Can serum thioredoxin levels predict sensitivity to platinum in lung cancer?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22062-e22062
Author(s):  
Vy Thuy Dinh ◽  
Medhi Wangpaichitr ◽  
Dao M. Nguyen ◽  
Maria Matsangou ◽  
Chunjing Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Sandwich Elisa ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Reagent Blank ◽  
Normal Healthy Individual

e22062 Background: Our laboratory has found that cisplatin resistant lung cancer cells possess high levels of ROS (reactive oxygen species). Low intracellular TRX1 (thioredoxin) levels due to increased secretion of the thioredoxin-1 (TRX1) is the primary reason for high intracellular ROS levels. We have further shown that reconstituting TRX1 protein in cisplatin-resistant cells can restore sensitivity to cisplatin. Conversely, silencing TRX1 in parental cells reduced the sensitivity to cisplatin (MCT11:604, 2012). Thus, it is possible that serum TRX1 levels may be a useful marker to predict sensitivity to platinum containing regimens. Methods: Serum samples were obtained before, during, and after platinum chemotherapy. TRX1 was determined by sandwich ELISA with two TRX1 antibodies. Samples, standards, and reagent blank were incubated with precoated plate (IBL). Labeled antibody solution was added followed by Chromagen substrate and subjected to plate reader. The value on normal healthy individual is less than 5 ng/ml. The lowest limit of detection is 1 ng/ml. Results: 11 patients (pts) were entered into the study. 6 pts had small cell lung cancer (SCLC) and 5 had non small cell lung cancer (NSCLC). 2 SCLC pts died before treatment and couldn’t be assessed and 2 pts are too early to assess response. In these lung cancer pts, the baseline levels ranged from 0 to 96.5 ng/ml. Thus far, 4 pts (1 SCLC and 3 NSCLC) who had baseline TRX1 levels of 0, 0, 0 and 3 responded to chemotherapy. An additional SCLC pt with very high levels of TRX1 (96) also responded to chemotherapy. However, this pt also had a recent operation for NSCLC and the baseline blood sample was obtained after the operation, which may not be the appropriate baseline. 2 pts with baseline TRX1 levels of 31.1 and 6.5 did not respond to treatment. TRX1 levels increased during chemotherapy, especially when given concurrently with radiation. However, in pts who responded, TRX1 levels decreased at the end of treatment. Conclusions: The study is currently ongoing. Our initial results suggest that low TRX1 levels may indicate possible future response to platinum containing regimens. While TRX1 levels may increase during treatment, in pts who respond to treatment, TRX1 levels often decrease back to baseline.

scholarly journals Metabolic Changes in Early-Stage Non–Small Cell Lung Cancer Patients after Surgical Resection

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3012
Author(s):  
Naseer Ahmed ◽  
Biniam Kidane ◽  
Le Wang ◽  
Zoann Nugent ◽  
Nataliya Moldovan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Surgical Resection ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Resonance Spectroscopy ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Post Surgery

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.

scholarly journals RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 139
Author(s):  
Caterina De Luca ◽  
Francesco Pepe ◽  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Luisella Righi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Clinical Samples ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Relevant Gene

Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC.

Detection of leucine-rich alpha-2-glycoprotein 1-containing immunocomplexes in the plasma of lung cancer patients with epitope-specific mAbs

2021 ◽  
pp. 1-10
Author(s):  
József Lázár ◽  
András Kovács ◽  
Ilona Tornyi ◽  
László Takács ◽  
István Kurucz
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Biomarker Discovery ◽  
Sandwich Elisa ◽  
Small Cell ◽  
Small Cell Lung ◽  
Reporter System ◽  
Lung Cancer Patients

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. With the expectation of improved survival, tremendous efforts and resources have been invested in the discovery of specific biomarkers for early detection of the disease. Several investigators have reported the presence of cancer-associated autoantibodies in the plasma or serum of lung cancer patients. Previously, we used a monoclonal-antibody proteomics technology platform for the discovery of novel lung cancer-associated proteins. OBJECTIVE: The identification of specific protein epitopes associated with various cancers is a promising method in biomarker discovery. Here, in a preliminary study, we aimed to detect autoantibody-leucine-rich alpha-2-glycoprotein 1 (LRG1) immunocomplexes using epitope-specific monoclonal antibodies (mAbs). METHODS: We performed sandwich ELISA assays using the LRG1 epitope-specific capture mAbs, Bsi0352 and Bsi0392, and an IgG-specific polyclonal antibody coupled to a reporter system as the detection reagent. We tested the plasma of lung-cancer patients and apparently healthy controls. RESULTS: Depending on the epitope specificity of the capture monoclonal mAb, we were either unable to distinguish the control from LC-groups or showed a higher level of LRG1 and IgG autoantibody containing immunocomplexes in the plasma of non-small cell lung cancer and small cell lung cancer subgroups of lung cancer patients than in the plasma of control subjects. CONCLUSIONS: Our findings underline the importance of protein epitope-specific antibody targeted approaches in biomarker research, as this may increase the accuracy of previously described tests, which will need further validation in large clinical cohorts.

scholarly journals Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshihisa Shimada ◽  
Jun Matsubayashi ◽  
Yujin Kudo ◽  
Sachio Maehara ◽  
Susumu Takeuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Stage I ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Initial Surgery

AbstractPD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome’s surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I–III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.

scholarly journals Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer

Oncotarget ◽  
2020 ◽  
Vol 11 (27) ◽  
pp. 2660-2668
Author(s):  
Sylvia A.A.M. Genet ◽  
Esther Visser ◽  
Ben E.E.M. van den Borne ◽  
Maggy Youssef-El Soud ◽  
Huub N.A. Belderbos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Diagnostic Accuracy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Samples

Proteomics analysis discovers biomarkers in serum months to years before small cell lung cancer: The HUNT study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20095-e20095
Author(s):  
Olav Toai Duc Nguyen ◽  
Maria Markaki ◽  
Christina Chatzipantsiou ◽  
Animesh Sharma ◽  
Vincenzo Lagani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Validation Cohort ◽  
Small Cell ◽  
Small Cell Lung ◽  
Discovery Cohort ◽  
Serum Samples ◽  
Sample Set ◽  
Early Diagnostic

e20095 Background: The high incidence and high mortality rate of small-cell lung cancer (SCLC) calls for identification of methods for early diagnosis. Searching of cancer-related proteins and proteins signature in biofluids is an emerging approach in early diagnostic of malignancies. In the present study we have used proteomics-based profiling of serum collected 2 months to 5 years before SCLC diagnosis to search for early diagnostic biomarkers. Methods: All serum samples in this study were obtained from the Nord-Trøndelag Health Study (HUNT) Research Centre’s Biobank. Discovery sample set (Cohort I): Serum samples from 12 individuals that subsequently developed SCLC and 12 matched controls were obtained. Validation sample set (Cohort II): Serum samples from 5 future SCLC patients and 5 matched controls were obtained. The serum samples in both cohorts were collected in a time frame of 2 months to 5 years before diagnosis. All controls included in the study were matched to the cases for smoking status (pack years and quit time), gender and age, and were cancer-free at least 5 years before blood sampling. All subjects were smokers or ex-smokers. Twenty (20) µl of serum was depleted of its high-abundant proteins and the cleaned-up peptides were analysed by LC- MS with an Orbitrap Elite mass spectrometer. Data were processed/analysed using MaxQuant software. Using Cohort I as training set, proteins most related to diagnosis were identified at first with limma univariate analysis. Reference and equivalent signatures were identified using JADbio with SES as feature selection algorithm. The JADbio matched pipeline with 50 repetitions for performance assessment (AUC with 95% CI) was used. Results: In each serum sample the analysis detected 435 proteins in Cohort I and 609 proteins in Cohort II. Reference signature for 12 SCLC future cases vs 12 matched controls had a conservative AUC of 0.686 (95% CI: 0.557, 0.765) in the discovery cohort. Three proteins in the reference and equivalent signatures were also found to be differentially expressed in validation Cohort II; all three proteins discriminated small-cell lung cancer patients from their respective controls (AUC 0.757-0.826 in the discovery Cohort I and AUC 0.68-0.84 in the validation Cohort II). Conclusions: The results indicate that differential levels of a few proteins in serum may help detecting SCLC 2 months to 5 years prior to clinical diagnosis. This is one of the first large-scale proteomics screening studies of pre-diagnostic serum of future SCLC patients. Further validation studies are in progress.

scholarly journals EP1.01-63 The Usefulness of “Serum” Samples to Detect EGFR T790M Mutation in EGFR-TKI-Resistant Non-Small Cell Lung Cancer

2019 ◽  
Vol 14 (10) ◽  
pp. S936-S937
Author(s):  
K. Kobayashi ◽  
K. Naoki ◽  
S. Ikemura ◽  
H. Yasuda ◽  
I. Kawada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serum Samples ◽  
T790m Mutation ◽  
Egfr Tki ◽  
Egfr T790m

scholarly journals A novel biosensor for the ultrasensitive detection of the lncRNA biomarker MALAT1 in non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Chen ◽  
Dongming Wu ◽  
Shihua Tu ◽  
Chaoyin Yang ◽  
DeJie Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Raw Materials ◽  
Cost Effective ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Prognosis ◽  
Screen Printed Carbon Electrode

AbstractLong non-coding RNAs (lncRNAs) have been proposed as diagnostic biomarkers for the screening of non-small cell lung cancer and monitoring disease progression. Accordingly, new, rapid, and cost-effective lncRNA biosensors that can be used clinically are urgently needed. Herein, a novel effective and ultrasensitive electrochemical biosensor was developed based on a gold nanocage coupled with an amidated multi-walled carbon nanotube (Au NCs/MWCNT-NH2)-decorated screen-printed carbon electrode (SPCE). Because of its large surface area, superior conductivity, and excellent biocompatibility, this SPCE Au NCs/MWCNT-NH2 lncRNA biosensor showed a wide linear range (10–7–10–14 M) and low limit of detection limit (42.8 fM) coupled with satisfactory selectivity and stability. Compared to traditional RT-PCR, the proposed method exhibits acceptable stability, good selectivity, is simpler to operate, has faster detection, and uses less costly raw materials. In summary, this biosensor may be a powerful tool for detecting lncRNAs for efficient clinical prognosis and cancer diagnosis.

scholarly journals Clinical Significance of Serum-derived Exosomal PD-L1 in Patients with Resected Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Yoshihisa Shimada ◽  
Jun Matsubayashi ◽  
Yujin Kudo ◽  
Sachio Maehara ◽  
Susumu Takeuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Stage I ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Initial Surgery

Abstract PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8 + tumor-infiltrating lymphocytes (CD8 + TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8 + TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8 + TILs (p = 0.001). Patients with serum exosomal PD-L1 ≥ 200 pg/mL tended to have a worse RFS than those with < 200 pg/mL in stage I patients (p = 0.056). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment, 75% of patients with ≥ 200 pg/mL demonstrated a significant response to PD-1 inhibitors. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and be used to assess clinical outcomes in patients with NSCLC.

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