scholarly journals LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Murong Zhou ◽  
Yi Kong ◽  
Xiaobin Wang ◽  
Wen Li ◽  
Si Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Transmembrane Protein ◽  
Specific Antigen ◽  
Diagnosis And Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lung Cancer Patients ◽  
Serum And Urine

Lung cancer has a higher incidence rate and mortality rate than all other cancers. Early diagnosis and treatment of lung cancer remain a major challenge, and the 5-year survival rate of its patients is only 15%. Basic and clinical research, especially the discovery of biomarkers, is crucial for improving the diagnosis and treatment of lung cancer patients. To identify novel biomarkers for lung cancer, we used the iTRAQ8-plex labeling technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the serum and urine of patients with different stages of lung adenocarcinoma and healthy individuals. A total of 441 proteins were identified in the serum, and 1,161 proteins were identified in the urine. The levels of elongation factor 1-alpha 2, proteasome subunit alpha type, and spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls. The levels of transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 decreased significantly in the serum of patients with metastases compared with those of nonmetastatic lung cancer patients. In the urine of stage III and IV lung cancer patients, the prostate-specific antigen and prostatic acid phosphatase decreased significantly, whereas neutrophil defensin 1 increased significantly. The results of LC-MS/MS were confirmed by enzyme-linked immunosorbent assay (ELISA) for transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 in the serum. These proteins may be a potential early diagnosis and metastasis biomarkers for lung adenocarcinoma. Furthermore, the relative content of these markers in the serum and urine could be used to determine the progression of lung adenocarcinoma and achieve accurate staging and diagnosis.

scholarly journals Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Deng Pan ◽  
Dapeng Zhou ◽  
Weijing Cai ◽  
Weibo Wu ◽  
Wen Ling Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Chinese Population ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Lung Cancer Patients ◽  
Hla Class I Molecules

Abstract Background Mutant peptides presented by cancer cells are superior vaccine candidates than self peptides. The efficacy of mutant K-Ras, P53 and EGFR (Epidermal Growth Factor Receptor) peptides have been tested as cancer vaccines in pancreatic, colorectal, and lung cancers. The immunogenicity of EGFR Del19 mutations, frequent in Chinese lung adenocarcinoma patients, remains unclear. Results We predicted the HLA binding epitopes of Del19 mutations of EGFR in Chinese lung adenocarcinoma patients with NetMHC software. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the EGFR-reactive IgG in lung cancer patients. Del19 mutations may be presented by multiple HLA Class I molecules, with delE746_A750 presented by 37.5% of Chinese population. For HLA Class II molecules, Del19 mutations of EGFR may be presented by multiple HLA-DRB1 molecules, with delE746_A750 presented by 58.1% of Chinese population. Serum reactivity to wild type EGFR protein was significantly higher in patients with Del19 EGFR mutations than those with EGFR L858R point mutation or with EGFR wild type genotype. Conclusions These findings suggest that Del19 mutations of EGFR, with an estimated frequency of 40% in Chinese lung adenocarcinoma patients, may serve as unique targets for immunotherapy in Chinese lung cancer patients.

scholarly journals Aberrant Fucosylation of Saliva Glycoprotein Defining Lung Adenocarcinomas Malignancy

2021 ◽  
Author(s):  
Shuang Yang ◽  
Ziyuan Gao ◽  
Zhen Wu ◽  
Ying Han ◽  
Xumin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Solid Phase ◽  
Clinical Specimens ◽  
Aberrant Glycosylation ◽  
Lung Adenocarcinomas ◽  
Core Fucosylation

Aberrant glycosylation is a hallmark of cancer found during tumorigenesis and tumor progression. Lung cancer induced by oncogene mutations has been detected in the patient's saliva, and saliva glycosylation has been altered. Saliva contains highly glycosylated glycoproteins, the characteristics of which may be related to various diseases. Therefore, elucidating cancer-specific glycosylation in the saliva of healthy, non-cancer, and cancer patients can reveal whether tumor glycosylation has unique characteristics for early diagnosis. In this work, we used a solid-phase chemoenzymatic method to study the glycosylation of saliva glycoproteins in clinical specimens. The results showed that the alpha1,6-core fucosylation of glycoproteins in cancer patients was significant increased. The fucosylation of alpha1,2 or alpha1,3 is also increased in cancer patients. We further analyzed the expression of fucosyltransferases responsible for alpha1,2, alpha1,3, alpha1,6 fucosylation. The fucosylation of the saliva of cancer patients is drastically different from that of non-cancer or health controls. These results indicate that the glycoform of saliva fucosylation distinguishes lung cancer from other diseases, and this feature has the potential to diagnose lung adenocarcinoma.

Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-stage Lung Cancer Diagnosis

2020 ◽  
Author(s):  
Lingling Wan ◽  
Yutong He ◽  
Qingyi Liu ◽  
Di Liang ◽  
Yongdong Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Diagnosis ◽  
Cancer Patients ◽  
Early Stage ◽  
Untargeted Metabolomics ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Patients ◽  
Diagnosis Of Lung Cancer ◽  
Metabolomics Analysis ◽  
Stage Lung Cancer

Abstract Background: Lung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis. Methods: In this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients, and the early diagnostic value of these assays in lung cancer was analyzed. Results: 62.5% (30/48) of lung cancer patients had ≥ 1 CTC. By CTC NGS, we found that > 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC > 0.9). Conclusions: Our results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer. This possibility requires more in-depth large-sample research for verification.

The pathway to diagnosis and treatment for surgically managed lung cancer patients

2019 ◽  
Author(s):  
Victoria White ◽  
Rebecca J Bergin ◽  
Robert J Thomas ◽  
Kathryn Whitfield ◽  
David Weller
Keyword(s):  
Lung Cancer ◽  
Primary Care ◽  
Cancer Patients ◽  
Secondary Care ◽  
Primary Care Physicians ◽  
Treatment Time ◽  
Early Stage ◽  
Diagnosis And Treatment ◽  
Early Stage Disease ◽  
Lung Cancer Patients

Abstract Background Most lung cancer is diagnosed at an advanced stage, resulting in poor survival. This study examined diagnostic pathways for patients with operable lung cancer to identify factors contributing to early diagnosis. Methods Surgically treated lung cancer patients (aged ≥40, within 6 months of diagnosis), approached via the population-based Cancer Registry, with their primary care physicians (PCPs) and specialists completed cross-sectional surveys assessing symptoms, diagnostic route (symptomatic or ‘investigation’ of other problem), tests, key event dates and treatment. Time intervals to diagnosis and treatment were determined, and quantile regression examined differences between the two diagnostic routes. Cox proportional hazard regression analyses examined associations between survival and diagnostic route adjusting for stage, sex and age. Results One hundred and ninety-two patients (36% response rate), 107 PCPs and 55 specialists participated. Fifty-eight per cent of patients had a symptomatic diagnostic route reporting an average of 1.6 symptoms, most commonly cough, fatigue or haemoptysis. Symptomatic patients had longer median primary care interval than ‘investigation’ patients (12 versus 9 days, P < 0.05) and were more likely to report their PCP first-ordered imaging tests. Secondary care interval was shorter for symptomatic (median = 43 days) than investigation (median = 62 days, P < 0.05) patients. However, 56% of all patients waited longer than national recommendations (6 weeks). While survival estimates were better for investigation than symptomatic patients, these differences were not significant. Conclusion Many operable lung cancer patients are diagnosed incidentally, highlighting the difficulty of symptom-based approaches to diagnosing early stage disease. Longer than recommended secondary care interval suggests the need for improvements in care pathways.

scholarly journals The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer

2020 ◽  
Author(s):  
Ming-Fang Wu ◽  
Chih-An Lin ◽  
Tzu-Hang Yuan ◽  
Hsiang-Yuan Yeh ◽  
Sheng-Fang Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Malignant Pleural Effusion ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Anti Cancer ◽  
Cancer Activity

Abstract Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. Conclusions We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

scholarly journals Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

2020 ◽  
Vol 13 (2) ◽  
pp. 896-903
Author(s):  
Brendan Seng Hup Chia ◽  
Wen Long Nei ◽  
Sabanayagam Charumathi ◽  
Kam Weng Fong ◽  
Min-Han Tan
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Disease ◽  
Lung Cancer Patients ◽  
Limited Stage ◽  
Potential Biomarker ◽  
Egfr Mutant

The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13.5 months, an association between a detectable pre-radiotherapy plasma EGFR ctDNA and early tumour relapse (155 days vs. NR, p = 0.004) was noted. One patient with persistent plasma EGFR ctDNA predated radiological progression. The role of ctDNA in early-stage lung cancer is developing. Plasma EGFR ctDNA could be a useful biomarker in lung cancer patients undergoing radical treatments for staging, prognostication, and follow-up. These preliminary findings should be explored in larger studies.

Correlation of levels of extracellular vesicles in peripheral and pulmonary blood plasma with pathological stages of lung cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15558-e15558
Author(s):  
Hyun Koo Kim ◽  
Byeong Hyeon Choi ◽  
Yu Hua Quan ◽  
Jiyun Rho ◽  
Sunghoi Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Human Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Peripheral Vein ◽  
Healthy Human ◽  
Lung Cancer Patients ◽  
Pathological Stages

e15558 Background: Exosome concentration is known to be higher in cancer patients than in healthy individuals. In this study, we observed that the levels of exosomes differ in tumor-draining pulmonary blood and in peripheral blood in animal models and human subjects at different pathological stages of lung cancer. Methods: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from a peripheral vein in all groups, and pulmonary blood was collected intraoperatively from all groups, except the healthy human controls. Quantitative analysis of exosomes was performed by nanoparticle tracking assay, CD63 enzyme-linked immunosorbent assay, and western blotting. Results: The peripheral blood of lung cancer-bearing animals and patients with lung cancer carried higher amounts of exosome than that from healthy controls ( p < 0.01 and p < 0.001, respectively). Moreover, pulmonary blood from lung cancer-bearing animals and patients had significantly higher exosome levels, compared to preoperative peripheral blood ( p < 0.01 and p < 0.0001, respectively). In patients, pulmonary exosome levels showed higher correlation with pathological stages of lung cancer than the peripheral exosome levels. Conclusions: Exosome levels increased with increasing grade of lung cancer, and this trend was more prominent in the pulmonary than in the peripheral blood.

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