scholarly journals MiR-30a sensitized lung cancer against neoadjuvant chemotherapy by depressing autophagy

2021 ◽  
Author(s):  
Xiao Lin ◽  
Xiaojing Lai ◽  
Wei Feng ◽  
Xiaofu Yu ◽  
Qing Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cell Lines ◽  
Combined Treatment ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Enhanced Sensitivity ◽  
H460 Cell ◽  
Nsclc Patients ◽  
Autophagic Proteins

Abstract Objective This study was aimed at exploring whether miR-30a enhanced sensitivity of non-small-cell lung cancer (NSCLC) cells against neoadjuvant chemotherapy through an autophagy-dependent way. Methods We totally recruited 304 NSCLC patients who have underwent chemotherapy, as well as 185 NSCLC patients who did not receive chemotherapy. NSCLC cell lines (i.e. H1299 and H460) were also purchased, and they were transfected by miR-30a mimic/inhibitor. Furthermore, cisplatin (DDP)/pemetrexed (PEM) resistance of NSCLC cells was assessed utilizing MTT assay, and autophagic proteins isolated from NSCLC tissues and cells were quantitated by western blotting. Results Lowly expressed miR-30a was reflective of lymph node metastasis, advanced TNM stage and poor 5-year survival among NSCLC patients treated by neoadjuvant chemotherapy (i.e. combined treatment of DDP and PEM) (P < 0.05). Moreover, DDP combined with PEM attenuated viability and proliferation, but, on the contrary, promoted autophagy of H1299 and H460 cell lines (P < 0.05). However, miR-30a undermined resistance of NSCLC cells against DDP and PEM (P < 0.05), and it suppressed DDP/PEM-induced autophagy and promoted DDP/PEM-triggered apoptosis of NSCLC cells (P < 0.05). Conclusions Intentionally elevating miR-30a expression was conducive to improving NSCLC prognosis after neoadjuvant chemotherapy, for its depressing drug-caused autophagy and resistance.

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 Expression and Diagnostic Efficacy of miR-126-5p and miR-34c-3p in Serum Extracellular Vesicles of Non-Small Cell Lung Cancer Patients

2021 ◽  
Author(s):  
Jie Zhao ◽  
Wenlu Hang ◽  
Qian Wang ◽  
Yonghong Xu
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell Lung Cancer ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Nsclc Patients

Abstract Background: Non-small cell lung cancer (NSCLC) is a disease with quite grave prognosis. This study explored the diagnostic efficiency of miR-126-5p and miR-34c-3p in serum extracellular vesicles (EVs) in NSCLC patients.Methods: Serum EVs were extracted from NSCLC patients and healthy people and verified. The expression of miR-126-5p and miR-34c-3p in serum EVs were tested. Correlation of miR-126-5p and miR-34c-3p expression and diagnosis, prognosis and pathological characteristics (age, gender, tumor size, clinical stage, and lymph node metastasis) of NSCLC patients was analyzed. The downstream targets of miR-126-5p and miR-34c-3p were predicted and their roles in diagnosis and prognosis of NSCLC patients were evaluated.Results: miR-126-5p and miR-34c-3p were poorly expressed in serum EVs of NSCLC patients and their low expressions were associated with clinical stage, lymph node metastasis and prognosis of NSCLC patients and could be used as biomarkers for diagnosis. As the common target genes of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 were highly expressed in serum EVs and were associated with poor prognosis in NSCLC patients.Conclusion: Lowly expressed miR-126-5p and miR-34c-3p in serum EVs of NSCLC patients can serve as biomarkers for diagnosis and are linked with prognosis. As common targets of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 are also associated with poor prognosis in NSCLC patients.

ALK amplification and crizotinib sensitivity in non-small cell lung cancer cell lines and patients report.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10556-10556 ◽  
Author(s):  
Kalai Khadija ◽  
Nathalie Auger ◽  
Beranger Lueza ◽  
Frederic Commo ◽  
Alexander Valent ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Cancer Cell Lines ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

10556 Background: ALK high copy number (HCN) seems to be a frequent event, described in 13-17% of Non-small cell lung cancer (NSCLC). The goal of this study was to describe ALK genomic aberrations on NSCLC patients and cell lines, to explore the ALK HCN response to crizotinib through in vitro assays and to report three patients case. Methods: 191 Paraffin embedded specimens from advanced NSCLC patients and 27 NSCLC cancer cell lines were screened for ALK copy number by fluorescent in situ hybridization (FISH). Crizotinib sensitivity was evaluated in 9 cell lines through WST1 assays and clonogenic tests. Three patients exhibiting ALK HCN were assessed for response to crizotinib. Results: EML4-ALK translocation was present in 22 pts (11.5%). 21 pts (11%) exhibited over 6 copies of ALK. 6 (22%) cell lines displayed more than 5 copies of ALK, 19 (70%) presented a gain of 3 or 4 ALK copy number, only one cell line exhibited normal ALK copies and one harbored EML4-ALK translocation. FISH with CEP2 revealed a polysomy of chromosome 2 in cases with ALK HCN.Out of the 9 cell lines tested, 4 ALK HCN cell lines (H661, A427, BEN, H1299) exhibited increased sensitivity for crizotinib vs. 3 low ALK copy number (LCN) cell lines (H1975, H1651, H1650) with a low sensitivity. Median IC50 with crizotinib values was1750 nM [300-2800nM] in ALK HCN cell lines vs 4500 nM [800-8000nM] in ALK LCN cell lines, p=0.35. 3 patients with ALK HCN tumor received crizotinib ( in 4th , 5th and 6th -line therapy) for 2, 3 and 5 months with stable disease as best response and clinical benefit in 2 pts. Conclusions: ALK HCN may predict sensitivity to crizotinib. A clinical study is planned in ALK HCN pts.

Genetic variants in NPAS2 gene and clinical outcomes of resectable non-small-cell lung cancer

2021 ◽  
Vol 17 (7) ◽  
pp. 795-805
Author(s):  
Yiwei He ◽  
Gang Wang ◽  
Qian Wang ◽  
Zheng Zhao ◽  
Lu Gan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Variants ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Nsclc Patients

Background: A series of studies have demonstrated that NPAS2 plays a critical role in the development and progression of several cancers. However, the association between genetic variants in the  NPAS2 gene and the clinical outcome of patients with non-small-cell lung cancer (NSCLC) has not been investigated. Methods: Six functional SNPs in NPAS2 were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 484 Chinese NSCLC patients undergoing surgery. Multivariate Cox proportional hazards model were used for the prognosis analysis. Results: We found that SNP rs2305158 exhibited a significant association with overall survival of NSCLC patients in the dominant model (hazard ratio [HR]: 0.68; 95% CI: 0.49–0.95; p = 0.02). Lymph node metastasis was significantly associated with increased death risk (HR: 1.73; 95% CI: 1.24–2.40; p = 0.001) in patients with the homozygous wildtype (WW) genotype of rs2305158. However, no significant association was observed between them in patients carrying a heterozygous variant (WV) or homozygous variant (VV) genotype of rs2305158. Finally, in the joint and interaction analysis, the patients carrying homozygous wildtype (WW) genotype and lymph node metastasis from N1 to N3 conferred a significant increased effect on death (HR: 2.29; 95% CI: 1.40–3.76; p = 0.001). Conclusions: Our results suggest that NPAS2 polymorphisms may serve as an independent prognostic marker for NSCLC patients.

scholarly journals Identification and Exploration of Serine Peptidase Inhibitor Kazal Type 1 (SPINK1) as a Potential Biomarker Correlated with the Progression of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Xinxin Zhang ◽  
Rongshuang Ai ◽  
Zhiqiang Ding ◽  
Zimeng Wang ◽  
Qian He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Small Cell ◽  
Nsclc Cell ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Potential Biomarker ◽  
Mrna And Protein Expression ◽  
Nsclc Patients ◽  
Normal Controls

Abstract Background Lung cancer is one of the most common malignancies worldwide and is the leading cause of cancer-related death. Approximately 85% of lung cancer patients represent a group of histological subtypes collectively known as non-small cell lung cancer (NSCLC).Methods To explore the molecular mechanisms underlying tumorigenesis and progression of NSCLC, mRNA expression profiles were downloaded from GEO database (GSE19804, GSE18842, GSE27262, and GSE43458) and differentially expressed genes (DEGs) in NSCLC tissues were analyzed by GEO2R. DEGs in NSCLC tissues were further analysed in TCGA (The Cancer Genome Atlas), GTEx (The Genotype-Tissue Expression Project) and IST (In Silico Transcriptomics) online databases. Serum of NSCLC patients and normal controls were collected and serum concentration of SPINK1 were analysed by ELISA. mRNA and protein expression levels of SPINK1 were analysed by qRT-PCR and western assays. siRNA targeting SPINK1 and normal controls were used for the silence of SPINK1 and GAPDH. CCK-8 assays were employed for cell proliferation detection. Flow cytometric analysis and western blot assays were conducted to assess cell cycle distribution and apoptosis. Western blot assays were performed for the evaluation of cell autophagy and signaling pathways.Results Among these DEGs, SPINK1 was distinctively up-regulated in NSCLC tissues, which was further validated in TCGA, GTEx and IST databases. Furthermore, serum SPINK1 concentration notably increased in NSCLC patients compared with normal controls. Besides, both mRNA and protein expression levels of SPINK1 significantly increased in human NSCLC cell lines A549 and H1299 compared with normal human bronchial epithelial cell line HBE. Silence of SPINK1 significantly inhibited proliferation of NSCLC cell lines, and exogenous addition of rhSPINK1 partially rescued proliferation suppressed by endogenous knockdown of SPINK1. Mechanistically, silence of SPINK1 could inhibit MEK/ERK signaling pathway, while rhSPINK1 could activate MEK/ERK signaling pathway and then promote proliferation of NSCLC cell lines. In addition, silence of SPINK1 also could activate cell autophagy and apoptosis.Conclusions Overall, our results suggested that SPINK1 may be a potential biomarker correlated with the progression of NSCLC.

scholarly journals Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241241
Author(s):  
Qingsong Wang ◽  
Liang Xu ◽  
Gang Wang ◽  
Lei Chen ◽  
Changping Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Nsclc Patients ◽  
The Relationship ◽  
Nrf2 Expression ◽  
High Expression Level

Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a transcription factor and regulates a wide array of antioxidant and stress-responsive genes. NRF2 has been widely implicated in different types of cancers, but only limited studies concerning the relationship between NRF2 expression and tumour invasion or prognosis in lung cancer. Therefore, we conducted a meta-analysis to determine the prognostic value of NRF2 in patients with non-small cell lung cancer (NSCLC). The relationship between NRF2 expression in NSCLC patients and clinicopathological features was also investigated. Overall survival (OS) and treatment response rate were evaluated using STATA software. Twenty eligible articles with 2530 lung cancer patients were included in this meta-analysis. The results revealed that high expression level of NRF2 was associated with pathologic distant metastasis (odds ratio (OR) = 2.64, 95% confidence interval (CI) 1.62–4.31; P < 0.001), lymph node metastasis (OR = 2.14, 95% CI: 1.53–3.00; P < 0.001), and tumour node metastasis (TNM) stage (OR = 1.95, 95% CI: 1.52–2.49, P < 0.001). High NRF2 expression was associated with low treatment response rate in platinum-based chemotherapy (HR = 0.11, 95% CI 0.02–0.51; P = 0.005). High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44–2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26–4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients.

scholarly journals Clinicopathological and Prognostic Significance of Maspin Expression in Resected Non-Small Cell Lung Cancer: A Meta-Analysis

2020 ◽  
Author(s):  
Yan Wang ◽  
Yi Wang ◽  
Yingxian Dong ◽  
Jialong Li ◽  
Guowei Che
Keyword(s):  
Lung Cancer ◽  
Prognostic Significance ◽  
Clinicopathological Characteristics ◽  
Small Cell ◽  
Small Cell Lung ◽  
P53 Expression ◽  
Node Metastasis ◽  
Resected Nsclc ◽  
Maspin Expression ◽  
Nsclc Patients

Abstract Objective To explore the association of maspin expression with clinical pathological parameters and prognosis in non-small cell lung cancer (NSCLC) who received the surgical therapy.Methods The EMBASE, Web of Science and PubMed were searched to identify eligible studies to 3 December, 2019. The correlation of maspin expression with clinicopathological characteristics and survival of resected NSCLC patients was assessed by the combined relative risk (RR) and hazard ratio (HR) with corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed via the Stata 12.0 software.Results A total of 12 articles involving 1771 patients were included. The results manifested that maspin was more prevalent in lung squamous cell carcinoma (SCC) (RR=0.36, 95% CI: 0.22-0.60, P＜0.001) and significantly associated with P53 expression (RR=1.50, 95% CI: 1.00-2.24, P=0.048), while no significant correlation of maspin with other clinicopathological parameters such as the gender, age, tumor size, lymph node metastasis, tumor node metastasis (TNM) stage or differentiation status was observed. As for the prognosis representing as overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS), only significant association between maspin and CSS (HR=1.58, 95% CI: 1.16-2.15, P=0.003) was revealed. However, the subgroup analysis for OS based on the histology demonstrated that maspin expression was an unfavourable and favourable prognostic indicator in lung adenocarcinoma (HR=3.36, 95% CI: 1.44-7.87, P=0.005) and SCC (HR=0.44, 95% CI: 0.27-0.71, P=0.001), respectively.Conclusion Maspin expression was correlated with histology type and P53 expression, but no certain association of maspin with other clinicopathological characteristics or prognosis was observed in resected NSCLC. More well-designed prospective researches with big samples are still needed to further assess the clinicopathological and prognostic significance of maspin in NSCLC patients undergoing surgical resection.

scholarly journals Clinical Significance of PIK3CA Gene in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yi Wang ◽  
Yan Wang ◽  
Jialong Li ◽  
Jue Li ◽  
Guowei Che
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell Lung Cancer ◽  
Pik3ca Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pik3ca Gene ◽  
Node Metastasis ◽  
Nsclc Patients

Aim. To explore the clinicopathological and prognostic role of PIK3CA gene mutation and expression in non-small-cell lung cancer (NSCLC) patients. Methods. A systematic and comprehensive literature search was conducted through EMBASE (via OVID), Web of Science, and PubMed. Relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to evaluate the relationship of the PIK3CA gene with clinicopathological parameters and the survival of NSCLC patients, respectively. Results. A total of 13 studies involving 3908 patients were analyzed in our study. Only lymph node metastasis status had an association with PIK3CA mutation (RR=2.823; 95% CI: 1.128-7.065; P=0.029). The results indicated that PICK3CA mutation was related with overall survival (OS) (HR=1.55; 95% CI: 1.13-2.13; P=0.007), progression-free survival (PFS) (HR=1.48; 95% CI: 1.06-2.08; P=0.023), and cancer-specific survival (CSS) (HR=2.63; 95% CI: 1.00-6.92; P=0.005). Furthermore, PIK3CA high expression was more prevalent in NSCLC patients with smoking history (RR=2.42; 95% CI: 1.04-5.61; P=0.040). However, no significant relation between PIK3CA expression and OS was found (HR=0.80; 95% CI: 0.58-1.12; P=0.193). Conclusion. PIK3CA mutation may affect lymph node metastasis and serve as a promising prognostic factor, and smoking may be related with PIK3CA high expression in NSCLC patients. However, more well-designed prospective researches are needed to verify the abovementioned findings.

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