scholarly journals The isocitrate dehydrogenase 1 is a potential prognostic indicator for non-small cell lung cancer patients

2021 ◽  
pp. 172460082110525
Author(s):  
Xintong Zhang ◽  
Shang Ma ◽  
Yan Chen ◽  
Yanjun Yin ◽  
Wanqiu Bai ◽  
...  

Background The serum isocitrate dehydrogenase 1(IDH1) level is significantly elevated in patients with non-small cell lung cancer (NSCLC) and has important clinical value as a marker for early diagnosis. This study examined the dynamic changes of serum IDH1 levels of patients with NSCLC undergoing surgery or medical treatment, to evaluate its potential prognostic value. Methods The study cohort included 83 NSCLC patients who underwent surgery, 37 NSCLC patients who underwent medical treatment, 50 healthy controls, and 52 disease controls. Serum levels of IDH1 were assayed by enzyme-linked immunoassay. Tumor biomarkers including carcinoembryonic antigen, squamous cell carcinoma, neuron-specific enolase, CYFRA21-1, and pro-gastrin-releasing peptide—which are currently used in clinical practice—were measured by automatic immunoanalyzers. Results Serum IDH1 was significantly higher in patients with NSCLC compared with healthy people or patients with benign lung diseases ( p < 0.001). The area under the receiver operating characteristic curve for diagnosis and differential diagnosis were 0.897 and 0.879, respectively, which were superior to the five tumor markers. Serum IDH1 levels decreased in most patients after surgery, with the most dramatic changes in patients with stage I tumors compared with stage II and III. Analyses of changes in the serum IDH1 level of patients after receiving chemotherapy or targeted therapy revealed that for patients with progressive disease, serum IDH1 increased significantly after treatment; for patients with partial response or stable disease, it decreased steadily. Conclusion IDH1 has potential prognostic value and may be used as a marker for the monitoring of treatment efficacy.

2007 ◽  
Vol 2 (8) ◽  
pp. S528-S529
Author(s):  
Rafael Sirera ◽  
Carlos Camps ◽  
José-Luis González-Larriba ◽  
Juan Lao ◽  
R García-Gómez ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20592-e20592
Author(s):  
Mary J. Fidler ◽  
Marta Batus ◽  
Imad Tarhoni ◽  
Selina Sayidine ◽  
Cristina L. Fhied ◽  
...  

e20592 Background: Current evaluation of immunohistochemical expression of PDL-1 (program death receptor 1 ligand) can select some non-small cell lung cancer (NSCLC) patients who may benefit from anti-PD1 directed therapy. It is an imperfect marker and there is little information about systemic modulation of the immune system on therapy. In this study we explored the prognostic value of baseline circulating immune checkpoint and inflammatory molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD1 therapy. Methods: Prospectively collected serum from advanced NSCLC patients receiving nivolumab or pembrolizumab were evaluated with the MILLIPLEX Human High Sensitivity T-cell (17-plex) and ProcartaPlex Human Immuno-Oncology Checkpoint (14-plex) panels on our Luminex FlexMAP 3D. Biomarker level cutoffs were optimized and evaluated against progression-free survival (PFS) and overall survival (OS) using log-rank analysis. Results: 21 cases were enrolled in this pilot study: 72% Caucasian, 61% female, 24% never-smokers. IL-10 was found to have a significant association with both PFS (p = 0.0055) and OS (p = 0.024), with levels below 3.32 pg/mL being associated with a superior clinical outcome. We also found IL-2 and IL-6 to have significant associations with PFS (p = 0.033 and 0.040, respectively), again, with low levels being associated with a superior outcome. Neither of these had significant associations with OS. Low circulating levels of the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) protein were associated with superior PFS (p = 0.036), and a weak trend (p = 0.19) for OS. Conclusions: In this small exploratory pilot study we identified several circulating molecules associated with inflammation and immune system regulation that may have prognostic value for anti-PD-1 therapy. Notably, TIM-3 is a Th1-specific protein associated with macrophage activation and is also a component of T-cell exhaustion along with LAG3 and PD-1. Additional studies to follow up on these findings in larger cohorts are underway.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ying Liu ◽  
Jian Cui ◽  
Yun-Liang Tang ◽  
Liang Huang ◽  
Cong-Yang Zhou ◽  
...  

The S100 protein family is involved in cancer cell invasion and metastasis, but its prognostic value in non-small-cell lung cancer (NSCLC) has not been elucidated. In the present study we investigated the prognostic role of mRNA expression of each individual S100 in NSCLC patients through the Kaplan–Meier plotter (KM plotter) database. Expression of 14 members of the S100 family correlated with overall survival (OS) for all NSCLC patients; 18 members were associated with OS in adenocarcinoma, but none were associated with OS in squamous cell carcinoma. In particular, high mRNA expression level of S100B was associated with better OS in NSCLC patients. The prognostic value of S100 according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of NSCLC was further assessed. Although the results should be further verified in clinical trials our findings provide new insights into the prognostic roles of S100 proteins in NSCLC and might promote development of S100-targeted inhibitors for the treatment of NSCLC.


2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. A31-A31
Author(s):  
Wouter W. Mellema ◽  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Daniëlle A.M. Heideman ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Yang ◽  
Yu Chong ◽  
Mengyuan Chen ◽  
Wumin Dai ◽  
Xia Zhou ◽  
...  

Abstract Background Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. Methods LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan–Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. Results Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. Conclusions Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.


2021 ◽  
Author(s):  
Yang Yang ◽  
Yu Chong ◽  
Mengyuan Chen ◽  
Wumin Dai ◽  
Xia Zhou ◽  
...  

Abstract BackgroundLDHA is overexpressed in many kinds of cancer, and associated with poor prognosis. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC.MethodsLDHA mRNA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan-Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and autophagy was examined by monodansylcadaverin (MDC) staining.ResultsBoth mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity.ConclusionsOur study suggests inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.


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