Circulating miRNA-21 and miRNA-23a Expression Signature as Potential Biomarkers for Early Detection of Non-Small-Cell Lung Cancer

MicroRNA ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 206-215 ◽  
Author(s):  
Helal Fouad Hetta ◽  
Asmaa Mohammad Zahran ◽  
Engy A. Shafik ◽  
Reham I. El-Mahdy ◽  
Nahed A. Mohamed ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Significant Difference ◽  
Nsclc Patients ◽  
Plasma Mirna

Background and Aim:Lung Cancer (LC) is a major cancer killer worldwide, and 5-yr survival is extremely poor (≤15%), accentuating the need for more effective diagnostic and therapeutic strategies. Studies have shown cell-free microRNAs (miRNAs) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study aimed to identify differentially-expressed two miRNAs in the plasma of Non-Small Cell Lung Cancer (NSCLC) patients that might be a clinically useful tool for lung cancer early detection. miRNA-21 is one of the most abundant oncomirs. miRNA-23a functions as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC.Materials and Methods:A case-control study was conducted in Assiut University Hospital, Egypt, from 2017 to 2018. Plasma samples were obtained from 45 NSCLC patients. The expression level of miR-21 and miRNA-23a was detected by qRT-PCR and compared to 40 healthy control subjects. The relation between both miRNAs and clinicopathological parameters was evaluated.Results:The expression level of miR-21 and miRNA-23a was significantly up-regulated (36.9 ± 18.7 vs. 1.12 ± 0.84 and 24.7 ± 19.09 vs. 1.16 ± 0.45) in NSCLC compared to matched controls (P<0.0001each). There was a significant difference in the level of plasma miRNA-21 and miRNA- 23a expression between the different grades of the disease (P = 0.032 and P = 0.001, respectively). The plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with distant metastasis (n = 20) were significantly higher than those in the patients without metastasis (n = 25) (P<0.0001 each), the expression of miR-21 and miRNA-23a was significantly associated with tumor size (P = 0.001, P = 0.0001, respectively), but not significantly related to lymph node metastasis (P = 0.687 and 0.696, respectively). A positive correlation was observed between miRNA-21 and miRNA-23a (r = 0.784, P<0.01), There was no significant difference in the plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with different histopathological types.Conclusion:miR-21 and miR-23a might play an oncogenic role in LC and is a poor prognostic factor. Switching off miRNA-21 and miRNA-23a may improve the treatment of LC. Our results must be verified by large-scale prospective studies with standardized methodology.

scholarly journals Venous thromboembolism in non-small cell lung cancer patients who underwent surgery after induction therapy

2020 ◽  
Vol 68 (10) ◽  
pp. 1156-1162
Author(s):  
Yasunori Kaminuma ◽  
Masayuki Tanahashi ◽  
Eriko Suzuki ◽  
Naoko Yoshii ◽  
Hiroshi Niwa
Keyword(s):  
Lung Cancer ◽  
Venous Thromboembolism ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Induction Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Significant Difference

Abstract Objectives Lung cancer patients have been reported to have a high incidence of venous thromboembolism (VTE) and a high recurrence rate of VTE. However, there are no detailed reports of VTE in lung cancer patients who underwent surgery after induction therapy. We examined the incidence and clinical features of VTE in these patients. Methods We retrospectively evaluated 89 patients with non-small cell lung cancer who underwent surgery after induction therapy at our department between April 2009 and March 2018. The incidence of VTE, clinical features, and long-term prognosis were retrospectively examined. Results Among the 89 patients, 4 (4.5%) developed VTE, and there was no significant difference in the background characteristics between patients with and without VTE. All four patients developed VTE during preoperative treatment. In the patients with VTE, anticoagulant therapy with oral anticoagulants was administered after heparinization, and the median duration of anticoagulant therapy was 18.7 months. There were no cases of symptomatic VTE recurrence after surgery, regardless of lung cancer recurrence. Although the overall survival (OS) showed no significant difference between patients with and without VTE, the disease-free survival was significantly shorter in patients with VTE than in those without it (median 6.3 vs. 71.6 months, p < 0.01). Conclusions In induction cases, the incidence of VTE was 4.5%, and it can at least be stated that no symptomatic VTE developed or recurred after surgery. Patients with VTE in induction therapy had short progression-free survival and required careful follow-up after surgery.

Predictive biomarker of response to anti-PD-1 treatment in non-small cell lung cancer patients.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 148-148
Author(s):  
Xuan Zheng ◽  
Yi Hu ◽  
Junxun Ma ◽  
Fan Zhang ◽  
Danyang Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Response Evaluation ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Significant Difference ◽  
Nsclc Patients

148 Background: PD-1 inhibitors have shown significant clinical activity in different cancer types. However, responses in pts with NSCLC are variable, and insights are needed to identify a predictive biomarker of response with greater diagnostic accuracy. Here we tested the hypothesis tha tserum TNF-a level is predictive of response to anti-PD-1 treatment. Methods: NSCLC patients treated with nivolumab or pembrolizumab were studied. Pts received nivolumab (3mg/kg, q2w) or pembrolizumab ( 2mg/kg, q3w). Pts on anti-PD1 were classified as either responders (R) deriving clinical benefit (with SD, PR, CR) or non-responders (NR) not deriving clinical benefit (PD) based on RECIST criteria.Serum was collected at baseline; at 2-3 weeks after the first dose (early stage); and at the time of response evaluation. Serum TNF-a levels were determined by Luminex kit. Changes in serum TNF-a levels and their strength of association with response were compared with Non-parametric Analysis. Results: Evaluable plasma samples were collected from twenty-one NSCLC patients treated with nivolumab or pembrolizumab. There was no significant difference in baseline serum TNF-a levels in responders (n = 15) vs non-responders (n = 6). Between baseline and early stage ,serum TNF-a levels significantly increased in responders (P = 0.010), while in non-responders, no significant change was found. High early change rate of serum TNF-a levels ( > 50%) was observed only in responders(n = 7).At early stage, responders had significantly higher serum TNF-a levels than non-responders(P = 0.008). We found no significant difference in serum TNF-a levels at the time of response evaluation. Conclusions: Early changes in serum TNF-a levels and high serum TNF-a levels at early stage in non-small cell lung cancer patients correlate to response to anti-PD-1 treatment.

Comparison and analysis among expression of CRP and tumor markers in advanced non-small cell lung cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17126-17126
Author(s):  
W. Dong ◽  
X. Ren ◽  
P. Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Cell Lung Cancer ◽  
Squamous Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Significant Difference

17126 Background: To investigate the correlation of C-reactive protein (CRP) and tumor markers such as carcinoembryonic antigen (CEA), CA125, cytokeratin 19 antibody (Cyfra 21–1) in non-small cell lung cancer (NSCLC) patients. Methods: CRP, CEA, CA125, Cyfra 21–1 were measured in the serum of 79 patients with advanced non-small cell lung cancer (stage III and IV ) by independent samples t test. Results: It showed statistically significant difference (P < 0.05) in the level of CRP, CEA, CA125, Cyfra211 between lung cancer patients (25.21 ± 19.12 mg/L, 62.89 ± 53.96 ng/L, 46.36 ± 30.03 U/L, 6.85 ± 2.42 ng/L, respectively) and the control subjects. CRP, CA125 showed no significant difference between squamous carcinoma and adenocarcinoma (P = 0.832, 0.406, respectively). CEA was higher in adenocarcinoma than in squamous carcinoma (P = 0.002). Cyfra211 was lower in adenocarcinoma than in squamous carcinoma (P = 0.039). The increase of CRP was accompanied with the increase of CEA, CA125 and Cyfra211 (p < 0.05). At the same time, CRP elevated while CEA, CA125, Cyfra211 increased (p < 0.05). Conclusions: All of CRP, CEA, CA125 and Cyfra211 increased in advanced non-small lung cancer. Combined monitoring on CRP with CEA, CA125, Cyfra211 may be a complementary method in advanced non-small cell lung cancer patients. No significant financial relationships to disclose.

scholarly journals Serial Troponin for Early Detection of Nivolumab Cardiotoxicity in Advanced Non‐Small Cell Lung Cancer Patients

2018 ◽  
Vol 23 (8) ◽  
pp. 936-942 ◽  
Author(s):  
Matteo Sarocchi ◽  
Francesco Grossi ◽  
Eleonora Arboscello ◽  
Andrea Bellodi ◽  
Carlo Genova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Detection ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

scholarly journals Serum GRP78 as a Tumor Marker and Its Prognostic Significance in Non-Small Cell Lung Cancers: A Retrospective Study

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Xiao Ma ◽  
Wei Guo ◽  
Su Yang ◽  
Xiaoli Zhu ◽  
Jiaqing Xiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Late Stage ◽  
Small Cell ◽  
Clinicopathological Parameters ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Significant Difference

Introduction. Glucose-regulated protein 78 (78 kDa, GRP78), which is also known as immunoglobulin heavy chain binding protein (BIP), is a major chaperone in the endoplasmic reticulum (ER). The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival.Patients and Methods. A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS) time, and relapse-free survival (RFS) time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student’st-test, Kaplan-Meier, or Cox regression analyses.Results. The mean ± standard error (SE) value of GRP78 was 326.5 ± 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 ± 223.6,p=0.0001). There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS(p=0.1585). However, the OS of patients with higher GRP78 expression was significantly poorer(p=0.0334).Conclusions. GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer.

scholarly journals Genetic Variants of CLPP and M1AP Are Associated With Risk of Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianghan Li ◽  
Yiran Zou ◽  
Teng Li ◽  
Thomas K. F. Wong ◽  
Ryan T. Bushey ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

BackgroundSingle nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage.MethodsDNA extracted from normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients.ResultsWe identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P &gt; 0.05).ConclusionsSNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.

scholarly journals Diversity and heterogeneity of immune states in non-small cell lung cancer and small cell lung cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260988
Author(s):  
Shawn J. Rice ◽  
Chandra P. Belani
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Systemic Inflammation ◽  
Cell Lung Cancer ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

Blood-based biomarkers including systemic inflammation (SI) indicators or circulating factors (cytokines, chemokines, or growth factors) are associated with a poor prognosis for lung cancer patients. Collectively these biomarkers can predict the immune state of a patient. We wanted to define and compare the immune states of small cell and non-small cell lung cancer patients, in the hopes that the information gained could lead to overall improvements in patient care and outcomes. Specimens and data from 235 patients was utilized, 49 surgically resected non-small cell lung cancer (NSCLC) patients with no evidence of disease (DF), 135 advanced non-small cell lung cancer (NSCLC), 51 small cell lung cancer (SCLC). SI markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI) were determined from blood counts. Forty-seven plasma cytokines were measured using a multiplex bead-based assay. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox Proportional Hazards models. NSCLC patients had significantly high levels of SI markers than SCLC and DF patients, while NLR, PLR and SII were also higher in SCLC than DF patients. SI optimized marker values to differentiate SI value were; 6.04 (NLR), 320 (PLR), 1615 (SII), and 7.3 (SIRI). Elevated levels NLR (p<0.001), PLR (p<0.001), and SII (p = 0.018) were associated with a worse PFS and OS in NSCLC, while none of the markers were associated with PFS in SCLC patients. NSCLC patients with a poor outcome displayed heterogeneous immune states relative to systemic inflammation and circulating IL-6 markers. These groups could be distinguished based on the cytokines IL-8, TNFα, and IL-27. We identified heterogeneity of immune states in SCLC and NSCLC patients and in NSCLC patients with the poorest prognosis. This heterogeneity could be exploited to improve outcomes for these patients.

scholarly journals Pretreatment Albumin-to-Alkaline Phosphatase Ratio Is a Prognostic Marker in Lung Cancer Patients: A Registry-Based Study of 7077 Lung Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6133
Author(s):  
Birgitte Sandfeld-Paulsen ◽  
Ninna Aggerholm-Pedersen ◽  
Anne Winther-Larsen
Keyword(s):  
Lung Cancer ◽  
Alkaline Phosphatase ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

The albumin-to-alkaline phosphatase ratio (AAPR) is a novel promising prognostic marker in cancer patients. However, the evidence for its significance in lung cancer is scarce. Therefore, we assessed the prognostic value of the AAPR in a large cohort of lung cancer patients. Data on lung cancer patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and combined with data on the pretreatment serum AAPR level extracted from the clinical laboratory information system (LABKA). AAPR tertiles were applied as cutoffs. Cox proportional hazard models assessed the prognostic value of the AAPR. In total, 5978 non-small cell lung cancer (NSCLC) patients and 1099 small cell lung cancer (SCLC) patients were included. Decreasing AAPR level was significantly associated with declining median overall survival (OS) in NSCLC patients (medium vs. low AAPR, adjusted HR = 0.73 (95% confidence interval (CI) 0.68–0.79); high vs. low AAPR, adjusted HR = 0.68 (95% CI 0.62–0.73)) and in SCLC patients (medium vs. low AAPR, adjusted HR = 0.62 (95% CI 0.52–0.74); high vs. low, adjusted HR = 0.59 (95% CI 0.50–0.70)). In conclusion, the AAPR was an independent prognostic factor in NSCLC and SCLC patients. The correlation seems to be level dependent, with reducing survival found to be associated with decreasing AAPR level.

Sensitivity of microcavity array system for circulating tumor cells in lung cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21007-e21007
Author(s):  
Hirotsugu Kenmotsu ◽  
Masahito Hosokawa ◽  
Yasuhiro Koh ◽  
Tomoko Yoshino ◽  
Takayuki Yoshikawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cellsearch System ◽  
Lung Cancer Patients ◽  
Nsclc Patients

e21007 Background: Epithelial Cell Adhesion Molecule (EpCAM)-based enumeration of circulating tumor cells (CTCs) has prognostic value in solid tumors such as advanced breast, colon and prostate cancers. However, poor sensitivity has been reported in non-small cell lung cancer (NSCLC). We have developed a microcavity array (MCA) system integrated with a microfluidic device for recovery and enumeration of CTsC, regardless of EpCAM expression level. This system can isolate tumor cells on the basis of differences in size and deformability between tumor and hematologic cells. Methods: Paired peripheral blood samples were collected from metastatic lung cancer patients. CTCs were enumerated by EpCAM-based immunomagnetic capture (CellSearch, Veridex) and by the MCA system. In the MCA system, trapped cells were stained with Hoechst 33342, FITC-labeled anti-pan cytokeratin antibodies and PE-labeled anti-CD45 antibodies for subsequent imaging analysis. CTCs were defined as cells with round to oval morphology, a visible nucleus, positive staining for pan-cytokeratin and negative staining for CD45. We evaluated the sensitivity of the MCA system for detecting CTCs in lung cancer patients compared with the CellSearch system. Results: Twenty-two metastatic NSCLC patients and 13 small-cell lung cancer (SCLC) patients were enrolled into this study between April 2011 and January 2012. CTCs were detected using the MCA system in 17 of 22 NSCLC patients (count ≥1 per 7.5 ml) compared with 9 of 22 patients using CellSearch (p=0.013). On the other hand, CTCs were detected using MCA in all 13 SCLC patients compared with just 9 of 13 patients using CellSearch (p=0.012). More CTCs from NSCLC patients were detected by the MCA system (median 13, range 0-313 cells/7.5ml) than by the CellSearch system (median 0, range 0-37 cells/7.5ml) demonstrating statistical superiority (p=0.002, Wilcoxon test). Conclusions: Our results suggest that the MCA system is potentially superior to the CellSearch system for detecting CTCs in lung cancer patients and further clinical development should be considered.

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