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

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.

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

BioMed Research International ◽

10.1155/2021/5561569 ◽

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.

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Genome-wide analysis of microRNA signature in lung adenocarcinoma with EGFR exon 19 deletion

10.1101/032367 ◽

2015 ◽

Author(s):

Lixia Ju ◽

Mingquan Han ◽

Xuefei Li ◽

Chao Zhao

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Genetic Alterations ◽

Egfr Mutations ◽

Wild Type ◽

Lung Cancer Patients ◽

Whole Genome Microarray ◽

Exon 19 Deletion ◽

The Difference ◽

Exon 19

AbstractPurposeThe findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and microRNAs can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer.Materials and methodsIn this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and its wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we have detected the microRNAs expression in serum of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type.ResultsThe expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type.ConclusionsIt is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 can be further explored for potential predictor and targeted biomarker when it is difficult to get the tumors.

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Faculty Opinions recommendation of A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725638359.793508418 ◽

2015 ◽

Author(s):

Alexandru Grigorescu

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Low Dose ◽

Phase Ii Trial ◽

Small Cell ◽

Egfr Mutations ◽

Small Cell Lung ◽

Multicentre Phase ◽

Lung Cancer Patients ◽

Oncology Research

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Prevalence of EGFR Mutations and Clinico-Pathological Characteristics of Chilean Lung Cancer Patients

Asian Pacific Journal of Cancer Prevention ◽

10.31557/apjcp.2019.20.1.1 ◽

2019 ◽

Vol 20 (1) ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Roger Gejman ◽

Sergio Gonzalez ◽

Matias Munoz Medel ◽

Bruno Nervi ◽

Cesar Sanchez ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Egfr Mutations ◽

Lung Cancer Patients ◽

Pathological Characteristics

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A Multi-Institutional Surveillance of Clinicopathological Features and Molecular Epidemiology of Egfr Mutations in Lung Cancer Patients Living with Human Immunodeficiency Virus Infection in Japan

Annals of Oncology ◽

10.1093/annonc/mdu357.11 ◽

2014 ◽

Vol 25 ◽

pp. iv545

Author(s):

Y. Okuma ◽

J. Tanuma ◽

H. Otera ◽

Y. Kojima ◽

M. Yotsumoto ◽

...

Keyword(s):

Lung Cancer ◽

Human Immunodeficiency Virus ◽

Virus Infection ◽

Human Immunodeficiency Virus Infection ◽

Molecular Epidemiology ◽

Cancer Patients ◽

Clinicopathological Features ◽

Egfr Mutations ◽

Lung Cancer Patients ◽

Immunodeficiency Virus

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

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02781-8 ◽

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.

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