scholarly journals LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Longzhen Piao ◽  
Zhaoting Yang ◽  
Ying Feng ◽  
Chengye Zhang ◽  
Chunai Cui ◽  
...  
Keyword(s):  
Cox Regression ◽  
Transmembrane Protein ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Small Cell ◽  
Cancer Prognosis ◽  
Normal Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Abstract Background Although the leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is one of the mitochondrial inner membrane proteins that is involved in cancer prognosis in various tumors, LETM1 as a biomarker for prognostic evaluation of non-small cell lung carcinoma (NSCLC) has not been well studied. Methods To address this issue, we used 75 cases NSCLC, 20 cases adjacent normal lung tissues and NSCLC cell lines. We performed immunohistochemistry staining and western blot analysis as well as immunofluorescence imaging. Results Our studies show that expression of LETM1 is significantly correlated with the lymph node metastasis (p = 0.003) and the clinical stage (p = 0.005) of NSCLC. The Kaplan-Meier survival analysis revealed that NSCLC patients with positive expression of LETM1 exhibits a shorter overall survival (OS) rate (p = 0.005). The univariate and multivariate Cox regression analysis indicated that LETM1 is a independent poor prognostic marker of NSCLC. In addition, the LETM1 expression is correlated with cancer stemness-related gene LGR5 (p < 0.001) and HIF1α expression (p < 0.001), but not with others. Moreover, LETM1 expression was associated with the expression of cyclin D1 (p = 0.003), p27 (p = 0.001), pPI3K(p85) (p = 0.025), and pAkt-Thr308 (p = 0.004). Further, our studies show in LETM1-positive NSCLC tissues the microvessel density was significantly higher than in the negative ones (p = 0.024). Conclusion These results indicate that LETM1 is a potential prognostic biomarker of NSCLC.

scholarly journals In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Lygia Bertalha Yaegashi ◽  
Camila Machado Baldavira ◽  
Tabatha Gutierrez Prieto ◽  
Juliana Machado-Rugolo ◽  
Ana Paula Pereira Velosa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cox Regression ◽  
Cytotoxic T Cells ◽  
Small Cell ◽  
Malignant Cells ◽  
Pathological Stage ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors’ immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8+, Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers—the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III &gt; 24.89 fibers/mm². Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression &gt; 52.86 cells/mm² and CD3+ ≤ 278.5 cells/mm². We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.

scholarly journals Small-Cell Carcinoma Transformation of Pulmonary Adenocarcinoma after Osimertinib Treatment: A Case Report

2018 ◽  
Vol 11 (2) ◽  
pp. 323-329 ◽  
Author(s):  
Yuri Taniguchi ◽  
Hajime Horiuchi ◽  
Teppei Morikawa ◽  
Kazuhiro Usui
Keyword(s):  
Kinase Inhibitors ◽  
Lung Tumor ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Acquired Resistance ◽  
Small Cell ◽  
Pulmonary Adenocarcinoma ◽  
Metastatic Lung Tumor ◽  
T790m Mutation ◽  
Cell Lung Carcinoma

There are various mechanisms underlying the resistance of EGFR-mutant lung adenocarcinoma to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We herein report a case of pulmonary adenocarcinoma with EGFR mutation (exon 19 deletion and T790M) that acquired resistance to osimertinib treatment because of transformation into small-cell lung carcinoma (SCLC). A 67-year-old ex-smoking woman was diagnosed with left upper lobe adenocarcinoma of clinical stage IIIA (cT2bN2M0). She was treated with chemoradiotherapy (cisplatin and vinorelbine plus radiation), gefitinib, cisplatin, and pemetrexed followed by pemetrexed maintenance therapy and erlotinib. Since a sample extracted from the metastatic lung tumor taken obtained via a transbronchial lung biopsy was found to be positive for the T790M mutation at the time of disease progression during erlotinib treatment, she received osimertinib treatment for 15 months until progressive disease. She developed resistance to osimertinib due to the histologic transformation to SCLC. Although the standard chemotherapy of carboplatin and etoposide for SCLC was administered, she died due to metastatic liver failure.

Radiotherapy for Medically Inoperable Non-Small Cell Lung Cancer at Clinical Stage I and II

2003 ◽  
Vol 89 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Kazunari Yamada ◽  
Toshinori Soejima ◽  
Yosuke Ota ◽  
Ryohei Sasaki ◽  
Eisaku Yoden ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Local Control ◽  
Significant Influence ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Survival Rates ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cause Specific Survival

We reviewed the records of 36 patients with medically inoperable stage l-ll non-small cell lung carcinoma who were treated with radiotherapy. The median dose to the target was 60 Gy with conventional fractionation. Fifteen patients were treated without elective irradiation fields, while the remaining 21 were treated with extended fields including elective mediastinal regional lymph nodes. The overall survival rates at three and five years were 32.3% and 18.8%, the cause-specific survival rates were 40.9% and 27.3%, and the local control rates were 31.7% and 23.8%, respectively. In multivariate analysis the radiation dose had a marginally significant influence on the cause-specific survival, while tumor size had a significant influence on the local control rate. Only one patient had relapse in the regional mediastinal lymph nodes as the only site of metastasis. We conclude that the dose used in the present study is inadequate and recommend that further efforts be made to improve local control by dose escalation within a small target volume.

scholarly journals miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

2019 ◽  
Vol 27 (1) ◽  
pp. 15-24
Author(s):  
Li-Wei Gao ◽  
Guo-Liang Wang
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Normal Lung ◽  
Ppi Network ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Network Modules ◽  
Tcga Dataset

Abstract Lung cancer (LC), which includes small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), is common and has a high fatality rate. This study aimed to reveal the prognostic mechanisms of LC. GSE30219 was extracted from the Gene Expression Omnibus (GEO) database, and included 293 LC samples and 14 normal lung samples. Differentially expressed genes (DEGs) were identified using the Limma package, and subjected to pathway enrichment analysis using DAVID. MicroRNAs (miRNAs) targeting the DEGs were predicted using Webgestalt. Cytoscape software was used to build a protein-protein interaction (PPI) network and to identify significant network modules. Survival analysis was conducted using Survminer and Survival packages, and validation was performed using The Cancer Genome Atlas (TCGA) dataset. The good and poor prognosis groups contained 518 DEGs. miR-190, miR-493, and miR-218 for the upregulated genes and miR-302, miR-200, and miR-26 for the downregulated genes were predicted. Three network modules (module 1, 2, and 3) were identified from the PPI network. CDK1, MCM10, and NDC80 were the core nodes of module 1, 2, and 3, respectively. In module 1, CDK1 interacted with both CCNB1 and CCNB2. Additionally, CDK1, CCNB1, CCNB2, MCM10, and NDC80 expression levels correlated with clinical survival and were identified as DEGs in both GSE30219 and the TCGA dataset. miR-190, miR-493, miR-218, miR-200, and miR-302 might act in LC by targeting the DEGs. CDK1, CCNB1, CCNB2, MCM10, and NDC80 might also influence the prognosis of LC.

scholarly journals P14.40 Incidence and risk factors identification for lung cancer brain metastasis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii76-iii76
Author(s):  
H Fariña ◽  
M Rodríguez-Salazar ◽  
M Rodríguez-Yanes ◽  
J Plata-Bello
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Cox Regression ◽  
Small Cell Lung Carcinoma ◽  
Malignant Neoplasm ◽  
Small Cell ◽  
Rank Test ◽  
Cell Lung Carcinoma ◽  
New Diagnosis

Abstract BACKGROUND Lung Cancer (LC) is the most frequent malignant neoplasm around the world and it is one of the most frequent brain metastasis origins. The aim of the present work is to measure the incidence of brain metastasis in new-diagnosed LC patients and to identify the risk factors associated with its development. MATERIAL AND METHODS A retrospective observational study has been performed. Patients with new diagnosis of LC between January 2015 and December 2016 in our Center were included. Demographic, clinical and molecular variables were studied. Statistical analysis included a uni- and multivariate COX regression, survival analysis (log-rank test) and non-parametric two-independent sample tests. RESULTS Three-hundred and thirty-nine patients were diagnosed with LC in our Center between 2015 and 2016 (99 female; mean age: 66.1 years, SD=10.89). The incidence of brain metastasis was 16.25 cases each year since the initial diagnosis (19.2% of all patients). The risk of brain metastasis was increased in the first year after the diagnosis of LC (83.07% of cases). Patients with metastasis were younger than non-metastatic patients (64.0 vs. 66.6 years of age; p=.041). Small-cell lung carcinoma was the most frequent histological subtype associated with the development of metastasis (HR=2.267; p=.011), followed by the adenocarcinoma (HR=1.131; p=.624) and epidermoid (HR=.546; p=.067). No molecular factor (EGFR, ALK or p63 expression) was identified as risk factor. The overall survival of brain-metastatic patients was significantly lower than non-metastatic patients (167.0 vs. 273.0 days; p=.0002). CONCLUSION Brain metastasis are diagnosed in almost 20% of LC patients with, at least, three-years follow-up. Small-cell carcinoma subtype and younger patients were associated with a higher risk of brain metastasis, which is associated with a bad prognosis.

Results of stereotactic body radiation therapy (SBRT) for T2 lung cancer: Outcomes of longer term follow-up.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8542-8542 ◽  
Author(s):  
Stephen Shamp ◽  
Tangel C. Chang ◽  
Tithi Biswas ◽  
Philip Aaron Linden ◽  
Yaron Perry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Small Cell Lung Carcinoma ◽  
Combined Modality Therapy ◽  
High Rate ◽  
Tumor Diameter ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

8542 Background: SBRT is a well-established, highly efficacious treatment for T1N0 non-small cell lung carcinoma (NSCLC). Its efficacy in T2N0 cancers is less clear. This is a review of our institutional experience with long-term follow-up. Methods: 45 patients with medically inoperable T2 N0/Nx M0 NSCLC who were treated with definitive SBRT between 2009 and 2013 were analyzed retrospectively. All patients underwent PET/CT staging and fiducial marker placement for image guided therapy with the Cyberknife platform. Radiation dose was 50 Gray in 5 fractions (N = 24), 50 Gray in 4 fractions (N = 11) or 54-60 Gray in 3 fractions (N = 10) delivered over 7 to 14 days. We analyzed overall survival from the date of start of SBRT, and we performed analyses actuarially using Cox regression analysis and Kaplan-Meier survival analysis for comparisons of hazard ratio (HR) among subgroups. Results: 45 patients were studied (median age 74). The 5-year actuarial overall survival was 18.7% (39.3% at 2 years), with most patients dying from lung cancer recurrence/progression outside of the treatment field. Subgroup analyses showed no statistically significant differences with respect to age, gender, histology, nominal radiation prescription dose, tumor diameter or PTV target volume (median PTV 87cc). There was statistically significantly better survival associated with increased maximum biologically effective dose (BED10) of radiation at the center of the tumor (p = 0.03). Conclusions: Unlike the outcomes for T1 NSCLC, our results in T2 NSCLC were disappointing, with a high rate of out-of-field failure and death from lung cancer. We stress the importance of diagnosis and treatment of NSCLC at the T1N0 stage. We suggest that patients with T2N0/Nx NSCLC be considered for SBRT dose intensification and/or combined modality therapy protocols.

scholarly journals Transcription Factor KLF4: A Potential Biomarker of Non-small Cell Lung Cancertranscription Factor KLF4: A Potential Biomarker of Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Jixin Zhang ◽  
Yanping Wu ◽  
Lianjun Lin ◽  
Xinmin Liu
Keyword(s):  
Lung Cancer ◽  
Cell Carcinoma ◽  
Clinical Stage ◽  
Small Cell ◽  
Clinicopathological Features ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Klf4 Expression ◽  
Potential Biomarker ◽  
Significant Difference

Abstract Background Krüppel-like factor 4 (KLF4) is a member of the zinc finger transcription factor family and plays an important role in cell proliferation, differentiation, apoptosis, embryonic development, organ formation, and tumor invasion. There is little research on the clinicopathological characteristics and KLF4 expression in non-small cell lung cancer (NSCLC). Methods We conducted a retrospective study to further explore the correlation between KLF4 expression and clinicopathological features of NSCLC by immunohistochemical staining. Results This study included 81 males (52.3%), 74 females (47.7%), and 101 (65.2%) ages <65, 54 (34.8%) ages ≥65 years. A total number of 127 cases (81.9%) were adenocarcinoma, 26 cases (16.8%) were squamous cell carcinoma, and 2 cases (1.3%) were large cell carcinoma. There were 140 patients (89.7%) in T1-T2 phase and 15 patients in T3-T4 phase; 130 patients (83.9%) in N0 phase and 25 patients (16.1%) in N1-N3 phase. There were no distant metastases in 154 patients (99.4%), and only 1 patient (0.6%) was in M1 phase. In terms of clinical stage, 142 patients (91.6%) in stage I-II and 13 patients (8.4%) in stage III-IV. The number of patients with smoking history was 40 (25.8%). KLF4 expression in NSCLC tissues was significantly decreased compared with normal lung tissues (P<0.001); KLF4 expression in adenocarcinoma was lower than that in normal lung tissues (P<0.001), while there was no significant difference in quamous cell carcinoma (P=0.314). Higher KLF4 expression was significantly associated with clinicopathological features of NSCLC such as squamous cell carcinoma (P<0.001), later T stage (T3-T4 stage) (P=0.013), lymph node metastasis (P=0.011), later clinical stage (III-IV stage) (P=0.001). KLF4 expression was not associated with age (P=0.082); there was no significant difference in KLF4 expression between male and female patients with adenocarcinoma (P=0.709). It was also found that KLF4 was positively correlated with Ki-67 expression in patients with adenocarcinoma (r=0.272, P=0.002). Conclusions Aboval all, the tumor suppressor gene KLF4 might become a potential biomarker and a new therapeutic target for lung cancer patients.

Prognostic value of microRNAs (miRs) expression in stage I-IIIA lung adenocarcinoma (AC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11069-11069
Author(s):  
Marcin Tomasz Skrzypski ◽  
Krzysztof Goryca ◽  
Piotr Czapiewski ◽  
Ewa Jassem ◽  
Wojciech Biernat ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Pulmonary Resection ◽  
Cox Regression ◽  
Geometric Mean ◽  
Clinical Stage ◽  
Distant Metastases ◽  
Disease Recurrence ◽  
Stage I ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

11069 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select high-risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value of 22 miRs in frozen samples of early squamous cell lung carcinoma, and the feasibility of their assessment in formalin fixed paraffin embedded (FFPE) samples (Skrzypski et. al. J Clin Oncol 2010;28;15s). In this study, we investigated the expression of 350 microRNAs in operable AC pts. Methods: FFPE tumor samples were obtained from 80 stage I-IIIA pts who underwent curative pulmonary resection, 48% of whom subsequently developed distant metastases. Median follow-up of pts who were disease recurrence-free was 5.8 years (range, 4.0-9.1 years). RNA was isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 350 miRs was analyzed by qRT-PCR (Appliedbiosystems). Raw data were normalized vs. the geometric mean of U6, RNU48 and RNU44 expression. Relative miRs expression was correlated with distant metastases-free survival (MFS) and the mean expression was compared between the groups with and without relapse. Results: Expression of 41 miRs correlated with MFS in Cox regression analysis and 21 of these showed different level in pts with and without relapse in the t-Student test (both at p<0.05 level). The top prognostic miRs included miR-99a* (p=0.006), miR-1255B (p=0.005), miR-1233 (p=0.013) and miR-1303 (p=0.03); all previosly shown to be prognostic in AC or NSCLC. We also found 14 new microRNAs (patent pending) potentially prognostic for relapse in AC. Conclusions: Expression of selected miRs may aid in prediction of distant relapse in AC pts undergoing pulmonary resection.

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