scholarly journals Tumor-derived exosomal miR-155-5p and miR-658 in serum as diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Author(s):  
ZhiJun Zhang ◽  
XingGuo Song ◽  
Li Xie ◽  
KangYu Wang ◽  
YouYong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Early Stage Nsclc ◽  
Healthy Donors ◽  
Diagnostic Capacity ◽  
Auc Value ◽  
Nsclc Patients

Abstract Background Exosomal microRNAs (ExmiRNAs) provided a non-invasive and ideal method for cancer diagnosis. However, few studies identified the role of specific serum ExmiRNAs profiles in early non-small cell lung cancer (NSCLC) diagnosis, especially for 0 and I stage. Herein, the present study was designed to validate the novel serum ExmiRNAs as diagnostic biomarkers for early-stage NSCLC. Methods Serum exosomes were collected from the healthy donors and NSCLC patients by ultracentrifugation, and characterized with qNano, TEM, and western immunoblotting. Exosomal RNAs were subjected to miRNA array for evaluating the expression levels of miRNAs. Partly differently expressed serum exosomal miRNAs were verified by large-scale samples from 312 healthy donors and 318 NSCLC patients. Results The expression levels of ExmiR-155-5p and ExmiR-658 were significantly down-regulated in NSCLC patients compared to healthy donors (p < 0.0001 and p < 0.0001, respectively), and they could differentiate NSCLC patients from healthy donors with area under the ROC curve (AUC) of 0.716 and 0.728, respectively. In addition, combination of ExmiR-155-5p and ExmiR-658 could improve the diagnostic capacity with AUC value of 0.781. Moreover, ExmiR-155-5p and ExmiR-658 could differentiate early-stage NSCLC patients (0 and I stage) from healthy donors with AUC values of 0.668 and 0.735, respectively, combination could improve the diagnostic capacity with AUC value of 0.759. Specifically, the expression of ExmiR-155-5p was significantly decreased in patients with lymph node metastasis and distant metastasis (p = 0.0018 and p = 0.0077, respectively). Conclusions Our results identified that serum ExmiR-155-5p and ExmiR-658 were promising diagnostic biomarkers for early-stage NSCLC, and combination of them could improve the diagnostic capacity.

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.

Mutational landscape of early-stage non-small cell lung cancer patients using a 451 gene panel.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20048-e20048
Author(s):  
Guanxian Mao ◽  
Peng Xuxing ◽  
Wu Hao ◽  
Wang Junbing ◽  
Liu Suyue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Detection Rate ◽  
Early Stage ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e20048 Background: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Methods: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Results: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0%)0/39) for BRAF,5.7% (2/35) and 0%)0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53. Conclusions: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0% )0/39) for BRAF,5.7% (2/35) and 0% )0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53.

Global histone modifications predict prognosis of resected non-small cell lung cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7662-7662
Author(s):  
F. Barlesi ◽  
G. Giaccone ◽  
M. I. Gallegos-Ruiz ◽  
A. Loundou ◽  
S. W. Span ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Histone Modifications ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Histone 3 ◽  
Nsclc Patients

7662 Background: Epigenetic modifications, such as methylation and/or acetylation of histones, may contribute to the development and progression of cancer. We investigated whether histone modifications influence prognosis of non-small cell lung cancer (NSCLC). Methods: We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12 (H2BK12Ac), histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 (H4K8Ac), in resected tumor samples of 138 NSCLC patients. In addition, the genotype of a tandem repeat polymorphism in the histone 3 methyltransferase SMYD3 gene was determined using PCR and capillary electrophoresis. Data were analyzed using a recursive partitioning analysis (RPA). Results: The overall median expression of H3K4diMe, H2AK5Ac, H2BK12Ac, H3K9Ac, and H4K8Ac were 75, 10, 0, 25, and 80%, respectively. The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology (second node) and histone modifications (third node). H3K4diMe (< or =85% tumor cells), H3K9Ac (< or =68% tumor cells) and H2AKAc (< or =5% tumor cells) were retained by RPA. The SMYD3 genotype was not retained by RPA. The seven groups were associated with significantly different disease- free (p<0.0001) and overall survival (p<0.0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median from 10 months in adenocarcinoma, H3K9Ac=68%, to 147 months in non-adenocarcinoma, H3K4diMe=85%). Conclusions: The prognostic influence of global histone modifications is greater in early stage NSCLC and it may help in the selection of early stage NSCLC patients for adjuvant treatment and provides a rationale for the use of combination of standard chemotherapy with drugs interacting with histone modifications such as histone deacetylases (HDAC) inhibitors. No significant financial relationships to disclose.

scholarly journals Tumor-Derived Exosomal miR-620 as a Diagnostic Biomarker in Non-Small-Cell Lung Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Youyong Tang ◽  
Zhijun Zhang ◽  
Xingguo Song ◽  
Miao Yu ◽  
Limin Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Area Under The Curve ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Nsclc ◽  
Noninvasive Biomarker ◽  
Nsclc Patients

Background. Evidence has suggested the functional role of exosomal miRNAs in cancer diagnosis. This study aimed to determine whether the serum exosomal biomarkers can improve the diagnosis of patients with non-small-cell lung cancer (NSCLC). Materials and Methods. The exosomes were extracted from the serum of NSCLC patients (n = 235) and healthy donors (n = 231) using ultracentrifugation and then were evaluated by using transmission electron microscopy, qNano, and western blotting. The serum exosomal miRNA expression was validated using qPCR. Results. Exosomal miR-620 was significantly reduced in NSCLC and early-stage NSCLC patients ( P < 0.0001 ) when compared to that of healthy controls, with an area under the curve (AUC) of 0.728 and 0.707, respectively. Exosomal miR-620 expression showed an association with drinking ( P = 0.008 ) and distant metastasis ( P = 0.037 ). Additionally, the downregulated exosomal miR-620 showed association with chemotherapeutic effect ( P = 0.044 ). Conclusion. These findings suggest the serum exosomal miR-620 as a promising diagnostic and prognostic noninvasive biomarker in NSCLC patients.

scholarly journals Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Min Hu ◽  
Xiaojiang Sun ◽  
Yuanjun Liu ◽  
Yaoyao Zhu ◽  
Qinghua Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.

scholarly journals Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (10) ◽  
pp. 3067
Author(s):  
Dohun Kim ◽  
Yujin Kim ◽  
Bo Bin Lee ◽  
Dongho Kim ◽  
Ok-Jun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Negative Effect ◽  
Nsclc Patients

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16–9.17, p = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62–50.91, p = 0.13) to 15.52 (95% CI = 2.94–82.38, p = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.

scholarly journals Comparison of Oncologic Outcomes between Carbon Ion Radiotherapy and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 176
Author(s):  
Yuhei Miyasaka ◽  
Shuichiro Komatsu ◽  
Takanori Abe ◽  
Nobuteru Kubo ◽  
Naoko Okano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Propensity Score ◽  
Small Cell Lung Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Early Stage ◽  
Small Cell ◽  
Oncologic Outcomes ◽  
Comparison Study ◽  
Small Cell Lung ◽  
Early Stage Nsclc

Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.

scholarly journals Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2660-2667 ◽  
Author(s):  
Yen-Tsung Huang ◽  
Rebecca S. Heist ◽  
Lucian R. Chirieac ◽  
Xihong Lin ◽  
Vidar Skaug ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Massachusetts General Hospital ◽  
Early Stage ◽  
The United States ◽  
Small Cell ◽  
Genome Wide Analysis ◽  
Early Stage Nsclc ◽  
Genome Wide ◽  
Nsclc Patients

Purpose Lung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. Patients and Methods One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Results Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend = 3.80 × 10−12 and 2.48 × 10−7 for MGH and Norwegian cohorts, respectively). Conclusion Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

scholarly journals Stereotactic body radiation therapy versus surgery for patients with early-stage non–small cell lung cancer( ≤ 5cm): A systematic review and meta-analysis

2021 ◽  
Author(s):  
Yueling Zhou ◽  
Ping Wen ◽  
Yue Yu ◽  
Zhenyi Yang ◽  
Yixuan Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Meta Analysis ◽  
Small Cell ◽  
Survival Outcomes ◽  
Small Cell Lung ◽  
Early Stage Nsclc

Abstract Background: Stereotactic body radiation therapy (SBRT) is considered as the preferred treatment method for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is still a debate on the efficacy of SBRT and surgery. This meta-analysis aimed to compare survival outcomes of SBRT and surgery for early-stage NSCLC (≤5cm).Methods: A systematic review and meta-analysis were performed to compare survival outcomes of surgery and SBRT. And the pooled analysis was conducted with STATA 14.0 software. Results: Thirty-nine comparative studies were included for systematic review and twenty-eight of which for quantitative analysis. Compared with SBRT, overall survival (OS) was superior after surgical resection, included lobectomy, sublobar resection, video-assisted thoracoscopic surgery, and thoracotomy, for patients with early-stage NSCLC (≤5cm). And the results of subgroup analysis remained the support of surgery except for the OS of operable matched cohorts and the one matched cohort of age ≥75. However, the HR of OS showed a reduction from patients with unspecific age, ≥65 to ≥75 years old and histopathologically confirmed NSCLC to clinical NSCLC. Although cancer-specific survival and local control was superior after surgery, the recurrence rate of tumors, locoregional control, distant control, and regional control of matched patients demonstrated no significantly different outcomes between SBRT and surgery for early-stage NSCLC.Conclusions: Results show that surgery has superior OS, CSS and local control compared to SBRT for early-stage NSCLC. There is still necessary to explore the survival difference between SBRT and surgery for patients with different characteristics by large-sample, long-term follow-up randomized clinical studies.

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