Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma

Abstract Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR)-sensitizing mutation could significantly improve prognosis in patients with LUAD. Here, we aimed to elucidate the prognostic value of NDRG2 combined with EGFR-sensitizing mutations in patients with LUAD. Methods: Lung parenchyma specimens obtained during surgery or CT-guide percutaneous lung puncture biopsy for the NDRG2 protein and EGFR genomic testing were obtained. Associations between NDRG2/EGFR and clinicopathological characteristics of patients with LUAD were extracted from the Tianjin First Central Hospital in China between June 2013 and June 2014. Results: The expression of NDRG2 was significantly decreased in patients with LUAD. Expressions of NDRG2 and EGFR-sensitizing mutations showed positive correlations with survival. Expression of NDRG2 and EGFR-sensitizing mutations were associated with the longer overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Advanced stages were significantly associated with low expression of NDRG2. In multivariate analysis, compared with other patients, NDRG2 (+)/EGFR (+) was independently associated with prolonged OS and PFS. Conclusion: NDRG2 combined with EGFR-sensitizing mutations might be valuable markers to evaluate the prognosis of LUAD patients.

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Prognostic significance of NDRG2 combined with EGFR-sensitizing mutations in lung adenocarcinoma

10.21203/rs.2.14181/v5 ◽

2020 ◽

Author(s):

Bo Yang ◽

Linlin Ji ◽

Yiling Feng ◽

Xiao-Ping Li ◽

Hong-Gang Zhou ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Progression Free Survival ◽

Lung Parenchyma ◽

Diagnostic Value ◽

Clinicopathological Characteristics ◽

Free Survival ◽

Lung Puncture

Abstract Background: N-myc downstream-regulated gene 2 (NDRG2) plays a substantial role in lung adenocarcinoma (LUAD). Epidermal growth factor receptor (EGFR)-sensitizing mutation could significantly improve prognosis in patients with LUAD. Here, we aimed to elucidate the prognostic value of NDRG2 combined with EGFR-sensitizing mutations in patients with LUAD. Methods: Lung parenchyma specimens obtained during surgery or CT-guide percutaneous lung puncture biopsy for the NDRG2 protein and EGFR genomic testing were obtained. Associations between NDRG2/EGFR and clinicopathological characteristics of patients with LUAD were extracted from the Tianjin First Central Hospital in China between June 2013 and June 2014. Results: The expression of NDRG2 was significantly decreased in patients with LUAD. Expressions of NDRG2 and EGFR-sensitizing mutations showed positive correlations with survival. ROC curve analyses showed that the diagnostic value of NDRG2 combined with EGFR in LUAD was significantly higher than that of each biomarker alone. Expression of NDRG2 and EGFR-sensitizing mutations were associated with the longer overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Advanced stages were significantly associated with low expression of NDRG2. In multivariate analysis, compared with other patients, NDRG2 (+)/EGFR (+) was independently associated with prolonged OS and PFS. Conclusion: NDRG2 combined with EGFR-sensitizing mutations might be valuable markers to evaluate the prognosis of LUAD patients.

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The Prognostic Significance of Combined Pretreatment Fibrinogen and Neutrophil-Lymphocyte Ratio in Various Cancers: A Systematic Review and Meta-Analysis

Disease Markers ◽

10.1155/2020/4565379 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Rongqiang Liu ◽

Shiyang Zheng ◽

Qing Yuan ◽

Peiwen Zhu ◽

Biao Li ◽

...

Keyword(s):

Prognostic Value ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

Regression Analyses ◽

Free Survival ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Meta Regression

Purpose. The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. Methods. An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. Results. Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS ( HR = 1.77 ; 95% CI, 1.51–2.08) and poor DFS/PFS ( HR = 1.63 ; 95% CI, 1.30–2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. Conclusions. Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.

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Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽

10.3390/cancers10110434 ◽

2018 ◽

Vol 10 (11) ◽

pp. 434 ◽

Cited By ~ 4

Author(s):

Ming-Ju Tsai ◽

Jen-Yu Hung ◽

Mei-Hsuan Lee ◽

Chia-Yu Kuo ◽

Yu-Chen Tsai ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Stage Iv ◽

Progression Free Survival ◽

Egfr Mutations ◽

First Line ◽

Free Survival ◽

Younger Patients ◽

Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

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Clustered Genomic Alterations in Chromosome 7p Dictate Outcomes and Targeted Treatment Responses of Lung Adenocarcinoma With EGFR-Activating Mutations

Journal of Clinical Oncology ◽

10.1200/jco.2011.35.3979 ◽

2011 ◽

Vol 29 (25) ◽

pp. 3435-3442 ◽

Cited By ~ 24

Author(s):

Shinsheng Yuan ◽

Sung-Liang Yu ◽

Hsuan-Yu Chen ◽

Yi-Chiung Hsu ◽

Kang-Yi Su ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Kinase Inhibitors ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Comparative Genomic ◽

Wild Type ◽

Free Survival ◽

Activating Mutation ◽

Disease Free ◽

Egfr Tkis

Purpose Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation. Patients and Methods We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs. Results We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation. Conclusion Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population.

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The Prognostic Roles and Clinical Features of CD44v9 in Human Solid Cancers—A Meta-Analysis

10.21203/rs.3.rs-54020/v1 ◽

2020 ◽

Author(s):

Yuanxiu Deng ◽

Jie Wang ◽

Shenhui Ji ◽

Lu Huang ◽

Meijiang Feng

Keyword(s):

Clinical Features ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

High Expression ◽

Cochrane Library ◽

Cancer Specific Survival ◽

Free Survival ◽

Diagnosis And Prognosis

Abstract Background: CD44 is the primary receptor for hyaluronic acid and serves as a marker for cancer stem cells. CD44v9 is one of CD44’s variants and takes part in cancer’s growth and metastasis. However, the prognostic roles and clinical features of CD44v9 in cancers remain unclear. Therefore, we conducted this meta-analysis to summarize the prognostic significance and clinical features of CD44v9 in human solid cancers.Methods: we systematically searched all of related studies in PubMed, the Web of Science, Embase and Cochrane library up to June 2020. We analyzed the pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to assess the prognostic functions and clinical features of CD44v9 in various human solid cancers.Results: In this meta-analysis, we included 1705 cancer patients among 12 studies. Results indicated that high expression of CD44v9 was significantly related to poorer overall survival (OS) (HR=1.60, 95%CI 1.28-1.99, P<0.0001), recurrence-free survival/progression-free survival/disease-free survival (RFS/PFS/DFS).( HR=1.81, 95%CI 1.16-2.84, P=0.009) and disease-specific survival/cancer-specific survival (DSS/CSS) (HR=2.93, 95%CI 1.69-5.10, P<0.001). At the same time, we also found that high expression of CD44v9 increased the possibility of lymphoid infiltrates (OR=1.59, 95%CI 1.16-2.20, P=0.005), vascular invasion (OR=1.57, 95%CI 1.11-2.22, P=0.010) and higher TNM stage (OR=1.63, 95%CI 1.19-2.23, P=0.002).Conclusion: Our results demonstrate that CD44v9 overexpression is associated with worse OS, RFS/PFS/CFS and DSS/CSS in patients with solid cancers, which might be a biomarker in the diagnosis and prognosis of cancers in the future.

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Prognostic value of circulating tumor cells in patients with bladder cancer: A meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0254433 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254433

Author(s):

Hui Jiang ◽

Xiujuan Gu ◽

Zhihua Zuo ◽

Gang Tian ◽

Jinbo Liu

Keyword(s):

Bladder Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

Free Survival ◽

Number Of Patients ◽

Registration Number

Background Circulating tumor cells (CTCs) have been considered diagnostic and prognostic biomarkers for urothelial cancer. However, the prognostic role of CTCs in bladder cancer (BC) remains controversial. Here, we conducted a meta-analysis to evaluate the prognostic significance of CTCs for patients with BC. Methods All studies relevant to this topic were searched in the PubMed, Embase, and Web of Science databases. The hazard ratio (HR) and 95% confidence interval (95% CI) were set as effect measures. The outcomes were overall survival (OS), cancer-free survival (CSS), progression-free survival (PFS)/time to progression (TTP), and disease-free survival (DFS)/recurrence-free survival (RFS)/time to first recurrence (TFR). All analyses were conducted in STATA 15.1. Results Eleven eligible studies comprising 1,062 patients with BC were included in this meta-analysis. Overall analyses showed that CTC-positive patients had poorer survival (OS: HR 3.88, 95% CI 2.52–5.96, p < 0.001; CSS: HR 3.89, 95% CI 2.15–7.04, p < 0.001) and more aggressive progression (PFS/TTP: HR 5.92, 95% CI 3.75–9.35, p < 0.001; DFS/RFS/TFR: HR 4.57, 95% CI 3.34–6.25, p < 0.001) than CTC-negative patients. Subgroup analyses according to the number of patients, detection method, positivity rate, and follow-up time revealed that the presence of CTCs predicted a high risk of mortality and disease progression in most subgroups. Conclusion The meta-analysis confirmed that CTCs are a promising prognostic biomarker of poor survival and aggressive tumor progression for patients with BC. Prospero registration number CRD42021224865.

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The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.712760 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wen-Long Guan ◽

Yue Ma ◽

Yue-Hong Cui ◽

Tian-Shu Liu ◽

Yan-Qiao Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Mismatch Repair ◽

Disease Free Survival ◽

Progression Free Survival ◽

Clinicopathological Characteristics ◽

Her2 Status ◽

Clinical Role ◽

Record System ◽

Free Survival ◽

The Impact

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

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Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer

The International Journal of Biological Markers ◽

10.1177/1724600820955195 ◽

2020 ◽

Vol 35 (4) ◽

pp. 20-27 ◽

Cited By ~ 1

Author(s):

Enrico Potenza ◽

Giulia Parpinel ◽

Maria E. Laudani ◽

Chiara Macchi ◽

Luca Fuso ◽

...

Keyword(s):

Ovarian Cancer ◽

Predictive Value ◽

Prognostic Significance ◽

Disease Free Survival ◽

Progression Free Survival ◽

Serum Levels ◽

Ca 125 ◽

Free Survival ◽

The Third ◽

Response To Chemotherapy

Introduction: At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. Methods: We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016–2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Results: Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). Conclusions: We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

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Immunophenotyping of ampullary carcinomata allows for stratification of treatment specific subgroups

Journal of Clinical Pathology ◽

10.1136/jclinpath-2015-203337 ◽

2015 ◽

Vol 69 (5) ◽

pp. 431-439 ◽

Cited By ~ 10

Author(s):

Joyce M Leo ◽

Steve E Kalloger ◽

Renata D Peixoto ◽

Nadia S Gale ◽

Douglas L Webber ◽

...

Keyword(s):

Prognostic Significance ◽

Progression Free Survival ◽

Clinicopathological Characteristics ◽

Ductal Adenocarcinoma ◽

Histological Subtype ◽

Regional Lymph Nodes ◽

Free Survival ◽

Treatment Regimens ◽

Molecular Differentiation ◽

Prognostic Groups

BackgroundAmpullary carcinomata (AC) can be separated into intestinal (IT) or pancreatobiliary (PB) subtypes. Although morphological, immunohistochemical and molecular differentiation of IT and PB have been well documented; the prognostic significance of histological subtype and whether patients with either subtype benefit from differential chemotherapeutic regimens remains unclear.MethodsAs part of a larger cohort study, patients who underwent resection for AC or pancreatic ductal adenocarcinoma (PDAC) were retrospectively identified. Clinicopathological covariates and outcome were obtained and MUC1, MUC2, CDX2 and CK20 were assessed with immunohistochemistry.ResultsOf 99 ACs, the resultant immunophenotypes indicated 48% and 22% were IT and PB, respectively. Thirty (30%) cases were quadruple negative (QN). Within the PDAC cohort (N=257), the most prevalent immunophenotype was QN (53%). Subsequently, all QN ACs were classified as PB immunohistochemically yielding 47.5% and 52.5% classified as IT and PB, respectively. Involved regional lymph nodes and elevated T-stage were significantly associated with PB compared with IT AC (p=0.0032 and 0.0396, respectively). Progression-free survival revealed inferior survival for PB versus IT AC (p=0.0156).ConclusionsAC can be classified into prognostic groups with unique clinicopathological characteristics using immunohistochemistry. Immunophenotypical similarity of PB and PDAC suggests that treatment regimens similar to those used in PDAC should be explored.

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Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer

Bioscience Reports ◽

10.1042/bsr20193286 ◽

2020 ◽

Vol 40 (2) ◽

Author(s):

Mingdi Zhang ◽

Hongliang Chen ◽

Maoli Wang ◽

Fang Bai ◽

Kejin Wu

Keyword(s):

Breast Cancer ◽

Bioinformatics Analysis ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Predictive Biomarker ◽

Expression Level ◽

Relapse Free Survival ◽

Free Survival ◽

Metastatic Relapse

Abstract Background: Collagen type X alpha 1 (COL10A1) is overexpressed in diverse tumors and displays vital roles in tumorigenesis. However, the prognostic value of COL10A1 in breast cancer remains unclear. Methods: The expression of COL10A1 was analyzed by the Oncomine database and UALCAN cancer database. The relationship between COL10A1 expression level and clinical indicators including prognostic data in breast cancer were analyzed by the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results: COL10A1 was up-regulated in different subtypes of breast cancer. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) status and nodal status were positively correlated with COL10A1 expression. Conversely, age, the Scarff–Bloom–Richardson (SBR) grade, basal-like status, and triple-negative status were negatively related to COL10A1 level in breast cancer samples compared with normal tissues. Patients with increased COL10A1 expression level showed worse overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). COL10A1 was positively correlated with metastatic relapse-free survival. GSEA analysis revealed that enrichment of TGF-β signaling pathway. 15-leucine-rich repeat containing membrane protein (LRRC15) is a correlated gene of COL10A1. Conclusion: Bioinformatics analysis revealed that COL10A1 might be considered as a predictive biomarker for prognosis of breast cancer. Further experiments and clinical trials are essential to elucidate the value of COL10A1 in breast cancer treatment.

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