Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation.

Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC.

[SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice].

Background: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex.

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC.

Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy.

TMB and TCR Are Correlated Indicators Predictive of the Efficacy of Neoadjuvant Chemotherapy in Breast Cancer.

Immune characteristics were reported correlated to benefit neoadjuvant chemotherapy (NAC) in breast cancer, yet integration of comprehensive genomic alterations and T-cell receptors (TCR) to predict efficacy of NAC needs further investigation. This study simultaneously analyzed TMB (Tumor Mutation Burden), TCRs, and TILs (tumor infiltrating lymphocyte) in breast cancers receiving NAC was conducted in a prospective cohort ( = 22). The next-generation sequencing technology-based analysis of genomic alterations and TCR repertoire in paired breast cancer samples before and after NAC was conducted in a prospective cohort ( = 22).

High SHP2 expression determines the efficacy of PD-1/PD-L1 inhibitors in advanced KRAS mutant non-small cell lung cancer.

Background: Src homology region 2 domain-containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non-small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME).

Methods: Sixty-one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled.

Comparative analysis of target gene exon sequencing by cognitive technology using a next generation sequencing platform in patients with lung cancer.

Next generation sequencing (NGS) technology is an increasingly important clinical tool for therapeutic decision-making. However, interpretation of NGS data presents challenges at the point of care, due to limitations in understanding the clinical importance of gene variants and efficiently translating results into actionable information for the clinician. The present study compared two approaches for annotating and reporting actionable genes and gene mutations from tumor samples: The traditional approach of manual curation, annotation and reporting using an experienced molecular tumor bioinformationist; and a cloud-based cognitive technology, with the goal to detect gene mutations of potential significance in Chinese patients with lung cancer.

Establishment and application of a method of next generation sequencing of 285 genes in lung cancer based on Ion-Proton platform.

Background: The development of "precision medicine" needs a novel genetic screening and diagnostic technique for clinical detection. This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through testing 285 genes by customized next generation sequencing (NGS) on Ion-Proton platform.

Methods: We reviewed the related literature and collected data of genomic alteration that occurred in lung cancer.

Low frequency of mutation of epidermal growth factor receptor (EGFR) and arrangement of anaplastic lymphoma kinase (ALK) in primary pulmonary lymphoepithelioma-like carcinoma.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated.

Method: We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from 1st January, 2008 to 30th December, 2018.

Relationship of circulating tumor cells and Epstein-Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients.

We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline.

Intratumoral heterogeneity of EGFR-activating mutations in advanced NSCLC patients at the single-cell level.

Background: Intratumoral epidermal growth factor receptor (EGFR) mutational heterogeneity is yet controversial in non-small cell lung cancer (NSCLC) patients. Single-cell analysis provides the genetic profile of single cancer cells and an in-depth understanding of the heterogeneity of a tumor.

Methods: Firstly, single H1975 cells harboring the EGFR L858R mutation were submitted to flow cytometry isolation, nested polymerase chain reaction (nested-PCR) amplification, and direct DNA sequencing to assess the feasibility of single-cell direct DNA sequencing.

Clinical Utility of Cerebrospinal Fluid Cell-Free DNA as Liquid Biopsy for Leptomeningeal Metastases in ALK-Rearranged NSCLC.

Introduction: Leptomeningeal metastases (LMs) indicated a poor prognosis in NSCLC. LMs were more frequent in driver gene-mutated patients, and cerebrospinal fluid (CSF) cell-free DNA has shown unique genetic profiles of LM in EGFR-mutated LM. However, studies in patients with ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC with LMs are scarce.

Crizotinib in advanced non-small-cell lung cancer with concomitant ALK rearrangement and c-Met overexpression.

Objective: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI). The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression.

Methods: Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH.

[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

Background: Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism.

Methods: A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method.

Stromal PD-L1-Positive Regulatory T cells and PD-1-Positive CD8-Positive T cells Define the Response of Different Subsets of Non-Small Cell Lung Cancer to PD-1/PD-L1 Blockade Immunotherapy.

Introduction: Inhibition of programmed cell death-1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) by using an immune checkpoint inhibitor has emerged as a promising immunotherapy for NSCLC. The correlation of PD-L1 expression in tumor cells with treatment outcomes has been reported in many pivotal trials; however, the relationship remains unclear. Here, we demonstrate that those patients with both high density of PD-1-positive CD8 and PD-L1-positive CD4-positive CD25-positive (PD-1 PD-L1) regulatory T cells (Tregs) have a better response to PD1/PD-L1 blockade.

Clinical characteristics and sequence complexity of anaplastic lymphoma kinase gene fusions in Chinese lung cancer patients.

Objectives: To investigate the clinical characteristics of anaplastic lymphoma kinase (ALK) rearrangements and sequence complexity of the ALK fusion gene in Chinese lung cancer patients.

Methods: We prospectively screened ALK rearrangements in 1474 lung cancer specimens, including 1387 cases of non-small cell lung cancer (NSCLC), 54 cases of small cell lung cancer (SCLC), and 33 cases of cancer with lung metastasis from other organs by both standard polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE)-coupled PCR. Fifteen cases of ALK-positive RACE-coupled PCR products were transformed into Escherichia coli for molecular cloning and sequenced for complexity analysis.

Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells.

Leptomeningeal metastases are more common in non-small cell lung cancer (NSCLC) with mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of leptomeningeal metastases. We compared the CellSearch Assay, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected leptomeningeal metastases.

Establishment of a Novel Method for Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Mutations in Lung Cancer.

Background: Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.

Methods: A review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer.

Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer.

Background: The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. Thus, c-Met status during EGFR-TKI therapy should receive much attention.

Results: Forty-nine patients were selected as training cohort and 52 cases as validation cohort.

Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations.

Introduction: Leptomeningeal metastases (LM) have increased in patients with NSCLC, and prognostic factors and outcomes for LM with EGFR gene mutations have not been well studied.

Methods: We retrospectively analyzed patients with lung cancer from January 2011 to June 2015 at our institute. Treatments and clinical outcomes of LM were reviewed.

Establishment and application of a multiplex genetic mutation-detection method of lung cancer based on MassARRAY platform.

Objective: This study aims to establish a method for highly parallel multiplexed detection of genetic mutations in Chinese lung cancer samples through Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on MassARRAY mass spectrometry platform.

Methods: We reviewed the related literature and data on lung cancer treatments. We also identified 99 mutation hot spots in 13 target genes closely related to the pathogenesis, drug resistance, and metastasis of lung cancer.

Polymorphism of rs9387478 correlates with overall survival in female nonsmoking patients with lung cancer.

Background: Our previous study identified rs9387478 as a new susceptibility locus associated with lung cancer in never-smoking women in Asia; however, the clinical and prognostic significance of this finding is not known.

Methods: We analyzed the relationship between the rs9387478 single nucleotide polymorphism and i) clinical parameters and ii) overall survival time in 505 female nonsmoking lung cancer patients, using the chi-square test and Kaplan-Meier analysis with the log-rank test, respectively. We further established the epidermal growth factor receptor (EGFR) mutation status and assessed its association with rs9387478 genotypes as well as the efficacy of EGFR tyrosine kinase inhibitors.

Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing.

Few effective therapies have been developed for the treatment of lung squamous cell carcinoma (SQCC), in part due to a lack of understanding regarding the mechanisms underlying the initiation and development of this disease. Whole transcriptome sequencing not only provides insight into the expression of all transcribed genes, but offers an efficient approach for identifying genetic variations, including gene fusions, mutations and alternative splicing. In this study, we performed whole transcriptome sequencing of 10 patients with stage IIIA lung SQCC, and discovered a large number of single nucleotide variants (SNVs; mean of 12.