scholarly journals Hsa_Circ_0054284 Functions as a Tumor Suppressor via The Mir-18a-3p/TIMP2 Pathway in Non–Small-Cell Lung Cancer

2021 ◽  
Author(s):  
Zhexuan Xu ◽  
Chunya Lu ◽  
Guojun Zhang
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pcr Assay ◽  
Qrt Pcr ◽  
Nsclc Patients

Abstract Background: Non-small cell lung cancer (NSCLC) patients are basically at an advanced stage once diagnosed. In this study, our aimed to identify a new biomarker for early diagnosis of NSCLC.Methods and materials: CircRNA array analysis was designed to study the expression patterns of circRNAs in three pairs of NSCLC tissues. The expression of hsa_circ_0054284 were detected in 30 paired NSCLC tissues and adjacent normal tissues by qRT-PCR assay. A549 and H520 cells were transfected with overexpression vector of hsa_circ_0054284 and negative control. CCK-8, transwell invasion and Cell apoptosis assay were using to explore the internal relationship among the hsa_circ_0054284, miR-18a-3p and TIMP2. TIMP2 expression level was detected by qRT-PCR assay and western blotting analysis.Results: Hsa-circ-0054284 overexpression suppressed A549/H520 cell proliferation and invasion and promoted apoptosis via downregulation of miR-18a-3p and targeting TIMP2. This might be one of the possible mechanisms, which hsa-circ-0054284 plays in NSCLC.Conclusion: The current study provides novel insights into the circRNA-related ceRNA network in NSCLC and the hsa-circ-0054284 biomarkers may be Early diagnosis in NSCLC patients.

Long intergenic noncoding RNA LINC00173 as a potential serum biomarker for diagnosis of non-small-cell lung cancer

2020 ◽  
Vol 29 (4) ◽  
pp. 441-451 ◽  
Author(s):  
Qian Yang ◽  
Shan Kong ◽  
Ming Zheng ◽  
Yuelan Hong ◽  
Jing Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Differentially Expressed ◽  
Diagnostic Biomarker ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Nsclc Patients ◽  
Combined Detection

BACKGROUND: Long intergenic non-coding RNA (lincRNA) belongs to a special type of RNA that is unable to encode proteins but has been proved to play a role in gene regulation and differentially expressed in various malignant tumors. OBJECTIVE: In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. METHODS: The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. RESULTS: The qRT-PCR analysis showed that the serum LINC00173 expression level in 108 NSCLC patients was higher than that in 91 healthy donors and 55 patients with benign pulmonary disease (BPD). And the area under the curve (AUC) of serum LINC00173 was 0.809 for the diagnosis of NSCLC (95% CI: 0.750–0.868, p< 0.001), 0.670 for BPD (95% CI: 0.584–0.756, P< 0.001), and 0.730 for small-cell lung cancer (SCLC, 95% CI: 0.636–0.825, P< 0.001). Besides, we established a diagnostic model of combined detection of LINC00173, CEA and Cyfra21-1, and found that combined detection of these indicators significantly improved the diagnostic efficiency. Analysis of the Clinicopathological parameters showed that high LINC00173 expression was correlated with histological typing of tumor, tumor metastasis and serum Cyfra21-1 levels. In addition, serum LINC00173 expression decreased in patients who received chemotherapy and rebound in recurrent NSCLC patients. CONCLUSION: Serum LINC00173 may prove to be a potential non-invasive auxiliary diagnostic biomarker for NSCLC patients.

scholarly journals Circulating CD15+LOX-1+ PMN-MDSCs are a potential biomarker for the early diagnosis of non-small cell lung cancer

2020 ◽  
Author(s):  
Xinyu Tian ◽  
Ting Wang ◽  
Qisi Zheng ◽  
Yue Tao ◽  
Lei Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Roc Curve ◽  
Small Cell ◽  
Cytokeratin 19 ◽  
Small Cell Lung ◽  
Potential Biomarker ◽  
Nsclc Patients

Aims: Non-small-cell lung cancer (NSCLC) is the most common clinical lung cancer. Polymorphonuclear-myeloid derived suppressor cells (PMN-MDSCs), which are the major population of MDSCs, are involved in NSCLC progression. Recently, it was found that lectin-type oxidized LDL receptor 1 (LOX-1) could identify humsn PMN-MDSCs. However, the role of CD15+LOX-1+ PMN-MDSCs in NSCLC early diagnosis has not been revealed. Here, we tried to confirm the application of the newly-identified CD15+LOX-1+ PMN-MDSCs in the early diagnosis of NSCLC. Methods: Flow cytometry (FCM) was used to detect the proportion of CD15+LOX-1+ PMN-MDSCs in the peripheral blood (PB) of healthy controls (HC) and NSCLC patients. The correlation of CD15+LOX-1+ PMN-MDSC frequency with levels of cytokeratin 19-fragments (CYFRA21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) was analyzed. Receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficacy of CD15+LOX-1+ PMN-MDSCs for NSCLC. Additionally, the association of CD15+LOX-1+ PMN-MDSC frequency with NSCLC prognosis/recurrence after surgery was explored. Results: The proportion of CD15+LOX-1+ PMN-MDSCs increased in PB of NSCLC patients. CD15+LOX-1+ PMN-MDSC proportion was positively correlated with levels of CEA and CYFRA21-1. The area under the ROC curve (AUC) of PMN-MDSC percentage was higher than CYFRA21-1, CEA and CA125. The proportion of CD15+LOX-1+ PMN-MDSCs decreased in patients after surgery. The frequency of CD15+LOX-1+ PMN-MDSCs was lower in NSCLC patients without recurrence compared to those with recurrence after surgery. Conclusions: Circulating CD15+LOX-1+ PMN-MDSCs are a potential diagnostic marker for NSCLC, and are associated with NSCLC prognosis and recurrence after surgery.

scholarly journals Detection of Mitochondrial DNA Copy Number in Plasma Exosomes of Patients with Non-small Cell Lung Cancer

2022 ◽  
Author(s):  
Le Thi Thanh Nhan ◽  
Nguyen Thuy Quynh ◽  
Le Lan Phuong ◽  
Bui Phuong Thao ◽  
Nguyen Thi Tu Linh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Mtdna Copy Number ◽  
Pcr Assay ◽  
Nsclc Patients

For the prevalence of lung cancer and its poor diagnosis, the seeking of the efficient biomarkers for this disease is an urgent requirement, especially from non-invasive samples such as plasma. The mitochondria DNA (mtDNA) copy number change has been evaluated as a potential indicator of cancer risk, however, there have been few studies regarding mtDNA in plasma derived exosomes. In this study, the mtDNA copy number was measured on 29 plasma exosome samples of patients with non-small cell lung cancer (NSCLC) and 29 plasma exosome samples of cancer-free controls by real-time PCR assay, then being statistically analyzed to evaluate the relationship between these figures and several pathological features of NSCLC patients. As the results, the existence of mtDNA in exosomes isolated from plasma was detected through PCR assay using primers covering most of the mtDNA length. The relative mtDNA copy numbers determined in the exosomes of the disease and control groups were 1619.1 ± 2589.0 and 1207.0 ± 1550.0, respectively, whereas these values in two disease stages were 783.6 ± 759.3 (stage I-II) and 2647.0 ± 3584.0 (stage III-IV). Comparing among these groups, the difference was only statistically significant between the disease groups of stage I-II and stage III-IV (p<0.05), the group of stage III-IV and the control group (p<0.05). Indeed, the mtDNA copy number is associated with tumor stage and stage N (p<0.05). On the other aspect, the smoking habit of NSCLC patients could be an underlying reason behind the alteration in mtDNA copy number in the plasma exosomes. In short, our study demonstrates that the mtDNA copy number in exosomes resourced from plasma could be a potential biomarker for the detection and prognosis of NSCLC.

Coexpression patterns of IDO-1, PD-L1 and EGFR in non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14279-e14279 ◽  
Author(s):  
Weili Wang ◽  
Chen Zhang ◽  
Liang Cheng ◽  
Jianyue Jin ◽  
Feng-Ming Spring Kong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Expression Patterns ◽  
Small Cell ◽  
Treatment Modalities ◽  
Small Cell Lung ◽  
Indoleamine 2 ◽  
Nsclc Patients

e14279 Background: Indoleamine-2, 3-dioxygenase (IDO), a well-established immune suppressor, may offset efficacy of immune checkpoint inhibitors (ICIs) such as programmed death receptor ligand-1(PD-L1) by inducing unfavorable tumor microenvironment. The unpredictability of one ICI response may partially due to the concomitant presence of other ICIs. Therefore, increasing interest has been focus on the dual ICIs or the combination of ICIs with conventional treatment modalities such as radiotherapy, chemotherapy as well as target therapy. This study aimed to study the coexpression patterns and significance of IDO-1, PD-L1 and epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). Methods: Patients with newly diagnosed NSCLC enrolled in three prospective surgery clinical trials were included in this study. The expressions of IDO-1, PD-L1 and EGFR were evaluated by immunohistochemistry (IHC). For positive cases, the percentile score and H-score were generated respectively from two independent pathologists. The descriptive analysis of Crosstab was used to compare the distributions of these biomarkers expression by pathological types. Results: A total of 117 patients (adenocarcinoma -54%, squamous cell carcinoma -32% and others -14%) with pretreatment tissue specimen available for IHC analysis were studied. Of these, 105 (90%) were from lung primary and 12 (10%) from distant metastasis sites. The expressions of IDO-1 (≥ 1%), PD-L1 ((≥ 1%) and EGFR (≥ 90% or intensity = 3) were identified in 43%, 40% and 52% of NSCLC patients. For IDO-1 and PD-L1, coexpression rates were 21% for co-positive and 37% for co-negative. However, there were still 42% patients showed isolated PD-L1 (20%) or IDO-1 expression (22%). The coexpression rates for EGFR and IDO-1 were 21% for co-positive and 26% for co-negative. The coexpression rates for EGFR and PD-L1 were 20% for co-positive and 25% for co-negative. 38% patients had a positive EGFR with either IDO-1 or PD-L1 positive. The expression patterns were not significant associated with clinical factors including pathological types and differentiation grades. Conclusions: IDO-1 and PD-L1 expression patterns may be useful in the selection of NSCLC patients for dual ICIs immunotherapy. The combinations of EGFR target therapy with immunotherapy may benefit some of NSCLC patients. However, testing expression status of EGFR and immune checkpoints becomes essential since majority of NSCLC patients exhibits EGFR positive with IDO-1 or PD-L1 negative patterns.

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Strategy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

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