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Background: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC., Methods: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway., Results: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007)., Conclusions: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer., (© 2022. The Author(s).)

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Increasing evidence has shown that microRNAs (miRNAs) play a significant functional role by directly regulating respective targets in cancer stem cell (CSC)-induced non-small cell lung cancer (NSCLC) progression and resistance to therapy. In this study, we found that hsa-miR-124a was downregulated during spheroid formation of the NSCLC cell lines SPC-A1 and NCI-H1650 and NSCLC tissues compared with normal lung cells and tissues. Patients with lower hsa-miR-124a expression had shorter overall survival (OS) and progression free survival (PFS). Moreover, ubiquitin-specific protease 14 (USP14) was confirmed to be a direct target of hsa-miR-124a. Furthermore, concomitant low hsa-miR-124a expression and high USP14 expression were correlated with a shorter median OS and PFS in NSCLC patients. Cellular functional analysis verified that the tumor suppressor hsa-miR-124a negatively regulated cell growth and self-renewal, and promoted apoptosis and gefitinib sensitivity of lung cancer stem cells by suppressing its target gene USP14. Our results provide the first evidence that USP14 is a direct target of hsa-miR-124a, and that hsa-miR-124a inhibits stemness and enhances the gefitinib sensitivity of NSCLC cells by targeting USP14. Thus, hsa-miR-124a and USP14 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for clinical diagnosis of mediastinal lymphadenectasis. This study aimed to evaluate the diagnostic significance of EBUS-TBNA for mediastinal lymphadenectasis in a large single center., Methods: A total of 846 patients who were not definitively diagnosed with mediastinal lymphadenectasis underwent EBUS-TBNA were retrospectively analyzed in this study., Results: In total, 842 patients underwent EBUS-TBNA successfully. There were 589 patients with malignancy, including squamous carcinoma (118 cases; 20.6%), adenocarcinoma (187 cases; 32.7%) and small cell carcinoma (88 cases; 15.4%). A total of 253 patients were diagnosed with benign disease, including tuberculosis (111 cases; 43.9%) and sarcoidosis (93 cases; 36.7%). The diagnostic sensitivity of lung cancer, tuberculosis and sarcoidosis were 94.4%, 81.1% and 51.6%, respectively. The overall sensitivity of EBUS-TBNA was 92.0%. N2 stage in lung cancer patients who were diagnosed by EBUS-TBNA was significantly higher than other stages. The positive rate of targeted puncture is high for the lymph nodes whose short-axis diameters were larger than 1 cm., Conclusion: The operation risk of EBUS-TBNA is relatively small. In diseases complicated by mediastinal lymphadenectasis, malignant diseases are most, and benign diseases mainly are granulomatous. EBUS-TBNA is a valuable diagnostic technique in patients with mediastinal lymphadenectasis whose diagnosis have not been determined., (© 2015 John Wiley & Sons Ltd.)

Objective: This study aims to explore the expression pattern and prognostic significance of miR-33a in non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy., Methods: MiR-33aexpression in NSCLC was analyzed in silico using the GEO database and was subsequently confirmed by quantitative RT-PCR in 147 NSCLC biopsies. Among these, 32 of these biopsies were paired with adjacent non-neoplastic tissues. The survival analysis of NSCLC by Kaplan-Meier estimates was stratified based on miR-33a expression. In addition, multivariate survival analysis in corresponding groups of NSCLC patients was conducted by Cox proportional hazards regression model., Results: The in silico analysis of miR-33a expression in NSCLC resulted to its down-regulation in different tumor types. The expression level of miR-33a was lower in each grade of NSCLC tumor biopsies than in normal lung tissues. Univariate and multivariate survival analysis further established that low miR-33a expression was an important risk factor for overall survival and disease free survival in NSCLC patients., Conclusion: Our study implied that miR-33a expression levels may have an essential role in NSCLC progression, and could act as a specific and sensitive biomarker for NSCLC patients who have undergone adjuvant chemotherapy., Competing Interests: The authors have declared that no competing interests exist.

Background: Activating mutations of epidermal growth factor receptor (EGFR) could predict response to tyrosine kinase inhibitor (TKI) treatment in patients with non-small cell lung cancer (NSCLC). However, the detection of EGFR mutation is frequently challenging in clinical practice for the lack of tumor tissue. The aim of this study was to investigate the feasibility of performing EGFR mutation testing on various types of liquid-based cytology (LBC) samples., Materials and Methods: A total of 434 liquid-based cytology samples were collected from March 2010 and November 2013. Among them, 101 with diagnosis of lung adenocarcinoma had paired surgically resected specimens. The ADx Amplification Refractory Mutation System (ADx-ARMS) was used to determine EGFR mutation status both in LBC and resected samples., Results: All liquid-based cytology samples were adequate for EGFR mutation analysis. The mutation rate was 50.5% in the 434 NSCLC patients with LBC samples and the incidence rates of EGFR mutation were consistent among different specimens. We also detected EGFR positives in 52.5% (53/101) patients with paired histologic specimens. The concordance rate of EGFR mutation between LBC samples and paired histologic specimens was 92.1%., Conclusions: Our results suggest that liquid-based cytology samples are highly reliable for EGFR mutation testing in patients with NSCLC.

Objective: To study the clinical manifestations and radiological characteristics, diagnostic methods and outcomes of pulmonary mucosa-associated lymphoid tissue-derived(MALT) lymphoma., Methods: A retrospective review of clinical, radiological and follow-up data of 29 pulmonary MALT lymphoma cases at Shanghai Pulmonary Hospital affiliated to Tong Ji University from January 2002 to June 2010 was performed., Results: Among these patients, there were 19(65.5%) males and 10 (34.5%) females aged from 27 to 73 (median 53) years old. Common clinical manifestations were cough (51.7%), fever (20.7%), apnea (17.2%), chest pain (17.2%), fatigue (13.8%) and weight loss (13.8%), while 9(31.0%) cases had no symptoms at diagnosis. The characteristics of the chest CT showed that 22 (75.9%) of the cases had patch infiltration or consolidation of the lung, 7(24.1%) of the cases had mass, and 15 (51.7%) unilateral and 14(48.3%) bilateral lesions. Their diagnosis duration varied between 0.5 and 96 months. 18(62.1%) cases were confirmed by surgery (15 open lung and 7 video-assisted thoracic surgery, VAST), 4 (13.8%) by percutaneous lung biopsy, 5 (17.2%) by bronchoscopic biopsy, and 2 (6.9%) by peripheral lymph node biopsy. The treatment methods included surgery, combined chemotherapy, radiotherapy and Chinese herbal medicine. The 1- and 3-year-survival rates were 92.3% and 87.4%, respectively., Conclusions: Pulmonary MALT lymphoma is atypical in clinical manifestations and radiological characteristics, and easy to be misdiagnosed. Local diseases are mainly treated by operation while extensive diseases receive combined chemotherapy. A proper diagnosis is mainly based on pathological biopsy. Patients with MALT lymphoma have a favorable outcome. Poor prognosis may be connected with poor performance status and long diagnosis duration.