p is a positive prognostic factor in KRAS-mutated NSCLC patients. Firstly, looking at the TGCA dataset, we found that high miR-34c-3p expression correlated with longer survival of KRAS-mutated NSCLC patients. In vitro assays on immortalized and patient-derived primary NSCLC cells revealed that miR-34c-3p overexpression increased apoptosis and lowered proliferation rate in KRASmut cells. Computational analysis and in vitro assays identified CDK1, one of the most promising lethal targets for KRAS-mutant cancer, as a target of miR-34c-3p. Moreover, the combination of CDK1 inhibition (mediated by RO3306) and miR-34c-3p overexpression resulted in an additive effect on the viability of KRASmut-expressing cells. Altogether, our findings demonstrate that miR-34c-3p is a novel biomarker that may allow tailored treatment for KRAS-mutated NSCLC patients.

Initial safety and efficacy results of erlotinib in previously treated patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18183-18183
Author(s):  
S. Zhou ◽  
C. Zhou ◽  
L. Yan ◽  
Q. Xu ◽  
J. Xu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Previously Treated ◽  
Nsclc Patients ◽  
Severe Rash

18183 Background: Erlotinib is an orally available selective HER1/EGFR tyrosine kinase inhibitor. In the BR.21 trial, erlotinib significantly improved survival and quality of life in non-small cell lung cancer(NSCLC) patients (pts). The study evaluated the initial efficacy and safety of erlotinib in previously treated advanced or metastatic NSCLC patients in Shanghai, China. Methods: Eligibility criteria included stage IIIb/IV or recurrent NSCLC pts who failed from prior chemotherapy, PS = 0–2, weight loss less than 5%, and no urgent symptoms. Pts received oral erlotinib 150 mg po/day until objective or symptomatic progression. Results: 50 pts were enrolled from Oct 1 to Sept 30. Demographics: M 68%/F 32%; median age 55 y [range 28–68]; stage IV 86%; PS 0/1/2:2 (4%)/44 (88%)/4 (8%); adenocarcinoma/non-adenocarcinoma 39 (78%)/11 (22%); smoking status: 26 (52%) /no 24 (48%). The major toxicity was rash: 48 (96%), 10 (20%) of them are grade 3/4; other toxicity included grade 1/2 diahhrea: 5 (10%); grade 1/2 liver dysfunction: 4 (8%); grade 2 leucocytopenia: 2 (4%); grade 1 thrombocytopenia: 1(2%); fatigue and dyspnea. 3 patients discontinued for dyspnea, pneumonitis and fatigue respectively. No pts had pulmonary fibrosis and dose reduction. 47 pts were followed long enough for efficacy evaluation, which indentified 18 (38%) with PR, 21 (45%) with SD, 8 (17%) with PD. Subgroup analysis showed the resposes to erlotinib have no relation with gender, age, smoking status, performance status, histology and stages, however, significant difference existed in the subgroup patients with severe rash and less symptoms such as dyspnea and fatigue ( Table 1 ). Conclusions: Erlotinib is active and well tolerated in patients with advanced NSCLC failed to previously chemotherapy. Preliminary results suggest patients with severe rash, less dyspnea and fatigue are accociated with better response. The study in ongoing. Table 1 Response of erlotinib in advanced treated NSCLC pts. * P values less than 0.05. [Table: see text] No significant financial relationships to disclose.

scholarly journals LncRNA PLAC 2 downregulated miR-21 in non-small cell lung cancer and predicted survival

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Huan Xia ◽  
Ming Xiu ◽  
Jinying Gao ◽  
Hongyu Jing
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Migration Ability ◽  
Invasion And Migration ◽  
Over Expression ◽  
Nsclc Patients

Abstract Background LncRNA PLAC2 has been characterized as a tumor suppressive lncRNA in glioma. We investigated the role of PLAC2 in non-small cell lung cancer (NSCLC). Methods A total of 187 NSCLC patients were admitted by The First Hospital of Jilin University from December 2010 to December 2014. All the patients were diagnosed by histopathological approaches. Transient cell transfections, RT-qPCR, invasion, and migration ability measurement, were applied for the experiments. Results PLAC2 was down-regulated, while miR-21 was up-regulated in NSCLC tissues compared to non-cancer tissues. Low PLAC2 levels in NSCLC tissues were associated with poor survival of NSCLC patients. PLAC2 and miR-21 were inversely correlated, and PLAC 2 over-expression in NSCLC cells resulted in the down-regulation of miR-21. However, miR-21 over-expression did not significantly affect PLAC2 expression. In addition, PLAC2 over-expression resulted in decreased migration and invasion rates of NSCLC cells. MiR-21 over-expression played the opposite role and attenuated the effects of PLAC2 over-expression. Conclusions In conclusion, lncRNA PLAC2 down-regulated miR-21 in NSCLC and inhibited cancer cell migration and invasion.

scholarly journals Analysis of Long Non-Coding RNA Expression Profiles in Non-Small Cell Lung Cancer

2016 ◽  
Vol 38 (6) ◽  
pp. 2389-2400 ◽  
Author(s):  
Li Wang ◽  
Zhenhong Chen ◽  
Li An ◽  
Yajuan Wang ◽  
Zhijian Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Differentially Expressed ◽  
Expression Level ◽  
Small Cell Lung ◽  
Normal Tissues ◽  
Nsclc Patients

Background/Aims: Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. However, the role of lncRNA expression in human Non-small cell lung cancer (NSCLC) biology, prognosis and molecular classification remains unknown. Methods: We established the IncRNA profile in NSCLC by re-annotation of microarrays from the Gene expression omnibus database. Quantitative real-time PCR was used to determine expression of LINC00342. Results: 6066 differentially expressed IncRNAs were identified and we found a novel IncRNA, LINC00342 was significantly up-regulated in NSCLC tissues compared with normal tissues. We confirmed the over-expression of LINC00342 in a cohort of NSCLC patients and found LINC00342 expression level was positively correlated with lymph node metastasis and TNM stages. Furthermore, in a large online database of 1942 NSCLC patients, high expression of LINC00342 indicated poor Overall survival (HR = 1.28, 95% CI: 1.13-1.45) and post progression survival (HR = 1.43, 95% CI: 1.09-1.88). Bioinformatics analyses showed that LINC00342 was co-expressed with different protein-coding genes in NSCLC and normal tissues. Additionally, gene set enrichment analyses found that PTEN and P53 pathways genes were enriched in the groups with higher LINC00342 expression level. By small interfering RNAs mediated silence of LINC00342, proliferation ability was significantly inhibited in lung cancer cell line. Conclusion: To summary, our findings indicate that a set of IncRNAs are differentially expressed in NSCLC and we characterized a novel IncRNA, LINC00342 which is significantly up-regulated in NSCLC and could be a prognostic biomarker.

Interleukin-6 is Increased in Breath Condensate of Patients with Non-Small Cell Lung Cancer

2002 ◽  
Vol 17 (2) ◽  
pp. 141-145 ◽  
Author(s):  
G.E. Carpagnano ◽  
O. Resta ◽  
M.P. Foschino-Barbaro ◽  
E. Gramiccioni ◽  
F. Carpagnano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Exhaled Breath Condensate ◽  
Small Cell ◽  
Exhaled Breath ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients ◽  
Breath Condensate

Despite recent advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), most patients still present with advanced stage disease at the time of diagnosis. Recent studies suggest that IL-6 is involved in the development of lung cancer. The aim of the present study was to investigate whether the measurement of IL-6 levels in the breath condensate of NSCLC patients could be used to bring forward the moment of diagnosis and to monitor the progression of the disease. Twenty patients with histological evidence of NSCLC (14 men and 6 women, age 63±8 years) and 15 healthy controls (8 men and 7 women, age 45±6 years) were enrolled in the study. IL6 was measured in the exhaled breath condensate of patients and controls by means of a specific enzyme immunoassay kit. Higher concentrations of exhaled IL-6 were found in NSCLC patients (9.6±0.3 pg/mL) than in controls (3.5±0.2 pg/mL). A statistically significant difference was observed between patients with NSCLC at different stages: higher concentrations of IL-6 (10.9±0.5 pg/mL) were found in patients with metastatic disease than in those with stage III (9.7±0.4 pg/mL), stage II (8.9±0.3 pg/mL) and stage I disease (7.9±0.3 pg/mL). These findings suggest that the measurement of IL-6 in the breath condensate of patients with NSCLC could be proposed as a parameter to take into account in early diagnosis and disease monitoring.

scholarly journals A Radioresponse-Related lncRNA Biomarker Signature for Risk Classification and Prognosis Prediction in Non-Small-Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jiahang Song ◽  
Shuming Zhang ◽  
Yuanyuan Sun ◽  
Junjie Gu ◽  
Ziqi Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Risk Model ◽  
Differential Expression Analysis ◽  
Small Cell ◽  
In Vitro Assays ◽  
Small Cell Lung ◽  
Nsclc Patients

Purpose. Radiotherapy resistance is now recognized as the major obstacle to the effective therapeutic management of non-small-cell lung cancer (NSCLC). As a single biomarker has limited effect in stratifying NSCLC patients, this research aimed to identify long non-coding RNAs (lncRNAs) correlated with radiotherapy response to ameliorate forecast of NSCLC prognosis. Methods. In a cohort of NSCLC patients with radiotherapy history (n = 96) from TCGA, genetic data of lncRNA expression profiling were performed. To identify radioresponse-related lncRNA sets which dysregulated significantly between radiosensitive (RS) and radioresistant (RR) groups, differential expression analysis was carried out. Cox relative regression was implemented to set up a radioresponse-related risk model. Moreover, we adopted survival analysis to measure the predictive potentiality of the prognosis model. Results. Four radioresponse-related lncRNAs (CASC19, LINC01977, LINC02471, and MAGI2-AS3) were screened to create a prognostic signature. Then, we described a lncRNA signature-based regulatory network and explored the correlation of the immune microenvironment and the signature. Additionally, in vitro assays uncovered inhibition of LINC01977 weakened radioresistance of NSCLC cells. Conclusion. We provided a novel radioresponse-related lncRNAs signature with excellent clinical potency for an effective prognostic forecast of patients.

scholarly journals Long noncoding RNA LINC01703 exacerbates the malignant properties of non-small-cell lung cancer by upregulating MACC1 in a microRNA-605-3p-mediated manner

2021 ◽  
Author(s):  
Ziyi Wang ◽  
Xinyu Zhang ◽  
Xuedong Zhang ◽  
Xuedong Jiang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Long intergenic nonprotein coding RNA 1703 (LINC01703) has diagnostic significancein lung adenocarcinoma. However, its specific roles in non-small-cell lung cancer(NSCLC) and downstream mechanisms have not been investigated. In the current study,we characterized the role of LINC01703 in NSCLC malignancy and elucidated itsdetailed mechanism of action. LINC01703 expression was measured by qRT-PCR. Theregulatory effects of LINC01703 on the malignancy of NSCLC cells were assessed bymultiple functional experiments. The targeted interaction was confirmed by RNAimmunoprecipitation and luciferase reporter assays. Herein, overexpression ofLINC01703 in NSCLC was indicated in the TCGA database and further proven in ourcohort. Functional studies revealed that knocking down LINC01703 repressed cellproliferation, colony formation, migration and invasion in vitro, which wasaccompanied by the induction of apoptosis. The tumor growth of LINC01703-silencedcells was also inhibited in vivo. Mechanistic analyses revealed that LINC01703functioned as a competing endogenous RNA for microRNA-605-3p (miR-605-3p) inNSCLC cells, which thereby upregulated the miR-605-3p target metastasis associatedwith colon cancer 1 (MACC1). Rescue experiments highlighted that the regulatoryactions of LINC01703 ablation on NSCLC cells were abolished in response to miR-605-3p downregulation or MACC1 overexpression. In conclusion, LINC01703enhanced the aggressiveness of NSCLC cells by altering miR-605-3p/MACC1. Ourwork suggests the therapeutic potential of LINC01703/miR-605-3p/MACC1 in NSCLC.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non–small cell lung cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Li-Na Pan ◽  
Yun-Fang Ma ◽  
Jia-An Hu ◽  
Zhi-Hong Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

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