scholarly journals HAGLROS is overexpressed and promotes non-small cell lung cancer migration and invasion

2020 ◽  
Vol 50 (9) ◽  
pp. 1058-1067 ◽  
Author(s):  
Ying Chen ◽  
Tianle Shen ◽  
Xuping Ding ◽  
Lei Cheng ◽  
Liming Sheng ◽  
...  

Abstract Introduction Non-small cell lung cancer was one of the most common and deadly cancers worldwide. Long non-coding RNAs had been implicated in multiple human cancers, including non-small cell lung cancer. In this study, we focused on a novel long non-coding RNA, HAGLROS, in non-small cell lung cancer. Material and methods In this study, we used GEPIA dataset to analyse the expression levels of HAGLROS in non-small cell lung cancer samples and normal tissues. Then, we analysed Kaplan–Meier Plotter database to reveal the association between HAGLROS expression and overall survival time in patients with non-small cell lung cancer. Moreover, we used small interfering RNA-mediated knockdown to reduce HAGLROS expression in A549 and H1299 cells. Cell Counting Kit-8 assay was used to detect the effect of HAGLROS on cell proliferation. Transwell assays were used to determine the effect of HAGLROS on cell migration and invasion. Co-expression analysis and bioinformatics analysis were conducted to predict the potential functions of HAGLROS in non-small cell lung cancer. Results We identified HAGLROS was significantly overexpressed in non-small cell lung cancer samples compared to normal tissues. Higher expression of HAGLROS was significantly associated with shorter overall survival time in patients with non-small cell lung cancer. Moreover, we found knockdown of HAGLROS in non-small cell lung cancer cells remarkably suppressed tumour proliferation, migration and invasion. By conducting bioinformatics analysis, we found HAGLROS was involved in regulating multiple cancer-related pathways, including Spliceosome, DNA replication, cell cycle, chromosome segregation and sister chromatid segregation. Conclusions Our results for the first time demonstrated HAGLROS may serve as a target for new therapies in non-small cell lung cancer.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Xie ◽  
Congyu Xue ◽  
Shuai Guo ◽  
Lei Yang

MicroRNAs (miRNAs) regulate multiple cellular behaviors, and their aberrant expression is frequently associated with disease progression. This research focused on the effects of miR-520a on the development of non-small-cell lung cancer (NSCLC) and the molecules involved. Tumor and normal tissues from 24 patients with NSCLC were collected. Differentially expressed miRNAs between tumor tissues and normal tissues were screened using microarrays, and miR-520a was screened to be significantly poorly expressed in tumor samples. Artificial upregulation of miR-520a reduced proliferation, migration and invasion, and resistance to death of NSCLC A549 and H460 cells according to the MTT, EdU labeling, transwell, and flow cytometry assays, respectively. miR-520a upregulation suppressed growth and metastasis of xenograft tumors in vivo. The integrated bioinformatic analysis and dual luciferase assays suggested that miR-520a targeted ribonucleotide reductase subunit 2 (RRM2) mRNA and inactivated the Wnt/β-catenin signaling pathway in NSCLC cells. Upregulation of RRM2 enhanced the malignant behaviors of NSCLCs, but the oncogenic effects of RRM2 were blocked upon miR-520a overexpression. To conclude, this study evidenced that miR-520a inhibits NSCLC progression through suppressing RRM2 and the Wnt signaling pathway. This paper may offer novel insights into NSCLC treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangbo Chen ◽  
Wenguang Liu ◽  
Bao Liu

It is reported that ginsenosides have a significant anti-tumor effect on a variety of tumors. However, the role and mechanism of Rh7 in non-small cell lung cancer (NSCLC) are unclear. In this study, we aimed to study the anti-tumor effect of Rh7 on the proliferation and progression of NSCLC. Bioinformatics analysis showed that ILF3-AS1 was regulated by ginsenoside Rh7 in NSCLC. Down-regulation of ILF3-AS1 could significantly inhibit the proliferation, metastasis and invasion of NSCLC. In addition, ILF3-AS1 negatively controlled miR-212, which in turn targeted SMAD1 expression, thereby regulating NSCLC cell viability and apoptosis. Our results indicate that ILF3-AS1 can be used as a diagnostic and therapeutic target for non-small cell lung cancer. It is discovered for the first time that ginsenoside Rh7 inhibits the expression of ILF3-AS1 and exerts antitumor effects.


Author(s):  
Shelly Srivastava ◽  
Surendra Kumar Saini ◽  
S. K. Agarwal

Background: Outcome of various treatment regimen are dismal in non-small cell lung cancer. This analysis is done to find possible care in authors institutional set up and to see how these protocols have effect in Indian patients in term of toxicity.Methods: Medical records and data on patients who had been diagnosed with non-small cell lung cancer histologically or cytologically, and who had been treated with sequential chemoradiation and concurrent chemoradiation at the hospital from January 2007 to March 2015 was retrospectively reviewed and analyzed. Two groups of sequential chemoradiotherapy and concurrent chemoradiotherapy were formed and compared for outcomes.Results: Of the 114 evaluable patients in sequential chemoradiotherapy group, the median survival time was 16.0 months and the 1, 3- and 5-years overall survival were 57.0, 26.9 and 21.2%, respectively. Median progression free survival (PFS was 13.0 months and the 1, 3 and 5 years PFS were 52.6, 14.6 and 7.8%, respectively. In concurrent chemoradiotherapy group (105 patients), the overall median survival time was 15 months and the 1, 3- and 5-year overall survival were 56.2, 20.6 and 14.7%, respectively. Median PFS was 13 months and the 1, 3 and 5-year PFS were 48.8, 19.7 and 10.3%, respectively. Grade 3 and 4 toxicity in both regimen groups are same and statistically not significant.Conclusions: Analysis confirm dismal outcome with standard treatment and signifies to search for care beyond conventional chemoradiotherapy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20577-e20577
Author(s):  
Adina Estrin ◽  
Patricia Prince ◽  
Dylan Supina ◽  
Rami Ben-Joseph ◽  
Anne Boccuti ◽  
...  

e20577 Background: Previous studies have investigated overall survival (OS) among small cell lung cancer (SCLC) patients with data through 2015. Using data through mid-2019, this study strives to make the body of studies more current, and to provide more recent data on the baseline characteristics and OS of treated SCLC patients, stratified by stage at diagnosis. Methods: This retrospective cohort study identified adult patients with confirmed SCLC between January 1, 2016 - December 31, 2018 that initiated anti-cancer treatment using real-world data from electronic medical records (ConcertAI, including data from CancerLinQ, an initiative of the American Society of Clinical Oncology). Exclusion criteria included evidence of other primary cancer at baseline, no initial stage recorded, death prior to diagnosis, or participation in a clinical trial. Patients entered the cohort upon receipt of their first anti-cancer treatment after SCLC diagnosis and were assigned up to three progression intervals to assess overall survival for each progression-based line of therapy. Patients were followed until death, end of data, or end of the study period (June 30, 2019). Kaplan-Meier analyses were conducted to assess median survival time as estimated by the survival curve. Results: Characteristics among the 82 limited stage (LS) and 217 extensive stage (ES) patients at 1L treatment were similar; however, LS patients were slightly older (mean age: LS = 67.5, ES = 66.4), and ES patients had a higher comorbidity score given their metastatic disease status (mean score: LS = 3.9, ES = 7.3). Both groups had very similar ECOG performance scores prior to 1L (ECOG: 0-1 ≅ 40%, 2+ ≅ 25%, Missing ≅ 35%). For the 299 patients that began 1L treatment (LS = 82, ES = 217), median OS time was 8.41 months (LS = 12.35 months, ES = 7.98 months). For the 124 of the 299 patients who progressed and were treated with 2L therapy, median OS time was 4.30 months. For the 44 of the 124 patients that progressed and were treated with 3L therapy, median OS time was 3.88 months. Of the 299 treated patients, 216 died before the end of the study period, representing 57% of the LS patients and 78% of the ES patients. Conclusions: These results reveal a difference in OS between LS and ES patients treated in 1L. The short survival time in patients with later lines of therapy highlights the need for new treatments in 2L and 3L.[Table: see text]


2021 ◽  
pp. 827-838
Author(s):  
Wei Zou ◽  
Stephanie J. Yaung ◽  
Frederike Fuhlbrück ◽  
Marcus Ballinger ◽  
Eric Peters ◽  
...  

PURPOSE Identification of predictors for overall survival (OS) allows timely detection of clinical efficacy signals and therefore facilitates treatment decisions. We assessed the association between circulating tumor DNA (ctDNA) metrics and the primary end point of OS in a subset of previously treated patients with locally advanced or metastatic non–small-cell lung cancer, who underwent atezolizumab or docetaxel treatment in the open-label randomized phase III OAK trial. MATERIALS AND METHODS Plasma from 94 patients at baseline and at subsequent cycles of therapy every 3 weeks was analyzed retrospectively for ctDNA. ctDNA was measured by allele frequency and mutant molecules per milliliter (MMPM). Concordance between various per-sample metrics and clinical outcome were assessed using C index. RESULTS Of all the ctDNA metrics tested, the association of median MMPM at 6 weeks with OS in patients treated with atezolizumab or docetaxel had a C index > 0.7. The OS hazard ratios relative to high ctDNA above median MMPM within each arm were 0.28 (95% CI, 0.11 to 0.75) for atezolizumab and 0.19 (95% CI, 0.08 to 0.48) for docetaxel. For patients who had ctDNA median MMPM levels of < 4.79, the median survival time was more than 17 months in docetaxel-treated patients and the median survival time was not reached in the atezolizumab-treated patients. CONCLUSION ctDNA MMPM levels measured at 6 weeks post-treatment are associated with OS in advanced non–small-cell lung cancer. Our results suggest that ctDNA has the potential for a noninvasive early liquid biopsy predictor for OS that warrants further studies to demonstrate its utility in clinical development.


2021 ◽  
Vol 49 (10) ◽  
pp. 030006052110131
Author(s):  
Yong Yang ◽  
Guangda Yuan ◽  
Hongya Xie ◽  
Tengteng Wei ◽  
Donglin Zhu ◽  
...  

Objective To investigate the clinical significance of cyclin-dependent kinase 14 (CDK14) expression in patients with non-small cell lung cancer (NSCLC). Methods The present prospective observational study included 193 patients diagnosed with NSCLC between January 2010 and December 2014. NSCLC tumor tissues and paired paracancerous normal tissues were obtained from all patients. CDK14, thyroid transcription factor 1 (TTF-1), cytokeratin 5/6 (CK5/6), and Ki67 expression was measured via immunohistochemistry (IHC) Results CDK14 staining was strong (>3) in 129 patients (66.49%) and weak (≤3) in 64 patients (33.16%). The mean IHC scores were markedly higher in tumor tissues than in paracancerous tissues. Pearson’s analysis demonstrated that the IHC scores of CDK14 expression were positively correlated with TTF-1, CK5/6, and Ki67 scores. Kaplan–Meier analysis illustrated that 5-year overall survival was markedly longer in patients with weak CDK14 staining. TNM stage, pleural invasion, lymph node metastasis, CDK14 expression, and Ki67 expression were risk factors for 5-year overall survival in patients with NSCLC. Conclusion CDK14 overexpression portended poor outcomes in patients with NSCLC, and CDK14 expression was correlated with TTF-1, CK5/5, and Ki67 expression.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: In the present study, we sought to detect the expression of secreted fizzled-related protein-1 (SFRP1) and investigate its role in the progression and prognosis of patients with non-small cell lung cancer (NSCLC). Methods: The expression of SFRP1 at both mRNA and protein level were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Immunohistochemistry analysis, respectively. The relationship between SFRP1 expression and clinical factors of patients with NSCLC was analyzed by chi-square test. Transwell assay was conducted to determine the influences of SFRP1 on migratory and invasive of NSCLC cells. Kaplan-Meier analysis was used to describe the overall survival of NSCLC patients. Cox regression analysis was conducted to estimate the prognostic value of SFRP1 in NSCLC.Results: The expression of SFRP1 was down-regulated in NSCLC tissues compared to that in adjacent normal controls both at mRNA and protein level (P<0.05). And the low SFRP1 expression was related to the distant metastasis, vascular invasion and TNM stage. The overexpression of SFRP1 in vitro significantly inhibited the migration and invasion of NSCLC cells. The overall survival of patients with high SFRP1 expression was was proved to be longer than those with low expression (log rank test, P<0.001). In addition, univariate and multivariate analyses suggested that SFRP1 was an independent prognostic molecule marker for NSCLC patients. Conclusion: Taken together, our findings indicated that the decreased of SFRP1 could influence the cell migration and invasion as well as be regarded as an independent prognostic marker in NSCLC.


2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.


2017 ◽  
Vol 14 (1) ◽  
pp. 58-77
Author(s):  
Sevgi Gezici ◽  
Mehmet Ozaslan ◽  
Gurler Akpinar ◽  
Murat Kasap ◽  
Maruf Sanli ◽  
...  

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