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.

Recent evidence indicated that neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L) has a critical role in the regulation of cellular processes such as apoptosis, transport and metastasis, and is downregulated in several types of cancers. However, the role of NEDD4L in non-small cell lung cancer (NSCLC) has not been fully elucidated. In this study, we demonstrated that NEDD4L was downregulated in NSCLCs. This downregulation correlated with lymph node invasion, advanced stage and poor survival. In vitro experiments revealed that NEDD4L significantly suppressed cell proliferation, migration and invasion abilities. Further in vivo assay demonstrated that knocking down of NEDD4L enhanced the tumor metastasis of NSCLC cells. Moreover, we found that Polycomb group protein enhancer of zeste homologue 2 (EZH2) mediated H3K27 methylation was involved in the downregulation of NEDD4L. Knocking down of EZH2 restored the expression of NEDD4L. Further examined by luciferase reporter assay indicated the EZH2 regulated the transcription activity of NEDD4L. In clinical samples, EZH2 was inversely correlated with NEDD4L expression. In summary, NEDD4L acted as a tumor suppressor gene in NSCLC and targeting EZH2 could upregulate NEDD4L expression, which might serve as a novel approach for NSCLC.

Decreased expression of NEDD4L contributes to NSCLC progression and metastasis.

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.

Based on a thorough analysis of monotherapy (pembrolizumab) and chemoimmunotherapy, the immunomodulatory effects of chemotherapy agents are emphasized.

The prospect of immunotherapy combined with chemotherapy in patients with advanced non-small cell lung cancer: a narrative review.

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.

To comprehensively analyze the stemness characteristics related to prognosis and the immune microenvironment in lung adenocarcinoma (LUAD).

Integrative stemness characteristics associated with prognosis and the immune microenvironment in lung adenocarcinoma.

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
Decreased expression of NEDD4L contributes to NSCLC progression and metastasis. Biochemical and biophysical research communications\| PubMed ID: 30967264	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
The prospect of immunotherapy combined with chemotherapy in patients with advanced non-small cell lung cancer: a narrative review. Annals of translational medicine\| PubMed ID: 34988212	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
Integrative stemness characteristics associated with prognosis and the immune microenvironment in lung adenocarcinoma. BMC pulmonary medicine\| PubMed ID: 36471379	2022
Mutational and Transcriptional Characterization Establishes Prognostic Models for Resectable Lung Squamous Cell Carcinoma. Cancer management and research\| PubMed ID: 36824152	2023

Jin Duan

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