Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer

2020 ◽  
Vol 58 (9) ◽  
pp. 1535-1545 ◽  
Author(s):  
Ning Wang ◽  
Wei Guo ◽  
Xingguo Song ◽  
Lisheng Liu ◽  
Limin Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Potential Candidate ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Metastatic Nsclc ◽  
Nsclc Patients

AbstractBackgroundExosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC).MethodsIn this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort.ResultsNSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC.ConclusionsThis novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.

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 Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy

2020 ◽  
Vol 12 ◽  
pp. 175883592093688
Author(s):  
Fan Zhang ◽  
Di Huang ◽  
Lei Zhao ◽  
Tao Li ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Platinum Based Chemotherapy ◽  
Paclitaxel Group ◽  
Nsclc Patients

Background: Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Methods: The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed. Results: Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [ p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status ( p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group ( p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) ( p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group. Conclusion: PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

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.

Is survival improving in stage IV non-small cell lung cancer?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6577-6577
Author(s):  
A. E. Birnbaum ◽  
T. Ng ◽  
B. O'Connor ◽  
A. Plette ◽  
D. Berz
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Time Period ◽  
Nsclc Patients

6577 Background: Non small cell lung cancer (NSCLC) represents the number one cause of cancer mortality in the United States. Over several decades clinical research has focused on the development of new, more active chemotherapeutic drugs to improve survival. Over the time period from 1994 to 2003 six drugs have been approved for the treatment of metastatic NSCLC. We are presenting a population based analysis of the survival in patients with metastatic NSCLC in the US from 1981–1990, 1991–1997 and 1998–2003. We also provide a pharmaco-economic view of this observation. Methods: We analyzed the SEER (Surveillance, Epidemiology, and End Results) program database for cancer specific survival rates in stage IV NSCLC patients who were diagnosed between 1980 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the year of diagnosis. Results: We identified 52,086 eligible patients in total. 8,950, 21,111 and 18,712 patients were diagnosed 1981 to1990, 1991 to 1997 and 1998 to 2003 respectively. The cox proportional hazard ratios were 0.97 (95% CI 0.94–0.99) and 0.85 (0.83–0.88) for the time periods 1991 to 1997 and 1998 to 2003, respectively, using the time period from 1981 to1990 as reference. This subtle increase in survival was strictly paralleled by increasing costs for the medical care of this patient population. Conclusions: The survival of stage IV NSCLC patients seems to be mildly improving, what is paralleled by increasing cost for the care of those patients. [Table: see text] No significant financial relationships to disclose.

scholarly journals Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Hang Li ◽  
Bin Li ◽  
Yunjian Pan ◽  
Yang Zhang ◽  
Jiaqing Xiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Folate Receptor ◽  
Circulating Tumor Cell ◽  
Small Cell ◽  
Potential Candidate ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundSurgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FR+CTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.MethodsIn this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FR+CTC analysis. FR+CTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FR+CTC level and the prognosis in these patients was evaluated.ResultsOverall, preoperative FR+CTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes (P = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FR+CTC level was significantly different (P = 0.028). Further, patients with lower preoperative FR+CTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FR+CTC level (RFS: not reached vs. 33.3 months, P = 0.018; OS: not reached vs. 72.0 months, P = 0.13). In a multivariate COX regression analysis, FR+CTC level (HR = 4.10; 95% CI, 1.23–13.64; P=0.022) and pathological stage (HR = 3.16; 95% CI, 1.79–10.14; P = 0.0011) were independent prognostic factors of RFS. Moreover, FR+CTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FR+CTC or adenocarcinoma subtype alone.ConclusionOur study demonstrated that the preoperative FR+CTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FR+CTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.

MicroRNA-137 and microRNA-29a expression in non-small cell lung cancer diagnosis and prognostic.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17501-e17501
Author(s):  
Zhao Ming
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Real Time ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Cancer Tissue ◽  
Rt Pcr ◽  
Small Cell Lung ◽  
Nsclc Patients

e17501 Background: Current staging methods are inadequate for predicting the outcome of treatment of non–small-cell lung cancer (NSCLC). We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Methods: We studied frozen specimens of lung-cancer tissue from 76 randomly selected patients who underwent surgical resection of NSCLC. Using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we chosed U6 as the internal control for real-time RT-PCR because it is invariant in clinical cancer specimens. We obtained microRNA137 and 29a expressions level in 76 NSCLC patients and evaluated diagnoisis value and the association between the level of expression and survival. Results: This microRNA137 is with diagnosis value, microRNA29a expression level signature is an independent predictor of the cancer relapse and survival of NSCLC patients. Conclusions: Our microRNA signature is closely associated with relapse-free and overall survival among patients with NSCLC.

scholarly journals Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

2020 ◽  
pp. 1-7
Author(s):  
Serdar Arici ◽  
Abdullah Sakin ◽  
Ruhper Cekin ◽  
Saban Secmeler ◽  
Nurgül Yasar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
De Novo ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Group A ◽  
Nsclc Patients

<b><i>Introduction:</i></b> The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. <b><i>Methods:</i></b> The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or &#x3e;30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. <b><i>Results:</i></b> The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (<i>p</i> = 0.268) and the median OS was 10.0 and 11 months, respectively (<i>p</i> = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. <b><i>Conclusion:</i></b> Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

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 Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Junqing Gan ◽  
Yanjing Li ◽  
Qingwei Meng
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Sequence Similarity ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundLung cancer remains a common malignancy and the leading cause of cancer-related deaths in the world. Although dramatic progress made in multimodal therapies, it still has a poor prognosis. The Family with sequence similarity 83 (FAM83) of poorly characterized proteins are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini, most of which significantly elevated levels of expression in multiple cancers. However, the expression and prognostic values of different FAM83 family in lung cancer, especially in non-small-cell lung cancer (NSCLC), have not been clarified.MethodsONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, cBioPortal, and STRING databases were utilized in this study.ResultsThe transcriptional levels of FAM83A/B/C/D/F/G/H were up-regulated in patients with NSCLC. A noticeable correlation was found between the over-expressions of FAM83A/B/D/F/H and clinical cancer stages in NSCLC patients. Besides, higher mRNA expressions of FAM83A/B/C/D/F/H were discovered to be expressively associated with overall survival (OS) in lung cancer patients, furthermore, FAM83A, FAM83C, and FAM83H in OS group achieved 0.9475/1, 0.971897/1, and 0.9454545/0.8974359 specificity/sensitivity in distinguishing short survivors from long survivors, respectively. Moreover, a high mutation rate of FAM83 family (51%) was also observed in lung adenocarcinoma (LUAD) patients, and genetic alteration in the FAM83 family was associated with shorter OS and disease-free survival (DFS) in LUAD patients.ConclusionOur results indicated that FAM83A/H might play important roles in NSCLC tumorigenesis and might be risk factor for the survival of NSCLC patients.

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