Non-small Cell Lung Cancer Lung Research Articles

Relationship of intracellular proteolysis with CAP1 and cofilin1 in non-small-cell lung cancer

The main cause of death in non-small-cell lung cancer (NSCLC) is tumor progression, in which metastasis and invasion play an important role. The metastatic cascade is marked by a change in morphological, biological, biochemical and functional characteristics, including the acquisition of cellular mobility. The migration activity of tumor cells determines the work of actin-binding proteins that cause their functional partners CAP1 and cofilin. Of interest is the study of the regulation of working tandem CAP1/cofilin in NSCLC. The mechanism that regulates the level of proteins in cells is proteolysis, carried out by proteasomes and calpains. Therefore, the aim of this study was to estimate the expression of CAP1/CFL1 mRNA and their protein level in NSCLC tissues, and to analyze the possible mechanisms of their regulation by the proteasome and calpain systems. Samples of NSCLC and histological unchanged lung tissue were used (n = 42). The CAP1 and CFL1 mRNA expressions were determined by real-time PCR, the contents of proteins encoded by them were determined by Western blotting, and the activity of proteasomes and calpains by the fluorimetric method. There was an increase in the expression of mRNA and protein levels of CAP1 and cofilin in the tumor tissue compared with the unchanged lung tissue. The expression of mRNA and the level of CAP1 in tumor tissue increased during growth of the primary tumor. The cofilin level in the tumor tissue decreases against the background of increased expression of its mRNA. At the same time, during tumor growth, the activity of proteasomes and calpains increased. A negative regression relationships between the activity of proteasomes and the levels of CAP1 and cofilin, as well as the activity of calpains and the level of cofilin, were found. It can be assumed that proteasomes and calpains are involved in the degradation of CAP1 and cofilin. The data obtained suggest the importance of CAP1, cofilin and proteolytic systems in the tumor transformation and lymphogenous metastasis.

Machine learning based biomarkers to predict CD8 infiltration in non-small cell lung cancers using CT imaging.

e21145 Background: Immune-checkpoint inhibitors (ICIs), specifically monoclonal antibodies targeting the programmed cell death protein-1 and programmed death-ligand 1 (PD-1 and PD-L1) have shown promise in the treatment of non-small cell lung cancer (NSCLC). Unfortunately, patients response to ICI is difficult to predict, with cancer stage, treatment line and regimen all affecting response rates. Identification of patients who will be “responsive” to ICI is of great importance to increase treatment efficacy. Current techniques used to identify responsive patients rely on PD-L1/PD-1 expression, microsatellite instability, tumor mutagenic burden and less commonly CD8+ infiltration, all of which are invasive and costly procedures. In this study we aim to develop a machine learning derived CT imaging biomarker that predicts CD8 status of tumors, allowing for non-invasive determination of ICI treatment efficacy. Methods: To study CD8 infiltration we extracted patients that included CT scans and CD8 transcript data from publicly available cohorts (TCGA-LUSC, TCGA-LUAD, NSCLC-Radiogenomics) to produce the Lung3 cohort (104 patients). Using this cohort, we trained (80 patients) and tested (24 patients) an AI model to predict tumor CD8 infiltration using patient CT scans as the sole input. CD8 expression (high and low) was characterized using transcriptomic quantification and served as surrogate for CD8+ infiltration, following previously described methods. Supervised and unsupervised models previously trained to identify lung features were trained to identify CD8 status using the CD8 expression data provided in the Lung3 dataset. Algorithm performance was tested on a randomly chosen subset of the cohort (24 patients) and compared against transcriptomic confirmed CD8 expression. AUC were calculated for supervised and unsupervised models. Results: AUC for the supervised and unsupervised models generated using the Lung3 cohort are shown below. Our results suggest that the derived supervised and unsupervised models could identify the CD8 infiltration status using only patient CT scans in the test dataset. Conclusions: The machine learning based models described here show encouraging results suggesting that CT imaging of NSCLC lung cancers contain sufficient information to predict the CD8 infiltration status of tumors. Although these results are just a proof of concept, the promise of a CT based non-invasive marker for tumor immune status is encouraging to help advance treatment efficacy in the ever-growing field of ICI therapy.

Effects of histone deacetylase inhibitors Tricostatin A and Quisinostat on tight junction proteins of human lung adenocarcinoma A549 cells and normal lung epithelial cells.

Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for non-small cell lung cancer (NSCLC). However, more preclinical studies of HDAC inhibitors in NSCLC and normal lung epithelial cells are required to evaluate their antitumor activities and mechanisms. The bicellular tight junction molecule claudin-2 (CLDN-2) is highly expressed in lung adenocarcinoma tissues and increase the proliferation of adenocarcinoma cells. Downregulation of the tricellular tight junction molecule angulin-1/LSR induces malignancy via EGF-dependent CLDN-2 and TGF-β-dependent cellular metabolism in human lung adenocarcinoma cells. In the present study, to investigate the detailed mechanisms of the antitumor activities of HDAC inhibitors in lung adenocarcinoma, human lung adenocarcinoma A549 cells and normal lung epithelial cells were treated with the HDAC inibitors Trichostatin A (TSA) and Quisinostat (JNJ-2648158) with or without TGF-β. Both HDAC inhibitors increased anguin-1/LSR, decrease CLDN-2, promoted G1 arrest and prevented the migration of A549 cells. Furthermore, TSA but not Quisinostat with or without TGF-β induced cellular metabolism indicated as the mitochondrial respiration measured using the oxygen consumption rate. In normal human lung epithelial cells, treatment with TSA and Quisinostat increased expression of LSR and CLDN-2 and decreased that of CLDN-1 with or without TGF-β in 2D culture. Quisinostat but not TSA with TGF-β increased CLDN-7 expression in 2D culture. Both HDAC inhibitors prevented disruption of the epithelial barrier measured as the permeability of FD-4 induced by TGF-β in 2.5D culture. TSA and Quisinostat have potential for use in therapy for lung adenocarcinoma via changes in the expression of angulin-1/LSR and CLDN-2.

CD45RO⁺ Memory T Lymphocytes As A Candidate Marker for Non-small Cell Lung Cancer

背景与目的肺癌是世界范围内最常见的恶性肿瘤之一。肿瘤微环境中多种多样的免疫浸润细胞，是肿瘤免疫的重要组成，对患者预后具有临床意义。CD45RO+肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes, TILs），即记忆T细胞，其表达与多种肿瘤预后相关。本研究旨在探讨非小细胞肺癌（non-small cell lung cancer, NSCLC）中评估肿瘤和基质区CD45RO+ TILs密度与患者临床特征和预后的关系，及其联合程序性死亡受体配体1（programmed cell death-ligand 1, PD-L1）作为预后标志物的临床价值。方法对167例NSCLC患者的组织微阵列进行多重荧光免疫组织化学染色，标记CD45RO、细胞角蛋白（cytokeratin, CK）和PD-L1。利用人工智能图像识别技术和肿瘤细胞特异性CK染色，划分组织中的肿瘤区和基质区，评估肿瘤区和基质区CD45RO+ TILs的密度以及肿瘤细胞的PD-L1表达水平。采用非参检验分析CD45RO+ TILs与患者临床特征的关系，使用Kaplan-Meier方法和Cox风险比例模型分析CD45RO+ TILs独立或与PD-L1联合与肿瘤预后的关系。结果CD45RO+ TILs的密度与患者年龄、吸烟、肿瘤分期和病理类型显著相关。在NSCLC和肺腺癌（lung adenocarcinoma, LUAD）患者中，基质区高密度CD45RO+ TILs具有更长的总生存期（overall survival, OS）（NSCLC: P=0.007; LUAD: P < 0.001），并且是OS的独立预后因素（NSCLC: HR=0.559, 95%CI: 0.377-0.829, P=0.004; LUAD: HR=0.352, 95%CI: 0.193-0.641, P=0.001）。联合肿瘤细胞的PD-L1评分以及所有区域CD45RO+ TILs的浸润评分将患者分为四组：其中PD-L1+/CD45RO+患者无病生存期（disease-free survival, DFS）最长，PD-L1+/CD45RO-的患者DFS时间最短，并可作为DFS预后的独立因素（HR=2.221, 95%CI: 1.258-3.919, P=0.006）。结论肿瘤组织中CD45RO+ TILs密度以及CD45RO+ TILs联合肿瘤区PD-L1，与NSCLC的临床病理特征及预后显著相关，可作为新的生存预后标志物。

LncRNA LINC00473 promotes proliferation, migration, invasion and inhibition of apoptosis of non-small cell lung cancer cells by acting as a sponge of miR-497-5p.

Lung cancer is the leading cause of cancer-associated death worldwide and exhibits a poor prognosis. The present study aimed to determine the effect of long non-coding (lnc)RNA-LINC00473 on the development of non-small cell lung cancer (NSCLC) cells by regulating the expression of microRNA (miR)-497-5p. Reverse transcription-quantitative PCR was conducted to detect the level of LINC00473 and miR-497-5p. An MTT assay, flow cytometry and Transwell tests were performed to evaluate the proliferation, apoptosis, migration and invasion of NSCLC cells. Western blotting was performed to detect the expression of apoptosis- and migration-related proteins. RNA immunoprecipitation and a luciferase reporter assay were performed to verify the regulatory relationship between lncRNA-LINC00473 and miR-497-5p. LINC00473 expression was upregulated in lung cancer tissues and NSCLC cells (A549 and H1299) when compared with adjacent tissues or human bronchial epithelial cell lines and the 5-year survival rate was lower in patients with high LINC00473 expression compared with in patients with low LINC00473 expression. A negative correlation between LINC00473 and miR-497-5p was observed in lung cancer tissues. Proliferation, migration and invasion as well as the related protein levels were increased in A549 and H1299 transfected with pcDNA3.1-LINC00473, while the opposite results were obtained in A549 and H1299 transfected with small interfering (si)-LINC00473. Notably, it was demonstrated that LINC00473 could bind directly with miR-497-5p and inhibit its expression. miR-497-5p inhibitors reversed the effect of si-LINC00473. Furthermore, the present study demonstrated that LINC00473 promoted the malignant behaviour of NSCLC cells via regulating the ERK/p38 and MAPK signalling pathways and the expression of miR-497-5p.

Lung Cancer - Part I

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses both NSCLC and small cell lung cancer (SCLC), including lung cancer in those who have never smoked, prevention of lung cancer, with sections on diagnosis, biomarkers, treatment, and supportive care. This review contains 7 figures, 10 tables, and 81 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

Lung Cancer Part II

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses treatment of both NSCLC and small cell lung cancer (SCLC). This review contains 2 figures, 20 tables, and 95 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

Lung Cancer - Part I

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses both NSCLC and small cell lung cancer (SCLC), including lung cancer in those who have never smoked, prevention of lung cancer, with sections on diagnosis, biomarkers, treatment, and supportive care. This review contains 7 figures, 10 tables, and 81 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

48-Year-Old Woman With Dyspnea and Chest Pain

48-Year-Old Woman With Dyspnea and Chest Pain

AIMP3 inhibits cell growth and metastasis of lung adenocarcinoma through activating a miR-96-5p-AIMP3-p53 axis.

Aminoacyl‐tRNA synthetase‐interacting multifunctional protein‐3 (AIMP3) is a tumour suppressor, however, the roles of AIMP3 in non‐small cell lung cancer (NSCLC) are not explored yet. Here, we reported that AIMP3 significantly inhibited the cell growth and metastasis of NSCLC (lung adenocarcinoma) in vitro and in vivo. We have firstly identified that AIMP3 was down‐regulated in human NSCLC tissues compared with adjacent normal lung tissues using immunohistochemistry and western blot assays. Overexpression of AIMP3 markedly suppressed the proliferation and migration of cancer cells in a p53‐dependent manner. Furthermore, we observed that AIMP3 significantly suppressed tumour growth and metastasis of A549 cells in xenograft nude mice. Mechanically, we identified that AIMP3 was a direct target of miR‐96‐5p, and we also observed that there was a negative correlation between AIMP3 and miR‐96‐5p expression in paired NSCLC clinic samples. Ectopic miR‐96‐5p expression promoted the proliferation and migration of cancer cells in vitro and tumour growth and metastasis in vivo which partially depended on AIMP3. Taken together, our results demonstrated that the axis of miR‐96‐5p‐AIMP3‐p53 played an important role in lung adenocarcinoma, which may provide a new strategy for the diagnosis and treatment of NSCLC.

MiR-224-5p-enriched exosomes promote tumorigenesis by directly targeting androgen receptor in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC.

A single institutional experience with central lung stereotactic body radiation therapy demonstrating encouraging results with increased inter-fraction time.

BackgroundStereotactic body radiation therapy (SBRT) is an effective treatment modality for non-small cell lung cancer (NSCLC); however, there are concerns regarding potential toxicity for centrally located tumors.MethodsThis retrospective study considered patients with SBRT for central lung NSCLC (defined as a tumor within 2 cm of any mediastinal critical structure). The institutional protocol was that patients with central tumors received SBRT less frequently than daily—generally once or twice weekly.ResultsA total of 115 patients with 148 lesions were treated with SBRT to a median 45 [5–60] Gy in 4 [1–5] fractions over a median 5.3 [0–18] days. Many patients treated with this method presented with advanced disease: 58 treatments involved nodal targets, and 42 had stage 3 disease. 52% of patients had chronic obstructive pulmonary disease (COPD), and only 49% had a biopsy, often due to concerns regarding other medical comorbidities. Rates of prior chemotherapy, thoracic surgery, and thoracic radiotherapy were 32%, 21%, and 49%, respectively. Via the Kaplan-Meier method, 2-year overall survival was 65%, and 2-year local control was 77%. Two-year local-progression free survival was 53%, and 2-year progression-survival was 48%. Treatments for stage 3 disease had an impressive 82% 2-year local control that was comparable to early stage treatments. Patients with stage 3 disease had a 2-year overall survival of 59%, which trended towards decreased overall survival compared to early stage patients. There were 13 grade 1 (9%) and 14 grade 2 (9%) toxicities. There were no reported grade ≥3 acute or late toxicities and only 3 cases of pneumonitis.ConclusionsOur series demonstrates encouraging local control with low rates of toxicity for central lung SBRT, including many stage 3 patients. This may be the result of the relatively large inter-fraction interval. This interval may allow for greater tumor effects (such as reoxygenation) and improved tolerance from normal tissues.

Discovery of Small Molecule Bak Activator for Lung Cancer Therapy.

Rationale: Bak is a major proapoptotic Bcl2 family member and a required molecule for apoptotic cell death. High levels of endogenous Bak were observed in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines. Increased Bak expression was correlated with poor prognosis of NSCLC patients, suggesting that Bak protein is an attractive target for lung cancer therapy. The BH3 domain functions as death domain and is required for Bak to initiate apoptotic cell death. Thus, the BH3 domain is attractive target for discovery of Bak agonist.Methods: The BH3 death domain binding pocket (aa75-88) of Bak was chosen as a docking site for screening of small molecule Bak activators using the UCSF DOCK 6.1 program suite and the NCI chemical library (300,000 small molecules) database. The top 500 compounds determined to have the highest affinity for the BH3 domain were obtained from the NCI and tested for cytotoxicity for further screening. We identified a small molecule Bak activator BKA-073 as the lead compound. The binding affinity of BKA-073 with Bak protein was analyzed by isothermal titration calorimetry (ITC) assay. BKA-073-mediated Bak activation via oligomerization was analyzed by a cross-linking with Bis (maleimido) hexane (BMH). Sensitivity of BKA-073 to lung cancer cells in vitro was evaluated by dynamic BH3 profiling (DBP) and apoptotic cell death assay. The potency of BKA-073 alone or in combination with radiotherapy or Bcl2 inhibitor was evaluated in animal models.Results: We found that BKA-073 binds Bak at BH3 domain with high affinity and selectivity. BKA-073/Bak binding promotes Bak oligomerization and mitochondrial priming that activates its proapoptotic function. BKA-073 potently suppresses tumor growth without significant normal tissue toxicity in small cell lung cancer (SCLC) and NSCLC xenografts, patient-derived xenografts, and genetically engineered mouse models of mutant KRAS-driven cancer. Bak accumulates in radioresistant lung cancer cells and BKA-073 reverses radioresistance. Combination of BKA-073 with Bcl-2 inhibitor venetoclax exhibits strong synergy against lung cancer in vivo.Conclusions: Development of small molecule Bak activator may provide a new class of anticancer agents to treat lung cancer.

Immune Escape Mechanisms in Non Small Cell Lung Cancer.

Simple SummaryImmune escape mechanisms have been identified in every step of lung tumorigenesis. A heterogeneous ensemble of immune evasion processes shapes the evolution of precursor lesions towards the invasive phase, contributes to fostering progression from early stage to metastatic disease and defines the main immunological features of specific lung cancer molecular subsets. By disabling distinct phases of the cancer immunity cycle, from antigen presentation to activation of T cell-mediated immunity, and from antigen-specific T cell recruitment to tumor recognition, immune escape in non small cell lung cancer (NSCLC) represents one of the major hurdles to be overcome to improve clinical outcome in patients treated with immunotherapy targeting immune checkpoints.Development of strong immune evasion has been traditionally associated with the late stages of solid tumor progression, since advanced cancers are more likely to have reached the third phase of the immunoediting process. However, by integrating a variety of approaches, evidence for active immune escape mechanisms has been found even in the pre-invasive lesions that later progress to the main NSCLC histotypes. Pre-invasive lesions of adenocarcinoma (LUAD) and of squamous cell carcinoma (LUSC) can show impaired antigen presentation, loss of heterozygosity at the Human Leukocyte Antigen (HLA) region, neoantigen silencing, activation of immune checkpoints, altered TH1/TH2 cytokine ratios, and immune contexture evolution. Analysis of large panels of LUAD vs. LUSC, of early stage NSCLC vs. normal lung tissue, of specific molecular subsets of NSCLC, and of distinct regions within the same tumor, indicates that all these processes of immune escape continue to evolve in the invasive stage of NSCLC, are associated with inter- and intra-tumor heterogeneity, and contribute to resistance to therapy by immune checkpoint blockade (ICB). In this review, we will discuss the most recent evidence on immune escape mechanisms developing from the precursor to invasive stage in NSCLC, and the contribution of immune evasion to resistance to ICB in lung cancer.

How selecting best upfront therapy for metastatic disease?-Focus on ROS1-rearranged disease.

ROS proto-oncogene 1 (ROS1) rearrangements defines a distinct group of non-small cell lung cancer (NSCLC), mainly represented by younger subjects, never smokers and with adenocarcinoma histology. Fusions involving ROS1 gene are present in 1-2% of lung adenocarcinomas and other solid tumors. Identification of patients harboring ROS1 rearrangements is a critical issue and current guidelines recommend screening of all advanced non-squamous NSCLC and certain squamous lung cancer patients. A number of trials have supported crizotinib as the best option for NSCLC patients with ROS1 translocations, irrespective of line of therapy. Unfortunately, the majority of patients become insensitive to crizotinib, due to the occurrence of secondary ROS1 mutations or failure within the central nervous system (CNS). Several highly potent and CNS penetrant ROS1 inhibitors have been developed and recent data highlight their potential role in the front-line treatment of this disease. Among them entrectinib, also known as RXDX-101, is a potent second-generation, multitarget oral inhibitor against the neurotrophin receptors TRKA, TRKB, TRKC ALK, and ROS1 with the ability to cross the blood-brain barrier. In the next few years, results of ongoing trials with novel ROS1 inhibitors and dedicated translational research studies might help to define the optimal sequence of treatment for ROS1-positive NSCLC patients.

MicroRNA-877 contributes to decreased non-small cell lung cancer cell growth via the PI3K/AKT pathway by targeting tartrate resistant acid phosphatase 5 activity

ABSTRACT Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in both men and women. microRNAs (miRs) can exert important functions in cancer development. However, the role of miR-877 in NSCLC as it relates to tartrate resistant acid phosphatase 5 (ACP5) is unknown. For this study, the gain-and-loss-of-function experiments were performed to explore the effects of miR-877 and ACP5 on NSCLC. miR-877 expression in LC and paracancerous tissues, lung epithelial cell line and NSCLC cell lines was detected, and the association between miR-877 expression and clinical features of LC patients was analyzed. The levels of ACP5, epithelial-mesenchymal transition (EMT) markers and apoptosis-related proteins were measured. In vivo experiments were conducted for further validation. Consequently, we found that miR-877 expression was lowered in LC tissues and cell lines, and correlated with clinical stage, differentiation, lymph node metastasis and prognosis of NSCLC patients. Additionally, miR-877 was determined to inhibit ACP5 activity, and miR-877 downregulated the PI3K/AKT pathway by silencing ACP5. Furthermore, overexpression of miR-877 inhibited the viability, migration, invasion and EMT of NSCLC cells, but promoted cell apoptosis. In conclusion, miR-877 overexpression inhibited malignant biological behaviors of NSCLC cells by downregulating ACP5 and inactivating the PI3K/AKT pathway.

SNHG3 Knockdown Suppresses Proliferation, Migration and Invasion, and Promotes Apoptosis in Non-Small Cell Lung Cancer Through Regulating miR-216a/ZEB1 Axis.

BackgroundTumour growth and development are dependent on many factors including long noncoding RNAs (lncRNAs). However, limited information is available on the involvement of lncRNAs in non-small cell lung cancer (NSCLC) and the molecular mechanisms have not been defined. Here, we examined the expression of small nucleolar RNA host gene 3 (SNHG3) and its contribution to the development of NSCLC.MethodsWe detected SNHG3, miR-216a, and ZEB1 expression in tissues from NSCLC patients and lung adenocarcinoma cell lines using quantitative real-time polymerase chain reaction. Proliferation, migrations, invasion, and apoptosis of tumour cells were assessed using cell counting kit-8, transwell experiments, and flow cytometry after SNHG3 knockdown by small interfering RNAs. Bioinformatics and luciferase reporter assays were employed for analysing the interactions between SNHG3, miR-216a, and ZEB1.ResultsWe found highly upregulated SNHG3 in tissues and cells from NSCLC patients, which was linked to poor prognosis. SNHG3 silencing diminished the ability of NSCLC cells to proliferate, migrate, and invade and promoted apoptosis. Furthermore, SNHG3 competed with endogenous RNA and enhanced the expression of ZEB1 by interfering with miR-216a. ZEB1 overexpression or miR-216a blockade reversed SNHG3-induced tumour inhibition. Similar effects were observed in vivo where SNHG3 knockdown inhibited NSCLC tumour growth by reducing expression of miR-216a while increasing that of ZEB1.ConclusionKnockdown of SNHG3 inhibits NSCLC tumour development and progression by upregulation of ZEB1 and interference with miR-216a, revealing an attractive alternative target for patients with NSCLC.

Elevated pretreatment plasma fibrinogen level is associated with metastasis of non-small cell lung cancer (NSCLC)

Abstract Objective The aim of this study was to investigate the correlation between pretreatment fibrinogen levels and metastasis in non-small cell lung cancer (NSCLC). Methods The study included 503 NSCLC patients with a clear pathological diagnosis and 168 patients diagnosed with benign lung diseases by histological examination. Pretreatment plasma fibrinogen values were quantified, and the relationship between plasma fibrinogen level and clinical variables comprising tumor size, metastasis, and clinical stage was examined using Kruskal-Wallis test, Wilcoxon rank sum test, and Chi-square test. Results The median plasma fibrinogen values were statistically higher in NSCLC patients with metastasis than patients with benign lung diseases and NSCLC patients without metastasis (Kruskal-Wallis test; P &lt; 0.001). Plasma fibrinogen values were also significantly higher in advanced clinical stages (Wilcoxon rank sum test; P &lt; 0.001). A significant relationship was observed between elevated fibrinogen (&gt; 2.974 g/L) and metastasis, clinical stage, and tumor size (Chi-square test; P &lt; 0.001). Conclusion This correlation suggests that elevated pretreatment plasma fibrinogen levels can predict metastasis and advanced tumor stage in NSCLC patients.

Traitements locaux : indication et résultats dans les stades précoces: Local treatments: Indication and results in early stages

AbstractLobectomy with radical lymph node dissection remains the gold standard treatment for stage I primary non-small cell lung cancer (NSCLC). The spontaneous evolution of NSCLC lung tumors is very negative; the use of local non-surgical treatments is an major option for the care of these fragile patients who are not eligible for surgery. In recent years, stereotaxic radiotherapy (SBRT) and percutaneous ablation techniques (or percutaneous tumor destruction) have gradually taken their place in this indication.The choice of doses and fractionation and the stereotactic radiotherapy technique should be considered taking into account the patient’s clinical situation, previous treatments and the tumour to be treated (size and topography). Iterative treatments, catch-up treatments in case of failure of one of the type of treatments and reirradiations offer new perspectives for patients, replacing or delaying the use of systemic treatment. Finally, improved knowledge of response patterns on scan and metabolic imaging has helped to ensure safe and reliable patient follow-up.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.