scholarly journals Circulating Tumor Cell Methylation Profiles Reveal the Classification and Evolution of Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Small Cell ◽  
Whole Genome ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract Backgrounds: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: we first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: the bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusion: thus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

scholarly journals Circulating tumor cell methylation profiles reveal the classification and evolution of non-small cell lung cancer

2021 ◽  
Author(s):  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Small Cell ◽  
Whole Genome ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract BackgroundsThe ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers.Methodswe first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients.Resultsthe bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusionthus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

scholarly journals LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival

2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Methylation ◽  
Poor Survival ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract Background: LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods: Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detect the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 and miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results: We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions: SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.

scholarly journals LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival

2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Methylation ◽  
Poor Survival ◽  
Tumor Tissues ◽  
Nsclc Patients

Abstract Background: LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods: Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detected the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 or miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results: We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions: SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.

Single center, open and prospective evaluation of genomic sequencing on cerebro-spinal fluid, brain metastatic lesions and plasma from patients in non-small cell lung cancer with brain metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13578-e13578
Author(s):  
Chunhua Ma ◽  
Chuoji Huang ◽  
Zhi Li ◽  
Rong Jiang ◽  
Juncheng Zhang
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Small Cell Lung Cancer ◽  
Primary Tumor ◽  
Brain Lesion ◽  
Gene Mutations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients

e13578 Background: Leptomeningeal metastases are observed in 9.4% non–small Cell Lung Cancer (NSCLC) patients with EGFR mutations. Depending on patient specific gene mutations, tumor cells may also have different proliferative activity, leading to differential metastatic potential. However, the clinical significance of observed gene mutation differences between CSF, plasma, primary pulmonary tumor and metastatic brain tumor samples remains unclear and should be further explored. Methods: From Apr. 2018 to Jan. 2019, plasma and CSF paired samples were drawn from consented NSCLC patients with diagnosed brain metastasis. Of these 21, brain lesion samples were obtained from 5 patients. All the samples were tested by next-generation sequencing. Patients were treated based on the detection results. Results: For this cohort, the detection rate of EGFR mutations in CSF cfDNA versus plasma cfDNA/CTC was 57.1% and 23.8% respectively (p < 0.05). For patients who had not received tyrosine kinase inhibitor (TKI) therapy, the CSF cfDNA EGFR mutation results were consistent with results for plasma, brain lesion and primary tumor samples. Conversely, for patients who had received TKI therapy, EGFR mutations detected in CSF were consistent with those from brain samples, but different from those observed in plasma or primary tumor samples. A high response rate (ORR, 70%; DCR, 90%) was observed in patients with EGFR positive detected in CSF after treatment with second orthird-generation TKI. Among the EGFR mutations detected in CSF, the EGFR uncommon mutation frequency was 58.3%(7/12), including G7I9A/L861Q/L703P/R776H/G575R/T790M 85.7% (6/7) of these occurred in LM patients. One patient who progressed from BM to LM had an uncommon mutation in the CSF sample. Among these five patients with EGFR G719A or L861Q positive and T790M negative, 4 patients had PR and 1 patient had SD after the second-generation TKI therapy. Conclusions: Differences in EGFR gene mutations were observed between CSF, plasma, primary pulmonary lesion and brain tissue samples in NSCLC patients with diagnosed brain metastasis after TKI therapy. The reasons for this discrepancy remain to be understood. Nevertheless, CSF may be a useful prognostic tool for patient monitoring and metastasis risk evaluation. The detection of uncommon EGFR mutations may increase the risk of LM in NSCLC patients. Clinical trial information: ChiCTR1800017499.

scholarly journals MeImmS: Predict Clinical Benefit of Anti-PD-1/PD-L1 Treatments Based on DNA Methylation in Non-small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Shipeng Shang ◽  
Xin Li ◽  
Yue Gao ◽  
Shuang Guo ◽  
Dailin Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Copy Number Loss ◽  
Small Cell Lung ◽  
Cpg Sites ◽  
Nsclc Patients

Immunotherapy has become an effective therapy for cancer treatment. However, the development of biomarkers to predict immunotherapy response still remains a challenge. We have developed the DNA Methylation Immune Score, named “MeImmS,” which can predict clinical benefits of non-small cell lung cancer (NSCLC) patients based on DNA methylation of 8 CpG sites. The 8 CpG sites regulate the expression of immune-related genes and MeImmS was related to immune-associated pathways, exhausted T cell markers and immune cells. Copy-number loss in 1p36.33 may affect the response of cancer patients to immunotherapy. In addition, SAA1, CXCL10, CCR5, CCL19, CXCL11, CXCL13, and CCL5 were found to be key immune regulatory genes in immunotherapy. Together, MeImmS discovered the heterogeneous of NSCLC patients and guided the immunotherapy of cancer patients in the future.

Analyses on expression of trimethylation of histone H3 at lysine 27 and DNA methylation at CCGG sites in smoking and nonsmoking non-small cell lung cancer patients and their clinical significance.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23179-e23179
Author(s):  
Xiaohui Chen ◽  
Yujie Deng ◽  
Kunshou Zhu ◽  
Takeshi Nagayasu ◽  
Dan Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Opposite Direction ◽  
Methylation Level ◽  
Smoking Status ◽  
Histone H3 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ezh2 Expression ◽  
Nsclc Patients

e23179 Background: Smoking usually leads to epigenetic alterations like DNA methylation and histone modifications. We analyzed the effect that smoking had on DNA methylation level at CCGG sites and expression of trimethylation of histone H3 lysine 27 (H3K27me3), enhancer of zeste homolog 2 (EZH2) and their interactions in non-small cell lung cancer (NSCLC) patients. Methods: 42 NSCLC patients, 22 adenocarcinomas and 20 squamous cell carcinomas were enrolled. Expression of H3K27me3, EZH2 and PCNA were immunohistochemically detected. Apoptotic index in NSCLC with different smoking status was evaluated via TUNEL method. DNA methylation at CCGG sites was evaluated by HELMET method. Their correlation with clinicopathological data were calculated in relation to different smoking status. Results: Compared to the nonsmokers, smoker NSCLC patients were found more often of lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and higher EZH2 expression, and lower apoptotic cell index ( P< 0.05). DNA methylation level at CCGG sites negatively correlated to the Binkman Index( P= 0.017). Further, trend of H3K27me3 and EZH2 expression was in the same direction in most smokers, while in nonsmokers, their expression trend was mostly in the opposite direction ( P= 0.015). Trend of PCNA and EZH2 expression was in the opposite direction in most smokers, while in nonsmokers, their expression trend was mostly in the same direction ( P= 0.048). In addition, trend of CCGG methylation ratio and immunohistochemical expression of H3K27me3 was in the same direction in most smokers, while in nonsmokers, the trend was mostly in the opposite direction ( P= 0.049). Conclusions: NSCLC patients of different smoking status exhibit completely different epigenetic characteristics, and DNA methylation at CCGG sites would probably determine the expression trend of H3K27me3, EZH2 and PCNA.

scholarly journals CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Man Zhang ◽  
Wei Yang ◽  
Peng Wang ◽  
Yu Deng ◽  
Yu-Ting Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Antitumor Immunity ◽  
Tumor Development ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Tissues ◽  
Nsclc Patients ◽  
Draining Lymph Nodes

AbstractThe efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL−G12D/+Tp53fl/fl (KP) and the KrasLSL−G12D/+Lkb1fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+ and CD4+ T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.

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