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.

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 The SARS-CoV-2 Host Cell Membrane Fusion Protein TMPRSS2 is A Tumor Suppressor and its Downregulation Promotes Antitumor Immunity and Immunotherapy Response in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Zhixian Liu ◽  
Zhilan Zhang ◽  
Qiushi Feng ◽  
Xiao-Sheng Wang
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Lung Adenocarcinoma ◽  
Tumor Progression ◽  
Antitumor Immunity ◽  
Host Cells ◽  
Host Cell Membrane ◽  
Clinical Prognosis ◽  
In Vivo Experiments

Abstract TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains unexplored. In five lung adenocarcinoma (LUAD) genomics datasets, we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, and clinical prognosis in LUAD by the bioinformatics approach. We found that TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD dataset we collected. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. In conclusion, TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a link between lung cancer and pneumonia caused by SARS-CoV-2 infection.

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.

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.

Epitope mapping of epidermal growth factor receptor (EGFR) in lung cancer using immunohistochemistry: Fine tuning the protocols

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21162-21162
Author(s):  
J. TIMAR ◽  
K. Derecskei ◽  
B. Dome ◽  
J. Moldvay
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Ligand Binding ◽  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Fine Tuning ◽  
Antigen Retrieval ◽  
Egfr Expression ◽  
Lung Adenocarcinomas ◽  
Cancer Tissues

21162 Background: Until now, immunohistochemistry was not able to become a reliable diagnostic approach for EGFR targeted therapies. The golden standard of the determination of EGFR protein expression in paraffin embedded cancer tissues is the EGFRpharmDXtm kit. Methods: Here we show data based on analysis of 110 lung adenocarcinomas, that the recommended protocol may not be optimal for ideal performance of the immunodetection, since microwave retrieval, extended primary antibody-incubation time and replacement of the developer reagent converted four EGFR-negative tumor into EGFR protein positive out of eight lung adenocarcinoma cases. Protocol modification improved the performance of another widely used EGFR-kit, Ventana's CONFIRM, where replacement of the protease antigen retrieval with microwave cooking converted several EGFR-negative tumors to strongly positive. Meanwhile both EGFR-kits detect EGFR expression (juxtamembrane domain) but do not provide information on the expression of epitopes critical from the point of view of targeted therapy. Results: We have developed two protocols, which can detect the ligand-binding (AB-10, BioMarkers) and C-terminal (AB- 335, Biogenex) cytoplasmic domains of the EGFR protein in paraffin embedded lung cancer tissues. We have shown, based on the analysis of more than 110 lung adenocarcinoma tissues, that the ligand binding domain of EGFR is rarely expressed while the C-terminal domain is ubiquitously expressed in EGFR-PharmDX and CONFIRM-positive cancers. The biological activity of EGFR can be characterized either by autophosphorylation of the receptor or by detection of divers phosphorylated downstream signaling components. We have found that unlike p1086 (detected by a Zymed antibody), the p1173 site of EGFR (identified by a rabbit monoclonal of Epitomics) can be detected 27/110 paraffin embedded lung adenocarcinomas. Conclusions: Using the tested antibody panel we can reliably determine the EGFR protein expression in paraffin embedded (lung)cancer tissues. This work was supported by Ministry of Education (NKFP1a-0024–05). No significant financial relationships to disclose.

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