Carboxypeptidase E mRNA: Overexpression predicts recurrence and death in lung adenocarcinoma cancer patients

2021 ◽  
pp. 1-9
Author(s):  
I-Ying Kuo ◽  
Danping Liu ◽  
Wu-Wei Lai ◽  
Yi-Ching Wang ◽  
Y. Peng Loh

BACKGROUND: Effective biomarkers for prediction of recurrence of lung adenocarcinoma cancer (LADC) patients are needed to determine treatment strategies post-surgery to improve outcome. OBJECTIVE: This study evaluates the efficacy of carboxypeptidase E (CPE) mRNA including its splice isoforms, CPE-ΔN, as a biomarker for predicting recurrence in adenocarcinoma patients. METHODS: RNA was extracted from resected tumors from 86 patients with different stages of non-small cell LADC. cDNA was synthesized and qRT-PCR carried out to determine the copy numbers of CPE/CPE-ΔN mRNA. Patients were followed for 7 years post-tumor resection to determine recurrence and death. RESULTS: ROC curve analysis showed the overall AUC for CPE/CPE-ΔN copy number was 0.563 in predicting recurrence and 0.563 in predicting death. Kaplan-Meier survival analysis showed statistical difference (p= 0.018), indicating that patients with high CPE/CPE-ΔN copy numbers had a shorter time of disease-free survival and also shorter time to death (p= 0.035). Subgroup analyses showed that association of disease-free survival time with CPE/CPE-ΔN copy number was stronger among stage I and II LADC patients (p= 0.047). CONCLUSIONS: CPE/CPE-ΔN mRNA is a potentially useful biomarker for predicting recurrence and death in LADC patients, especially in identifying patients at high risk of recurrence at early stages I and II.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 710
Author(s):  
Francesco Petrella ◽  
Monica Casiraghi ◽  
Davide Radice ◽  
Andrea Cara ◽  
Gabriele Maffeis ◽  
...  

Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. Results: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30–3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33–4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65–23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44–32.2, p < 0.001). Conclusion: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement.


2020 ◽  
Vol 58 (5) ◽  
pp. 888-898
Author(s):  
Donglai Chen ◽  
Yiming Mao ◽  
Qifeng Ding ◽  
Wei Wang ◽  
Feng Zhu ◽  
...  

Abstract OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P &lt; 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23–34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.


2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3677
Author(s):  
Francesco Petrella ◽  
Monica Casiraghi ◽  
Davide Radice ◽  
Elena Prisciandaro ◽  
Stefania Rizzo ◽  
...  

Background: Red blood cell distribution width is a measure of the variation of erythrocyte volume and has recently been advocated as a prognostic tool in neoplastic and non-neoplastic diseases. We studied the prognostic role of preoperative red blood cell distribution width (RDW) in resected pN1 lung adenocarcinoma patients. Methods: Sixty-seven consecutive pN1 lung adenocarcinoma patients operated in the last two years were retrospectively evaluated in the present study. Age, sex, smoking status, type of surgical resection, neoadjuvant and adjuvant treatments, pathological stage, T and N status, tumor size, preoperative hemoglobin (Hb) and RDW, preoperative neutrophils, lymphocytes, and their ratio were collected for each patient. Outpatient follow-up was performed and date of relapse was recorded. Results: There were 24 females (35.8%). Twenty-eight patients (41.8%) belonged to stage 3A and thirty-nine patients (58.2%) to stage 2B. Mean preoperative RDW % was 14.1 (IQR: 12.9–14.8). Univariate analysis disclosed preoperative RDW as strictly related to disease-free survival (p = 0.02), which was confirmed in the exploratory multivariable analysis (p = 0.003). Conclusions: Pre-operative RDW is an effective prognostic factor of disease-free survival in resected pN1 lung adenocarcinoma; it could therefore be considered as a further tool for planning postoperative adjuvant treatments and setting up an adequate follow-up program.


2011 ◽  
Vol 29 (25) ◽  
pp. 3435-3442 ◽  
Author(s):  
Shinsheng Yuan ◽  
Sung-Liang Yu ◽  
Hsuan-Yu Chen ◽  
Yi-Chiung Hsu ◽  
Kang-Yi Su ◽  
...  

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.


2013 ◽  
Vol 19 (24) ◽  
pp. 6842-6852 ◽  
Author(s):  
Ernest Nadal ◽  
Guoan Chen ◽  
Marc Gallegos ◽  
Lin Lin ◽  
Daysha Ferrer-Torres ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Osugi ◽  
Yuka Kimura ◽  
Yuki Owada ◽  
Takuya Inoue ◽  
Yuzuru Watanabe ◽  
...  

Objective. The aim of this study was to investigate the prognostic value ofMicroRNA-210(miR-210) expression in patients with non-small-cell lung cancer (NSCLC).Methods. We examined themiR-210expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship betweenmiR-210expression and clinicopathological factors as well as histological subtype was statistically analyzed.Results.miR-210expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found betweenmiR-210expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated thatmiR-210expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma.Conclusions. We showed thatmiR-210may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma.


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