microdroplet-digital-polymerase-chain-reaction-for-precision

Microdroplet Digital Polymerase Chain Reaction for Precision Detection of Non-Small Cell Lung Cancer Mutations

On a global scale, lung cancer continues to be the primary contributor to cancer-related deaths, with its prevalence ranking second only to that of kidney ...

First Affiliated Hospital of Kunming Medical University

The molecular mechanisms involved in small-cell lung cancer (SCLC) are largely unknown. Recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a critical role.

Identification of alternative splicing and lncRNA genes in pathogenesis of small cell lung cancer based on their RNA sequencing.

 For lobectomy in non-small cell lung cancer (NSCLC), whether interrupting the pulmonary vein first (Vein-first) achieves better perioperative and survival outcomes than interrupting the pulmonary artery first (Artery-first) remains controversial. We conducted this meta-analysis to compare outcomes between the two groups to facilitate better surgical decision-making.  Web of Science, EMBASE, Cochrane Library, Ovid MEDLINE, PubMed, ScienceDirect, and Scopus were searched for eligible studies comparing Vein-first and Artery-first procedures. The primary endpoints were survival indicators [overall survival (OS), disease-free survival (DFS), and lung cancer-specific survival (LCSS)]. Secondary endpoints included intraoperative indicators, hospitalization, and follow-up indicators.  After screening 2,505 studies, 8 studies involving 1,714 patients (Vein-First group: 881 patients; Artery-first group: 833 patients) were included. The vein-first group achieved better OS [HR (hazard ratio): 1.46, 95% confidence interval (CI): 1.12-1.91,  = 0.005], DFS (HR: 1.60, 95% CI: 1.23-2.08,  < 0.001), and LCSS (HR: 1.64, 95% CI: 1.16-2.31,  = 0.005). The survival rates of OS at 2-5 years, DFS at 1-5 years, and LCSS at 3-5 years were also higher in the Vein-First group. Subgroup analyses suggested that the advantages of survival in the Vein-First group were primarily embodied in the subgroups of squamous cell carcinoma (SCC) and earlier pathological TNM stage (I-II). Operative time, intraoperative blood loss, total complications, and total recurrences were comparable between the two groups.  The Vein-first sequence is the suitable choice of vessel interruption sequence during lobectomy for NSCLC with better survival and similar perioperative outcomes, especially for stage I-II SCC.

Effects of Vessel Interruption Sequence During Lobectomy for Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Epidermal growth factor receptor (EGFR) and BRAF are 2 driver genes in non-small cell lung cancer (NSCLC) which are normally mutually exclusive. It has been previously reported that the existence of BRAF V600E in EGFR-mutated NSCLC patients could cause resistance to EGFR tyrosine kinase inhibitors (TKIs), but the influence of other BRAF actionable mutations on resistance to EGFR-TKIs has not yet been investigated. Understanding the coexistence of EGFR and BRAF actionable mutations in Chinese NSCLC patients may be essential for further treatment and prognostic prediction.

Co-mutations of epidermal growth factor receptor and BRAF in Chinese non-small cell lung cancer patients.

Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of precision medicine.

Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing.

Emerging evidence has underscored infiltrating immune cells in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Owing to screening programs, the prevalence of early-stage NSCLC is growing, but its high recurrence risk and poor survival impose an increasing demand for further understanding the TME.

Multidimensional profiling depicts infiltrating immune cell heterogeneity in the tumor microenvironment of stage IA non-small cell lung cancer.

Anaplastic lymphoma kinase (ALK) fusion was found in 3-7% of all patients with nonsmall cell lung cancer. The efficacy of ALK-tyrosine kinase inhibitor (ALK-TKI) in EML4-ALK has been extensively studied, whereas little evidence is available on its efficacy in rare ALK fusions. Here, we report the performance of crizotinib in a 50-year-old male lung adenocarcinoma patient with a novel rare SEC31A-ALK fusion. Computed tomography (CT) scan revealed multiple patchy high-density shadows in both lungs. The larger ones are located near the spine in the right lung lower lobe (55 × 34 mm) and the left hilar region (45 × 26 mm), with multiple enlarged mediastinal and axillary lymph nodes. Biopsy by bronchoscopy revealed invasive adenocarcinoma. The pathological stage of T4N3M1b (clinical stage: IVA) was confirmed. Next-generation sequencing revealed SEC31A: exon20~ALK: exon20 fusion, ABCB1 amplification, FGF19 amplification, DAXX p.S213L, MUTYH p.R19*(germline mutation and pathogenic) with tumor mutational burden at 3.2 mutations/Mb, microsatellite stable, proficient mismatch repair and PD-L1 positive [immunohistochemistry, tumor proportion score(TPS) 1-49% (TPS = 25%)]. Based on these findings, crizotinib was recommended for the first-line treatment at 250 mg twice daily. The first CT assessment after 2-month therapy showed partial response (PR) for the two larger lesions, multiple shadows and nodules in both lungs and the mediastinal and axillary lymph nodes. Crizotinib at 250 mg twice a day was applied in the following 9 months. Assessment at every 3 months (up to 1-year after diagnosis) showed further absorption for all lesions (continuous PR). We reported a novel rare ALK fusion SEC31A: EXON20~ALK: exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.

First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma: a case report and literature reviews.

Article	Year
Identification of alternative splicing and lncRNA genes in pathogenesis of small cell lung cancer based on their RNA sequencing. Advances in clinical and experimental medicine : official organ Wroclaw Medical University\| PubMed ID: 31403267	2019
Effects of Vessel Interruption Sequence During Lobectomy for Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Frontiers in surgery\| PubMed ID: 34381809	2021
Co-mutations of epidermal growth factor receptor and BRAF in Chinese non-small cell lung cancer patients. Annals of translational medicine\| PubMed ID: 34532458	2021
Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing. Neoplasia (New York, N.Y.)\| PubMed ID: 34735995	2021
Multidimensional profiling depicts infiltrating immune cell heterogeneity in the tumor microenvironment of stage IA non-small cell lung cancer. Thoracic cancer\| PubMed ID: 35150094	2022
First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma: a case report and literature reviews. Anti-cancer drugs\| PubMed ID: 36730620	2023

Guoli Lv

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