Detection and verification of coexisting diagnostic markers in plasma and serum of patients with non-small-cell lung cancer

2021 ◽  
Author(s):  
Mengjie Yu ◽  
Runbin Sun ◽  
Yuqing Zhao ◽  
Feng Shao ◽  
Wei Zhu ◽  
...  

Aim: To screen and identify the potential biomarkers co-existing in plasma and serum of patients with non-small-cell lung cancer (NSCLC), and establish appropriate diagnostic models. Methods: A cohort of 195 plasma samples and 180 serum samples were obtained from healthy controls (HC), adenocarcinoma (AdC) and squamous cell carcinoma (SqCC) patients enrolled from the First Affiliated Hospital of Nanjing Medical University. Metabolites in plasma and serum were analyzed by GC-MS. Results: Hypoxanthine was found to have good performance in the differential diagnosis of NSCLC (including AdC and SqCC) and HC (area under the receiver operating characteristic [AUROC] ≥0.85). Combinations of metabolites could be used for differential diagnosis of NSCLC and HC (AUROC >0.93), AdC and HC (AUROC >0.91), SqCC and HC (AUROC >0.95), AdC and SqCC (AUROC >0.72). Conclusions: Metabolomics based on GC-MS can screen and identify the differential metabolites coexisting in plasma and serum of patients with NSCLC, and prediction models established by this method can be used for the differential diagnosis of patients with NSCLC.

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3012
Author(s):  
Naseer Ahmed ◽  
Biniam Kidane ◽  
Le Wang ◽  
Zoann Nugent ◽  
Nataliya Moldovan ◽  
...  

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.


Author(s):  
Thang Thanh Phan ◽  
Bich‐Thu Tran ◽  
Son Truong Nguyen ◽  
Toan Trong Ho ◽  
Hang Thuy Nguyen ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshihisa Shimada ◽  
Jun Matsubayashi ◽  
Yujin Kudo ◽  
Sachio Maehara ◽  
Susumu Takeuchi ◽  
...  

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.


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 ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22062-e22062
Author(s):  
Vy Thuy Dinh ◽  
Medhi Wangpaichitr ◽  
Dao M. Nguyen ◽  
Maria Matsangou ◽  
Chunjing Wu ◽  
...  

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.


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