scholarly journals The Role of TOP2A Protein Expression and Aneuploidy in NSCLC

2021 ◽  
Author(s):  
Zhenwen Chen ◽  
Zijuan Zeng ◽  
Qi Wang ◽  
Yanfeng Xi ◽  
Yirong Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Poor Prognosis ◽  
Topoisomerase Ii ◽  
Cox Regression ◽  
Topoisomerase Ii Alpha ◽  
Chi Square ◽  
Kappa Test ◽  
Enhanced Expression ◽  
Nsclc Patients

Abstract Purpose DNA topoisomerase II alpha (TOP2A) is a cell-cycle dependent protein associated with cell proliferation and division. Abnormal regulation of TOP2A and aneuploidy induces tumorigenesis and poor prognosis. Data related to TOP2A protein in non-small cell lung cancer (NSCLC) is limited to few studies on gene status. The present study aimed to investigate the consistency between aneuploidy and expression of TOP2A gene and protein, respectively, and the role of aneuploidy in the prognosis of NSCLC patients. Methods Clinical data and lung cancer tissues were collected from 244 patients with NSCLC. TOP2A protein and gene expression were detected using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Nonparametric Spearman’s rank sum test was used to analyze clinicopathological data. Kaplan–Meier and multivariate Cox regression methods were used for survival analysis. Results Enhanced expression and amplification rate of TOP2A protein and gene were 29.9% (73/244) and 0.4% (1/244), respectively. The aneuploidy rate was 31.6% (77/244). In NSCLC, patients with enhanced expression of TOP2A protein and aneuploidy correlated with clinical stages (p < 0.001) Enhanced expression of TOP2A protein was consistent with aneuploidy as detected by Kappa test (K = 0.307) and this correlation was confirmed by chi-square test (p < 0.001). The overall survival of patients with aneuploidy was shorter than diploidy (p < 0.001). Clinically advanced patients with aneuploidy together with TOP2A overexpression had poor prognosis (p < 0.001). Conclusion Aneuploidy and overexpression of TOP2A is a predictor of poor prognosis in patients with advanced NSCLC.

The role of social determinants on overall survival in advanced-stage non-small cell lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21117-e21117
Author(s):  
Andreas Bello ◽  
Neeharika Srivastava Makani
Keyword(s):  
Lung Cancer ◽  
Social Determinants ◽  
Small Cell ◽  
Financial Assistance ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Chi Square ◽  
Study Population ◽  
Nsclc Patients

e21117 Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer. Many studies have evaluated the association of social determinants with outcomes in early-stage NSCLC. These studies have shown statistically and clinically significant associations between overall survival (OS) and other social factors (e.g marital status, educational attainment). The aim of our study was to better understand the role of various social determinants of health (SDH) on OS in advanced-stage NSCLC patients in a community oncology practice in Florida. Methods: In this retrospective study, 125 patients with stage III and IV NSCLC were recruited between January 1st, 2014 until December 31st, 2018. We performed both categorical and continuous analyses (Pearson’s chi-square and Kruskal-Wallis test, respectively) to evaluate the association between median OS and several independent variables, including; gender, race, marital status, insurance status, living status, receiving financial assistance (FA), alcohol use, and smoking histories. OS is defined as the date of diagnosis up to the date of death. Other confounders that were analyzed included histology, treatment modality, comorbidities, and performance status of the patients. Results: Of the total study population (n = 125), 60% identified as male with a mean age of 73 years for the study population. The majority of patients (89%) identified as white; 56% were married, and 81% lived with someone. 66% of patients had an HMO insurance plan, and 51% of patients obtained FA to help with treatment care costs. 47% of patients identified as former smokers and 54% denied any alcohol use. The median OS for the patient population was 0.756 years. Chi-square analyses revealed that patients who received FA were more likely to live longer than median OS as opposed to patients that did not receive FA (OR = 2.41, 95% CI [1.18, 4.96], p = 0.050). Kruskal-Wallis analyses demonstrated that patients receiving FA had nearly a two-fold increase in median OS compared to patients without financial assistance (median OS = 1.01 years vs. 0.545 years, respectively; p = 0.013). However, other social determinants evaluated did not have a significant impact on relative OS in advanced-stage NSCLC. Conclusions: Ultimately, our study concludes that receiving FA has a significant association with increased OS in advanced-stage NSCLC patients. This study highlights the importance of reducing the financial burden of advanced-stage NSCLC patients and how FA impacts patient outcomes. Future prospective cohort studies with a larger sample size are warranted to identify other SDH, as well as the underlying mechanisms affecting median OS, in patients with advanced-stage NSCLC.

scholarly journals High expression of Aurora-B is correlated with poor prognosis and drug resistance in non-small cell lung cancer

2018 ◽  
Vol 33 (2) ◽  
pp. 215-221 ◽  
Author(s):  
JingJing Yu ◽  
Jing Zhou ◽  
Fei Xu ◽  
Wei Bai ◽  
Wei Zhang
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Poor Prognosis ◽  
Drug Response ◽  
Small Cell ◽  
Aurora B ◽  
Small Cell Lung ◽  
Nsclc Patients

Objective: Aurora kinase B (Aurora-B) is a crucial regulator of accurate mitosis. Abnormal Aurora-B expression is associated with aneuploidy and has been implicated in the pathogenesis and drug resistance in a variety of human cancers. However, little evidence is available regarding the role of Aurora-B in regulating drug response in non-small cell lung cancer (NSCLC), which is the most common type of lung cancer, and is characterized with poor prognosis and high mortality. Method: In the current study, we investigated the association of Aurora-B with the prognosis of NSCLC patients, and we also used the latest CRISPR/Cas9 system to explore the regulatory role of Aurora-B in NSCLC cells developing resistance to cisplatin (CDDP) and paclitaxel. Results: We found that Aurora-B was correlated with significantly reduced overall survival and disease-free survival in NSCLC patients. Aurora-B overexpression was also observed in NSCLC cells developing impaired response to both CDDP and paclitaxel. Moreover, we found, for the first time, that Aurora-B may impair NSCLC drug response by disturbing cell proliferation and inhibiting p53-related DNA damage response and apoptotic pathway, while the knockout of Aurora-B resensitized NSCLC cells to chemo drugs by ensuring correct chromosome segregation and restoring p53 expression. Conclusions: Our results demonstrated the association of Aurora-B with chemoresistance in NSCLC, which may finally contribute to the poor prognosis of NSCLC patients. We also suggested Aurora-B as a promising therapeutic target in NSCLC treatment.

scholarly journals Liquid biopsy in NSCLC: a new challenge in radiation therapy

2021 ◽  
Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Minimum Residual ◽  
Nsclc Patients ◽  
Choice Of Therapy ◽  
Tumor Dna

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.

scholarly journals Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 245 ◽  
Author(s):  
Yosuke Miura ◽  
Noriaki Sunaga
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Direction ◽  
Nsclc Patients

The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

scholarly journals Significance of accurate hilar and intrapulmonary lymph node examination and prognostication in stage IA–IIA non-small cell lung cancer, a retrospective cohort study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wenyu Zhai ◽  
Fangfang Duan ◽  
Yuzhen Zheng ◽  
Qihang Yan ◽  
Shuqin Dai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Survival ◽  
Differentiation Degree ◽  
Stage Ia ◽  
Nsclc Patients

Abstract Background The examination of lymph nodes (LNs) plays an important role in the nodal staging of non-small cell lung cancer (NSCLC). For patients without LN metastasis, the main role of thorough LN examination is accurate staging, which weakens the effect of staging migration. To date, the role of hilar and intrapulmonary (N1) station LNs has not been fully appreciated. In this study, we aimed to confirm the significance of N1 LNs in long-term survival for stage IA–IIA NSCLC patients and to find the minimum number of LN to examine. Methods The data of patients who underwent radical lobectomy and were confirmed as having non-metastatic LNs from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of LNs examined. The Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors. Results The median number of resected N1 LNs was 8. The number of patients with 0–2 N1 LNs, 3–5 N1 LNs, 6–8 N1 LNs, 9–11 N1 LNs, and more than 11 N1 LNs examined was 181, 425, 477, 414, and 531, respectively. Sex (P = 0.004), age (P < 0.001), tumor size (P = 0.004), differentiation degree (P = 0.001), and number of N1 LNs examined (P = 0.008) were independent prognostic factors of overall survival. Gender (P = 0.006), age (P = 0.031), tumor size (P = 0.001), differentiation degree (P = 0.001), vascular invasion (P = 0.034), and number of N1 LNs examined (P = 0.007) were independent prognostic factors of disease-free survival. Compared with patients with 0–5 N1 LNs examined, patients with more than 5 N1 LNs examined had better OS (P = 0.015) and had better DFS (P = 0.015) if only a landmark 5-year follow-up was performed. Conclusion Increasing the number of N1 LN examination might improve the long-term survival of T1-2N0 NSCLC patients. These data indicate that at least 6 N1 nodes examined is an essential part in surgical and pathological management but cannot prove this. This finding should be confirmed in a large, prospective randomized clinical study.

scholarly journals Serum miR-1228-3p and miR-181a-5p as Noninvasive Biomarkers for Non-Small Cell Lung Cancer Diagnosis and Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wei-Xiao Xue ◽  
Meng-Yu Zhang ◽  
Rui Li ◽  
Xiao Liu ◽  
Yun-Hong Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Roc Analysis ◽  
Cox Regression ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Noninvasive Biomarkers ◽  
Nsclc Patients

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.

The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18084-e18084
Author(s):  
Hongbing Liu
Keyword(s):  
Protective Factor ◽  
Cox Regression ◽  
Rank Test ◽  
Small Cell Lung ◽  
Baseline Serum ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Serum Cea ◽  
Nsclc Patients

e18084 Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.

The correlation between immune status of patients and their prognosis in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23192-e23192
Author(s):  
Xiao Ding ◽  
Jiuwei Cui ◽  
Xu Yan ◽  
Chao Niu ◽  
Huimin Tian
Keyword(s):  
Lung Cancer ◽  
Poor Prognosis ◽  
Immune Status ◽  
Serum Samples ◽  
Mhc I ◽  
Expression Levels ◽  
Surface Molecules ◽  
Tnf Α ◽  
Ifn Γ ◽  
Nsclc Patients

e23192 Background: In order to investigate the association of immune status with the prognosis in patients with lung cancer and to screen the potential prognostic markers, the immune status including the expression levels of tumor surface molecules, tumor infiltrating lymphocytes (TIL) and cytokines, sMICA and sMICB in serum were detected in this study. Methods: Tissue and serum samples of 125 patients with NSCLC were obtained from the First Hospital of Jilin Universtiy. 50 serum samples of healthy volunteers were obtained as controls. Surface molecules of cancer cell, such as MHC-I, PD-L1, MICA/B and CD8+ TIL were detected with immunohistochemistry. Cytokines such as IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α levels in serum were detected with Luminex. sMICA and sMICB levels were examined by ELISA. The association between their expression levels and patients’ prognosis was analyzed by SPSS 17.0 software. Results: MHC-I was down-expressed, PD-L1 and MICA/B were up-regulated in NSCLC. CD8+ TIL could be seen in tumor stroma and nest. In univariate analysis, we found that patients with down-expression of MHC-I and up-regulation of PD-L1 had a poor prognosis (P < 0.05). MICA/B expression had no correlation with patients’ prognosis (P > 0.05). Patients with more stromal CD8+ TIL might have better prognosis. In multivariate analysis, we found that MHC-I and stromal CD8+ TIL might be independent prognostic factors in NSCLC (P < 0.05). TNF-α and IFN-γ were significantly decreased, IL-6 was increased in NSCLC patients (P < 0.05). There were no connections between the cytokines levels with patients’ prognosis (P > 0.05). Serum sMICA was significantly higher in NSCLC patients than healthy controls (P < 0.05). sMICB tented to be elevated in NSCLC compared with health controls, but there was no significant difference (P > 0.05). High sMICA expression had an association with poor prognosis (P < 0.05). There was no connection between the sMICB level with patients’ prognosis (P > 0.05). Conclusions: The immune status of patients with NSCLC had a close association with their prognosis in this study. It worths further study to confirm the clinical value of MHC-I expression, stromal CD8+ TIL and serum sMICA as prognostic marker in the patients with NSCLC.

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