scholarly journals Effect of Napsin A and Circulating Tumor Cells with Mesenchymal Phenotype in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Yu Hong Wei ◽  
yi Zhi He
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Stage ◽  
Free Survival ◽  
Mesenchymal Phenotype ◽  
Napsin A ◽  
Tumor Tissues ◽  
Positive Rate ◽  
Degree Of Differentiation

Abstract Objective: To evaluate the clinical significance of Napsin A and circulating tumor cells（CTCs）with mesenchymal phenotype (M-CTC) in lung adenocarcinoma(LUAD).Materials and Methods: Clinical data of 97 LUAD patients were retrieved. The CanPatrolTM CTC enrichment platform was used to isolate CTCs from the peripheral blood of LUAD patients. The protein expression of Napsin A in the tumor tissues was analyzed by immunohistochemistry. Results: 20 of the 97 patients (20.62%) were negative expression of Napsin A （Napsin A-）and 60 (61.86%) were M-CTC positive（M-CTC+). Both Napsin A expression (P=0.004) and M-CTC+ (P<0.001) showed significant correlation to lymphatic metastasis, and M-CTC+ was also significantly correlated with the tumor stage (P=0.009) but was not correlated with gender, age, smoking, tumor size and degree of differentiation. Furthermore, the Napsin A- patients had a higher positive rate of M-CTC. In addition, the recurrence-free survival (RFS; Log-rank P <0.001) and overall survival (OS; Log-rank P <0.001) of the M-CTC+ LUAD patients were significantly worse. Likewise, Napsin A- was also associated with poor RFS (Log-rank P <0.001) and OS (Log-rank P = 0.0003).Conclusion: LUAD patients with Napsin A- have a higher frequency of M-CTC+, and the Napsin A- and M-CTC+ status portends poor prognosis.

Consistency evaluation of lung adenocarcinoma tissue and circulating tumor cells related gene mutation detection based on multi-site immunomagnetic beads

2022 ◽  
pp. 088532822110658
Author(s):  
Keying Xue ◽  
Bingqing Luo ◽  
Xiaoqing Li ◽  
Weixian Deng ◽  
Chunyan Zeng ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Targeted Therapies ◽  
Sanger Sequencing ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Separation System ◽  
Tumor Tissues

This study was designed to investigate the feasibility of genetic testing using circulating tumor cells (CTCs) instead of tumor tissues in lung adenocarcinoma to break through its limitation. Separation system for epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and Vimentin expressing CTCs was constructed and used to capture CTCs in the blood samples of 57 patients with lung adenocarcinoma. Genetic mutations of genes involved in targeted therapies were detected by next-generation sequencing (NGS) in tissues from these patients. Blood CTC samples with the gene mutations identified by tissue-NGS were selected and corresponding gene mutations were detected by Sanger sequencing. The specificity of the CTC separation system was 95.48% and the sensitivity was 90.85%. The average number of CTCs in the blood of patients with lung adenocarcinoma was 12.47/7.5 mL. Comparison of the tissue-NGS with the CTC-Sanger sequencing showed that the consistencies of genetic mutations of EGFR ( n = 24), KRAS ( n = 9), TP53 ( n = 19), BRAF ( n = 1), ERBB2 ( n = 2), and PIK3CA ( n = 3) were 92.31%, 75.00%, 86.36%, 50.00%, 66.67%, and 75.00%, with an overall consistency of 84.06%. The CTC separation system established in this study shows high specificity and sensitivity. CTCs can be used as a suitable alternative to tumor tissues that are difficult to obtain in clinical practice and overcome the difficulties in tumor tissue collection, which is of significance in guiding clinical medication and individualized treatment with significant clinical application value in terms of genetic testing for targeted therapies in tumor treatment.

EML4-ALK-gene rearrangement comparative analysis in circulating tumor cells and in tumor tissue of patients with lung adenocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7591-7591
Author(s):  
Marius Ilie ◽  
Elodie Long ◽  
Catherine Butori ◽  
Veronique Hofman ◽  
Celine Coelle ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Gene Rearrangement ◽  
Alk Rearrangement ◽  
Molecular Subgroup ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Gene Status

7591 Background: The implementation of new theranostic biomarkers in Oncology is leading to impressive therapeutic improvements. In patients with lung cancer, the possibility to use Circulating Tumor Cells (CTCs) as a non-invasive theranostic approach is a clinically appealing challenge. Adenocarcinomas with EML4-ALK rearrangement are a new molecular subgroup of lung tumors with very good response to Crizotinib, an ALK inhibitor. We have thus aimed at developing an informative assay characterizing the ALK-gene status in CTCs isolated from patients with lung cancer. Methods: CTCs were isolated preoperatively using Isolation by Size of Epithelial Tumor cells method (ISET) from 65 patients with lung adenocarcinoma and blindly screened for ALK-gene status. ALK break-apart fluorescence in situ hybridization (FISH) (LSI ALK dual colour probes set) and immunochemistry using an anti-ALK antibody (5A4 clone) were blindly performed on CTCs and corresponding tumor tissues and results were compared. Results: Two patients consistently showed ALK-gene rearrangement and strong ALK protein expression in CTCs and corresponding tumor samples. Negative results (both ALK FISH and ALK immunochemistry) were found in CTCs and corresponding tumor samples from the other 63 patients. Conclusion: We have developed an approach allowing to characterize ALK-gene status in CTCs from patients with lung cancer and shown consistent results in CTC and tumor tissues. These preliminary results encourage larger studies and open new avenues for non-invasive, real-time, theranostic monitoring of cancer patients.

Isolation of Circulating Tumor Cells of Ovarian Cancer by Transferrin Immunolipid Magnetic Spheres and Its Preliminary Clinical Application

Nano LIFE ◽  
2019 ◽  
Vol 09 (01n02) ◽  
pp. 1940001 ◽  
Author(s):  
Li Zuo ◽  
Wei Niu ◽  
Anqi Li
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Free Survival ◽  
Magnetic Spheres ◽  
Positive Rate

Circulating tumor cells (CTCs) play an important role in cancer prognosis, treatment monitoring and metastasis diagnosis. However, due to the extremely low concentration of CTC in the peripheral blood, its isolation and enrichment are critical steps for early diagnosis. Herein, we used the transferrin modified lipid magnetic spheres for the isolation of ovarian cancer CTCs, and studied the relationship between the CTCs count and the clinical case parameters, prognosis of ovarian cancer. The result showed that no CTC was found in the peripheral blood of 30 patients with benign cysts, and 34 out of 46 patients with ovarian cancer were positive for CTC, with a positive rate of 73.9%. Analysis of the parameters of the clinical cases showed that the positive rate of CTC was related to the clinical stages, and that it was not significantly related to the age, histopathological types and pathological grades of patients. Of the 34 CTC-positive patients, 18 had progression-free survival, with a survival rate of 52.9%, and of the 11 CTC-negative patients, 9 had progression-free survival, with a survival rate of 81.8%. The results showed that the transferrin lipid magnetic spheres prepared in this study, could effectively isolate the CTCs in the peripheral blood of patients with ovarian cancer, that the level of CTC in ovarian cancer patients was related to its clinical stage, and that the progression-free survival of the patients with a high level of CTCs was relatively short. Therefore, this study shows that the transferrin lipid magnetic sphere can achieve effective isolation of ovarian cancer CTC, which can be used as an auxiliary diagnostic method in comprehensive diagnosis of ovarian cancer.

scholarly journals Circulating Tumor Cells and Cancer Stem Cells: Clinical Implications in Nonmetastatic Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40856 ◽  
Author(s):  
M. Sayed ◽  
A.M. Zahran ◽  
M.S.F. Hassan ◽  
D.O. Mohamed
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Overall Survival ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Third ◽  
Disease Free

Purpose Despite the therapeutic advances, disease recurrence remains an ever-present threat to the health and well-being of breast cancer survivors. Assessment of circulating tumor cells (CTCs) and cancer stem cells (CSCs) during and after treatment may be of value in refining treatment. Methods Three 5 mL blood samples were taken from each patient: the first, at diagnosis; the second, after completion of neoadjuvant anthracyclin-based chemotherapy; and the third, a month after surgery and completion of adjuvant radiotherapy. The absolute numbers of CTCs were identified as CD45-cytokeratin+ cells. CTCs per 5 mL of blood were determined by recording all events in the whole suspension. CSCs were identified as cytokeratin+CD44+CD24-/CD45- cells. The CSCs were expressed as a percentage of CTCs. Results Univariate analysis identified the measurements of baseline CTCs and CSCs, taken after chemotherapy and one month after the cessation of radiotherapy, as prognostic factors for both four-year disease-free survival and four-year overall survival. Multivariable analysis identified the third measurement of CSCs, taken one month after the completion of radiotherapy, as the only independent prognostic factor for the four-year disease-free survival (P < 0.002, hazard ratio [HR] = 1.231, 95% CI 1.077–1.407). The initial CTC measurement was the one factor that reached significance on multivariate analysis (P < 0.03, HR 1.969, 95% CI 1.092–3.551) for the four-year overall survival. Correlation was higher between CTC and CSC counts at diagnosis ( r = 0.654, P < 0.001) than after chemotherapy ( r = 0.317, P < 0.03), because of the more rapid decrease in the mean CTC count with chemotherapy. Conclusion The CTC count could be suitable as one of the measures for monitoring response to chemotherapy, while persistence of CSC after cessation of the treatment of nonmetastatic breast cancer, except hormonal therapy when indicated, may be a reason to consider additional therapy in the future. These findings need confirmation in larger randomized trials.

scholarly journals Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors

2020 ◽  
Author(s):  
Dalvinder Mandair ◽  
Mohid S Khan ◽  
Andre Lopes ◽  
Luke Furtado O’Mahony ◽  
Leah Ensell ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Multivariate Logistic Regression Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Optimum Threshold

Abstract Background Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. Objective This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. Patients and Methods CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. Results The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P &lt; .01) for PanNETs and 5.88 (P &lt; .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P &lt; .03) and 5.09 (P &lt; .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P &lt; .01), whereas 2 or greater CTCs had an HR of 2.25 (P &lt; .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P &lt; .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P &lt; .06). Conclusions The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.

Elevated expression of ASF1B correlates with poor prognosis in human lung adenocarcinoma

2021 ◽  
Vol 18 (2) ◽  
pp. 115-127
Author(s):  
Zhenxing Feng ◽  
Jiao Zhang ◽  
Yafang Zheng ◽  
Qingzhang Wang ◽  
Xiaochuan Min ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Development ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Aberrant Expression ◽  
Free Survival ◽  
Advanced Tumor

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.

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