Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients

Zhang, Xuchao; Wang, Jun; Shao, Guoguang; Wang, Qun; Qu, Xiaotao; Wang, Bo; Moy, Christopher; Fan, Yue; Albertyn, Zayed; Huang, Xiaokun; Zhang, Jingyu; Qiu, Yang; Platero, Suso; Lorenzi, Matthew V.; Zudaire, Enrique; Yang, Jennifer; Cheng, Ying; Xu, Lin; Wu, Yi‐Long

doi:10.1038/s41467-019-09762-1

Cited by 153 publications

(155 citation statements)

References 58 publications

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“…The most common variants detected in patients with AC were in EGFR and KRAS genes. The two most commonly detected variants were also seen in patients with SCC in a diverse frequency according to their ethnic origin [19]. In the present study, EGFR and MET variants were also observed in patients with SCC.…”

Section: Discussionsupporting

confidence: 70%

Results of liquid biopsy studies by next generation sequencing in patients with advanced stage non-small cell lung cancer: Single center experience from Turkey

Büyükşimşek

Toğun

Oguz

et al. 2019

Balkan Journal of Medical Genetics

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Several studies demonstrated the utility of plasma-based cell-free circulating tumor DNA (ccfDNA) in determination of mutations in non-small cell lung cancer (NSCLC). We aimed to report our results of next generation sequencing (NGS) using liquid biopsy in patients with NSCLC. Patients with advanced stage NSCLC were enrolled and their genomic profiling results were recorded. Next generation sequencing targeted panel includes 19 hot-spot genes. The plasma was separated from the peripheral blood sample and ccfDNAs were isolated for NGS. We performed genomic profiling in 100 patients (20 females and 80 males) with a median age of 59.3 (range 26-79). A second liquid biopsy was performed in eight patients who developed progressive disease after the first treatment. The study population had adenocarcinoma (AC) (n = 73), squamous cell carcinoma (SCC) (n = 14), or NSCLC-NOS (not otherwise specified) (n = 13). In the SCC group, three of 14 patients had variants on EGFR and MET genes. In the AC and NSCLC-NOS groups, 39 out of 86 patients (45.3%) had variants. The most common one was in the EGFR gene (n = 27, 31.4%) including seven mutations related to drug resistance and two were polymorphisms. Three patients had both driver and resistance mutations (EGFR T790M, n = 2; KRAS exon 2 G12S and MET exon 14 E1012K, n = 1). Fifteen patients (17.4%) had an activating EGFR mutation and eight patients (9.3%) had variants in the KRAS gene. We reported our results regarding genomic profiling related to treatment using liquid biopsy in patients with NSCLC. Advantages of this method are the non invasiveness and reproducibility.

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Section: Discussionsupporting

confidence: 70%

Results of liquid biopsy studies by next generation sequencing in patients with advanced stage non-small cell lung cancer: Single center experience from Turkey

Büyükşimşek

Toğun

Oguz

et al. 2019

Balkan Journal of Medical Genetics

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“…It has been reported that the genomic features of lung cancer were associated with in ammatory tumorin ltrating lymphocytes [18]. For example, the in ltrating B lymphocyte abundance was higher in the EGFR-mutated patients [19].…”

Section: Introductionmentioning

confidence: 97%

The Relationship Between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study

Dai

Ren

et al. 2020

Preprint

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Abstract Background It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer. Methods 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8 + T lymphocytes and the rate of CD4/CD8. Results Patients with EGFR mutation has lower percentage of CD8 + lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P = 0.041). Patients with high CD3 + had better OS than those with low (27 versus 14 months, P = 0.002). OS of higher CD4 + and CD4/CD8 rate had longer OS than of lower (27 versus 12 months, P = 0.002; 25 versus 9 months, P = 0.008, respectively). Patients with high CD8 + had poor PFS than low group (6 versus 11 months, P = 0.009). There was a negative correlation between CD3 + and CD4 + cells and OS in smoking stage 2 female lung cancer patients (PCC = 0.626, P < 0.05; PCC = 0.534, P < 0.05, respectively). In stage 1 male lung cancer patients, CD8 + T cell is negatively correlated with OS and PFS (PCC = 0.295, P < 0.05; PCC = 0.280, P < 0.05, respectively) Conclusions Lung cancer patients with EGFR mutation had lower percentage of CD8 + lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.

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“…Lung squamous cell carcinoma (LSCC) accounts for approximately 25-30% of all cases of nonsmall cell lung cancer (NSCLC) with more than 70% patients diagnosed in advanced stage [1,2] and causes approximately 400,000 deaths per year worldwide [3]. Currently, surgery, radiation, and chemotherapy are still its main treatment.…”

Section: Introductionmentioning

confidence: 99%

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Chen²,

Zhuang

et al. 2020

EPMA Journal

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Background Ubiquitination is an important molecular event in lung squamous cell carcinoma (LSCC), which currently is mainly studied in nonsmall cell lung carcinoma cell models but lacking of ubiquitination studies on LSCC tissues. Here, we presented the ubiquitinated protein profiles of LSCC tissues to explore ubiquitination-involved molecular network alterations and identify abnormally ubiquitinated proteins as useful biomarkers for predictive, preventive, and personalized medicine (PPPM) in LSCC. Methods Anti-ubiquitin antibody-based enrichment coupled with LC-MS/MS was used to identify differentially ubiquitinated proteins (DUPs) between LSCC and control tissues, followed by integrative omics analyses to identify abnormally ubiquitinated protein biomarkers for LSCC. Results Totally, 400 DUPs with 654 ubiquitination sites were identified,, and motifs AX (1/2/3)-K* were prone to be ubiquitinated in LSCC tissues. Those DUPs were involved in multiple molecular network systems, including the ubiquitinproteasome system (UPS), cell metabolism, cell adhesion, and signal transduction. Totally, 44 hub molecules were revealed by protein-protein interaction network analysis, followed by survival analysis in TCGA database (494 LSCC patients and 20,530 genes) to obtain 18 prognosis-related mRNAs, of which the highly expressed mRNAs VIM and IGF1R were correlated with poorer prognosis, while the highly expressed mRNA ABCC1 was correlated with better prognosis. VIM-encoded protein vimentin and ABCC1-encoded protein MRP1 were increased in LSCC, which were all associated with poor prognosis. Proteasome-inhibited experiments demonstrated that vimentin and MRP1 were degraded through UPS. Quantitative ubiquitinomics found ubiquitination level was decreased in vimentin and increased in MRP1 in LSCC. These findings showed that the increased vimentin in LSCC might be derived from its decreased ubiquitination level and that the increased MRP1 in LSCC might be derived from its protein synthesis > degradation. GSEA and co-expression gene analyses revealed that VIM and Electronic supplementary material The online version of this article (

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Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients

Cited by 153 publications

References 58 publications

Results of liquid biopsy studies by next generation sequencing in patients with advanced stage non-small cell lung cancer: Single center experience from Turkey

Results of liquid biopsy studies by next generation sequencing in patients with advanced stage non-small cell lung cancer: Single center experience from Turkey

The Relationship Between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

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