scholarly journals Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer—Search for Non-Invasive Diagnostic Biomarkers

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 425
Author(s):  
Jolanta Kryczka ◽  
Monika Migdalska-Sęk ◽  
Jacek Kordiak ◽  
Justyna M. Kiszałkiewicz ◽  
Dorota Pastuszak-Lewandoska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Non Invasive ◽  
Progression Marker ◽  
Diagnostic Potential ◽  
Nsclc Patients

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals Clinical Significance of Serum-Derived Exosomal LINC00917 in Patients With Non-Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Dani Xiong ◽  
Chuanlin Wang ◽  
Zhaohui Yang ◽  
Fusen Han ◽  
Huaibing Zhan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Diagnostic Potential ◽  
Nsclc Patients

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.

Co-occurrence of targetable aberrations in non-small cell lung cancer patients harboring MAP2K1 mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20059-e20059
Author(s):  
Alessandra Holzem ◽  
Lucia Nogova ◽  
Michaela A. Ihle ◽  
Claudia Wompner ◽  
Elisabeth Bitter ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Mek Inhibitors ◽  
Tp53 Mutations ◽  
Nsclc Patients

e20059 Background: MAP2K1 mutations are rare in non-small cell lung cancer (NSCLC) and considered to be mutually exclusive with known driver mutations. Activation of the MEK1-cascade might play a pivotal role in resistance to targeted inhibition of BRAF V600E, EML4-ALK and EGFR T790M. So far, however, only MAP2K1 K57N could be identified and linked functionally to resistance in preclinical models. Clinical trials combining specific inhibitors for predefined NSCLC subgroups with MEK inhibitors are ongoing. We sought to characterize frequency and type of MAP2K1-mutated NSCLC regarding curated targetable aberrations. Methods: Tumor tissue collected consecutively from 4590 NSCLC patients within the German Network Genomic Medicine (NGM) between 07/2014 and 07/2015 was analyzed for MAP2K1 mutations using next-generation sequencing (NGS) with a set of 102 amplicons in 14 genes. Clinical and molecular characteristics of these patients were determined and compared with an internal control group of NSCLC patients and an independent control group of The Cancer Genome Atlas (TCGA). Results: We identified 21 (0.5%) patients with MAP2K1 mutations. They were frequently found in adenocarcinomas (n = 20) and were significantly associated with smoking. The most common MAP2K1 mutation was K57N. Most of the patients (n = 16) had additional oncogenic driver aberrations, including mutations in ALK, EGFR or BRAF, ROS1 rearrangements and MET amplification. TP53 mutations were found in 11 patients. In only five patients (23.8%) MAP2K1 occurred exclusively. TCGA analysis revealed additional 10 patients with MAP2K1 mutations, whereof 9 had additional TP53 mutations and one had BRAF mutation. Whereof most patients in our cohort had stage IV NSCLC, all patients in TCGA were systemic treatment naive. Compared with local stages in TCGA, our findings strongly suggest that targetable co-occurring mutations might occur more frequently in advanced stage NSCLC patients. Conclusions: MAP2K1 mutations co-occur frequently with targetable aberrations in smoking stage IV patients. Combination of targeted therapy against known driver aberrations with MEK inhibitors might be a promising therapeutic approach for such patients.

scholarly journals The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 are risk factors for non- small cell lung cancer in Iranian population

2020 ◽  
Author(s):  
Neda KakaDezfuli ◽  
Ian M. Adcock ◽  
Shamila D. Alipour ◽  
Sharareh Seyfi ◽  
Babak Salimi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genomic Region ◽  
Small Cell ◽  
Iranian Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background: Lung cancer is a leading cause of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of study was to detect any correlation between those SNPs in Iranian NSCLC patients.Methods: In a small cohort study, 165 NSCLC patients and 147 non-cancer controls were enrolled between Apr 2015 – Sep 2019 at the Masih Daneshvari Hospital, Tehran-Iran. Allele frequencies from genomic DNA of blood PBMC was studied using PCR-RFLP and their association with the risk of lung cancer was evaluated.Results: The frequency of the C allele of the miR-146a rs2910164 polymorphism was increased in NSCLC patients (OR=1.56, 95%CI=1.10 -2.21, P= 0.012). In contrast, the frequency of the A allele of the miR-155 rs767649 polymorphism was significantly increased in the control group (TT vs. AA+AT: OR=0.58, 95%CI=0.35-0.98, P= 0.043).Conclusion: The findings of this study suggest that miR-146a rs2910164 and miR-155 rs767649 polymorphisms could be related with the risk of NSCLC in an Iranian population. However, a larger multi center study across Iran is needed to confirm these findings.

Metronomic antiangiogenetic biochemotherapy of non-small cell lung cancer patients with fractionated cisplatimum, oral etoposide, and bevacizumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19083-e19083
Author(s):  
C. Remondo ◽  
C. Migali ◽  
I. Martellucci ◽  
F. Carbone ◽  
V. Ricci ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Metronomic Chemotherapy ◽  
Small Cell ◽  
Control Group ◽  
Oral Etoposide ◽  
Small Cell Lung ◽  
Nsclc Patients

e19083 Background: Chemotherapy efficacy in advanced non small cell lung cancer (NSCLC) patients may be augmented if combined with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF) with anti-angiogenetic activity. Metronomic chemotherapy is a newest approach which employs cytotoxic drugs at lower doses with very close and regular administrations, which has shown anti-angiogenetic effects, epigenetic attenuation of cancer phenotype and immune-modulation. Metronomic chemotherapy with cisplatinum and oral etoposide (mPE) has been tested in NSCLC patients with promising results. We have thus investigated a newest biochemotherapy regimen with mPE + bevacizumab (mPEBev regimen) in advanced NSCLC patients. Methods: This is a phase IB/II trial designed to evaluate toxicity, anti-tumor and biological activity of bevacizumab given at escalating doses in combination with mPE chemotherapy. Twenty-six patients with inoperable NSCLC and an ECOG≤2 were enrolled in the study and received every 21 days, iv. cisplatinum (30 mg/sqm, days 1–3), oral etoposide (50 mg/sqm, days 1–15) and bevacizumab (day 3) at different dose levels (no antibody/control group; 2.5; 5; 7.5; and 10 mg/kg). Results: The treatment resulted very active in those patients who received bevacizumab with a 95% objective response rate (19/20), with a median time to progression of 7.55 months. There were two early deaths at higher bevacizumab dosages: one due to a cardiovascular accident (7.5 mg/kg) and another to lung hemorrhage (10mg/kg). We reported also 4 cases of psychic depression and 4 cases of pneumonia which evolved into lung cavitation. A magnetic resonance monitoring showed a significant treatment-related blood perfusion reduction in the tumor site. It was also observed a progressive decrease in VEGF, thrombospondin-1 levels which were not dependent upon bevacizumab dose and were not observed in the controls. Conclusions: mPEBev regimen resulted very active in advanced NSCLC patients. Our metronomic biochemotherapy regimen with lower bevacizumab doses (2.5–5 mg/Kg) deserves to be investigated in further phase II-III trials. No significant financial relationships to disclose.

Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small cell lung cancer: A phase II, open-label, multicenter, randomized study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8053-8053
Author(s):  
Kumar Prabhash ◽  
Kanaka Govind Babu ◽  
Ashok K. Vaid ◽  
Ranga Rao Rangaraju ◽  
Bhawna Sirohi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Open Label ◽  
Nsclc Patients

8053 Background: To evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods: This multicenter, open-label, phase II study, randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab (200 mg) was administered once weekly for 13 weeks during the first 2 phases with 4 cycles of chemotherapy; docetaxel (75 mg/m2) and carboplatin (area under the curve [AUC] = 5 mg/ml*min), every 3 weeks for a maximum of 4 cycles during the concomitant phase. The primary endpoint was objective response rate (ORR; sum of complete response [CR] and partial response [PR]). Secondary endpoints, overall survival (OS), and progression-free survival (PFS) were estimated using Kaplan-Meier method. Efficacy was evaluated on the intent-to-treat (ITT) and efficacy-evaluable (EE) sets. Safety was assessed from adverse events (AEs) and serious adverse events (SAEs) data. Results: ORR was significantly higher in the nimotuzumab group than in the control group in the ITT (54% vs. 34.5%; P=0.04) population. CR and PR were achieved in 3.6% and 50% patients, respectively, in the nimotuzumab group, and in 4% and 30.9% patients, respectively, in the control group. No significant differences in median PFS and OS were observed. Safety profiles were comparable between the 2 groups. Conclusions: Nimotuzumab plus chemotherapy significantly improved ORR as compared to chemotherapy alone; the combination was safe and well tolerated in stage IIIB/IV NSCLC patients.

Potential importance of Maackia amurensis agglutinin in non-small cell lung cancer

2013 ◽  
Vol 394 (7) ◽  
pp. 889-900 ◽  
Author(s):  
Sangeeta Mehta ◽  
Rakhee Chhetra ◽  
Radhika Srinivasan ◽  
Suresh C. Sharma ◽  
Digambar Behera ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung ◽  
Maackia Amurensis ◽  
Diagnostic Potential ◽  
Nsclc Patients

Abstract Maackia amurensis agglutinin is a NeuNAcα (2–3) Galβ (1–4) GlcNAc/Glc-specific lectin, which was shown to have diagnostic potential in cancers of different origin. In a previous report, we demonstrated that GM3 specific IgG from bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients interacted with ∼66kDa membrane glycoprotein band of NSCLC cell lines, which was also recognised by this lectin. This observation prompted us to assess the potential of Maackia amurensis agglutinin in NSCLC. Accordingly, we examined the reactivity of this lectin with NSCLC cell lines as well as the tissue biopsies and cells obtained from fine needle aspirations of NSCLC patients. Maackia amurensis agglutinin showed strong reactivity, specifically with cells and biopsy samples of NSCLC origin. Furthermore, this lectin was found to induce apoptosis in NSCLC cells. The mechanism of this lectin-induced apoptosis involved downregulation of Bcl-XL, upregulation of Bax, release of cytochrome c and activation of procaspase-3. Collectively our results have suggested that Maackia amurensis agglutinin may have the potential to serve as a unique probe for detection of NSCLC and also as a specific apoptosis-inducing agent in NSCLC cells.

scholarly journals The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Neda K. Dezfuli ◽  
Ian M. Adcock ◽  
Shamila D. Alipoor ◽  
Sharareh Seyfi ◽  
Babak Salimi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Iranian Population ◽  
Control Group ◽  
Small Cell Lung ◽  
Increased Risk ◽  
Nsclc Patients

Background. Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. Methods. In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated. Results. The rs2910164C allele (OR = 1.56, 95% CI = 1.10–2.21, p = 0.012 ) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, p = 0.034 , respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR = 0.57, 95% CI = 0.33–0.99, p = 0.048 ) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, p = 0.043 ) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR = 0.44, 95% CI = 0.21–0.90, p = 0.024 ). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC. Conclusion. Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

scholarly journals Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Louisa Stern ◽  
Erik Mueller ◽  
Eugen Bellon ◽  
Matthias Reeh ◽  
Rainer Grotelueschen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Characteristic Curve ◽  
Small Cell ◽  
Screening Tools ◽  
Small Cell Lung ◽  
Non Invasive ◽  
Nsclc Patients

AbstractLung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92% and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.

Sign in / Sign up

Export Citation Format

Share Document