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

Lung cancer may be a result of complex factors. Small mineral particle is the well-known inducer of lung cancer. Previous study revealed the high morbidity of lung cancer in Xuan Wei in China, and the main cause of lung cancer is the use of smoky coal there. And it is generally accepted that chronic inflammation induced by small mineral particle may be a cause of lung cancer. But the relationship between chronic lung inflammation and lung cancer is largely unknown. In the present study, we found that silica particle was able to induce the secretion of interleukin-1β from a Xuan Wei lung cancer cell line, XWLC-05. At the same time, microRNA-101 (mir-101) was found to be downregulated by the treatment of silica particle. Interestingly, the interleukin 1 receptor antagonist and interleukin-1β antibody can reduce silica particle-induced downregulation of mir-101. Twenty-four Xuan Wei lung tumor tissues were collected to detect the expression level of mir-101 and enhancer of zeste homolog 2 (EZH2), which is the potential target of mir-101. The results showed that mir-101 was down-regulated and EZH2 were upregulated. Subsequently, the roles of mir-101 and EZH2 in tumor growth and progression in vitro were tested. Overexpression of mir-101 mimics was able to suppress the expression of EZH2 in XWLC-05 cells. And this resulted in the inhibited tumor cell growth and attenuated cell migration. The results in the present study showed that particle can induce the secretion of interleukin-1β. Interleukin-1β subsequently induces the downregulation of mir-101, which may result in the upregulated level of EZH2, and occurrence of lung cancer. We for the first time proposed the role interleukin-1β-mir-101-EZH2 axes in the particle-induced lung cancer. Further study may be needed to decipher the detailed mechanism involved.

Interleukin-1β-mediated suppression of microRNA-101 and upregulation of enhancer of zeste homolog 2 is involved in particle-induced lung cancer.

Tumor spread through air spaces (STAS) as a new pathological invasion mode is closely related to many clinicopathological factors. In lung adenocarcinoma, micropapillary and solid pathological subtypes are most related; STAS for early stage lung adenocarcinoma, surgical type of lobectomy seems to benefit better than sublobar resection, which may up-regulate the pathological stage of early lung cancer; Moreover, STAS is closely related to squamous cell carcinoma and other non-small cell lung cancer (NSCLC). In addition, intraoperative frozen-section pathological detection of STAS is difficult and controversial. STAS as an independent risk factor for tumor recurrence is also an important factor indicating poor prognosis. This paper reviews the research status and progress of STAS. .

[Progress on the Study of Tumor Spread Through Air Spaces in the Clinicopathological Characteristics of Lung Adenocarcinoma and Its Influence on the Surgical Treatment and Prognosis of Lung Cancer].

Hepatoid adenocarcinoma (HAC) occurs in extrahepatic organs such as the gastrointestinal tract, testes, ovaries, lungs, mediastinum and pancreas, and frequently produces α-fetoprotein (AFP). HAC of the lung (HAL) is rare, characterized by difficult treatment and poor prognosis. There are no reports of HAL in Yunnan-Guizhou Plateau, China.

Primary hepatoid adenocarcinoma of the lung in Yungui Plateau, China: A case report.

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.

Xuanwei County in Southwest China shows the highest incidence and mortality rate of lung cancer in China. Although studies have reported distinct clinical characteristics of patients from Xuanwei, the molecular features of these patients with non-small cell lung cancer (NSCLC) remain unclear. Here, we comprehensively characterised such cases using next-generation sequencing (NGS). Formalin-fixed, paraffin-embedded tumour samples from 146 patients from Xuanwei with NSCLC were collected for an NGS-based target panel assay; their features were compared with those of reference Chinese and The Cancer Genome Atlas (TCGA) cohorts. Uncommon  mutations, defined as mutations other than L858R, exon 19del, exon 20ins, and T790M, were the predominant type of  mutations in the Xuanwei cohort. Patients harbouring uncommon  mutations were more likely to have a family history of cancer ( = 0.048). A higher frequency of  mutations and lower frequency of rearrangement alterations were observed in the Xuanwei cohort ( < 0.001). Patients from Xuanwei showed a significantly higher tumour mutation burden than the reference Chinese and TCGA cohorts ( < 0.001). Our data indicates that patients from Xuanwei with NSCLC harbouring G719X/S768I co-mutations may benefit from treatment with EGFR-tyrosine kinase inhibitors. Our comprehensive molecular profiling revealed unique genomic features of patients from Xuanwei with NSCLC, highlighting the potential for improvement in targeted therapy and immunotherapy.

Next-Generation Sequencing Reveals High Uncommon EGFR Mutations and Tumour Mutation Burden in a Subgroup of 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.

Based on data analysis of 9649 Chinese primary NSCLC patients, we calculated the exact proportion of EGFR subtypes in NSCLC and evaluated the TMB level, PD-L1 expression level and tumor immune microenvironment among different EGFR mutation subtypes. Postoperative follow-up data for 98 patients were collected and analyzed. The results showed that several uncommon EGFR mutation subtypes have a higher proportion of TMB-high or strong positive PD-L1 expression than the total EGFR mutation group. In addition, different subtypes have different characteristics related to the immune microenvironment, such as G719 mutations being associated with more CD8 T cell infiltration into tumors; except for EGFR 19del, CD8 T cell infiltration into tumors of other EGFR mutation subtypes were similar to that of wildtype EGFR. Moreover, follow-up results revealed that components of the immune microenvironment have prognostic value for NSCLC patients, with different prognostic biomarkers for NSCLC patients with and without EGFR mutations. These results suggest that patients with different EGFR mutations need to be treated differently. The prognosis of NSCLC patients may be assessed through components of tumor immune microenvironment, and ICIs treatment may be considered for those with some uncommon EGFR mutation subtypes.

Various Subtypes of EGFR Mutations in Patients With NSCLC Define Genetic, Immunologic Diversity and Possess Different Prognostic Biomarkers.

The prognosis of non-small cell lung cancer (NSCLC) patients has been comprehensively studied. However, the prognosis of resectable (stage I-IIIA) lung squamous cell carcinoma (LUSC) has not been thoroughly investigated at genomic and transcriptional levels.

Article	Year
Interleukin-1β-mediated suppression of microRNA-101 and upregulation of enhancer of zeste homolog 2 is involved in particle-induced lung cancer. Medical oncology (Northwood, London, England)\| PubMed ID: 25428391	2015
[Progress on the Study of Tumor Spread Through Air Spaces in the Clinicopathological Characteristics of Lung Adenocarcinoma and Its Influence on the Surgical Treatment and Prognosis of Lung ... Zhongguo fei ai za zhi = Chinese journal of lung cancer\| PubMed ID: 31196370	2019
Primary hepatoid adenocarcinoma of the lung in Yungui Plateau, China: A case report. World journal of clinical cases\| PubMed ID: 31367631	2019
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
Next-Generation Sequencing Reveals High Uncommon EGFR Mutations and Tumour Mutation Burden in a Subgroup of Lung Cancer Patients. Frontiers in oncology\| PubMed ID: 33889543	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
Various Subtypes of EGFR Mutations in Patients With NSCLC Define Genetic, Immunologic Diversity and Possess Different Prognostic Biomarkers. Frontiers in immunology\| PubMed ID: 35265073	2022
Mutational and Transcriptional Characterization Establishes Prognostic Models for Resectable Lung Squamous Cell Carcinoma. Cancer management and research\| PubMed ID: 36824152	2023
A rare case of pulmonary isolation combined with esophageal hiatal hernia. Asian journal of surgery\| PubMed ID: 37833229	2024
Migration of two clavicular Kirschner wires in different paths at different time: A case report. Asian journal of surgery\| PubMed ID: 38845315	2024

Yunfei Shi

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