scholarly journals Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal

2020 ◽  
Author(s):  
Dawei Yang ◽  
Xiaofang Yang ◽  
Yang Li ◽  
Peige Zhao ◽  
Rao Fu ◽  
...  

Abstract Background Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain. Methods Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes. Results LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 164 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA and LB groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI = 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC. Conclusions These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.

2020 ◽  
Author(s):  
Dawei Yang ◽  
Xiaofang Yang ◽  
Yang Li ◽  
Peige Zhao ◽  
Rao Fu ◽  
...  

Abstract Background: Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain. Methods: Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes. Results: LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC before surgery. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 147 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA (LC patients after surgery) and LB (LC patients before surgery) groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI = 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC. Conclusions: These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.


Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.


2020 ◽  
Vol Volume 13 ◽  
pp. 1931-1939 ◽  
Author(s):  
Guo-Chen Duan ◽  
Xiao-Peng Zhang ◽  
Hui-En Wang ◽  
Zhi-Kang Wang ◽  
Hua Zhang ◽  
...  

2016 ◽  
Vol 151 (3) ◽  
pp. 852-858 ◽  
Author(s):  
Rishindra M. Reddy ◽  
Vasudha Murlidhar ◽  
Lili Zhao ◽  
Svetlana Grabauskiene ◽  
Zhuo Zhang ◽  
...  

2020 ◽  
Vol Volume 12 ◽  
pp. 841-854 ◽  
Author(s):  
Yutong He ◽  
Jin Shi ◽  
Bernd Schmidt ◽  
Qingyi Liu ◽  
Gaofeng Shi ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1750 ◽  
Author(s):  
de Miguel-Pérez ◽  
Bayarri-Lara ◽  
Ortega ◽  
Russo ◽  
Moyano Rodriguez ◽  
...  

Background: The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. Thus, there is an urgent need to identify novel prognostic and predictive biomarkers. Lung adenocarcinoma has distinct clinical–pathological characteristics and novel therapeutic strategies are under active evaluation in the adjuvant setting. Here, we investigated the prognostic impact of circulating tumor cells (CTCs) and gene and miRNA tissue expression in resectable NSCLC. Patients and methods: We assessed the association between CTC subpopulations and the outcome of resected early stage lung adenocarcinoma (ADC) patients at three different time-points (CTC1-3) (before surgery, after one month, and after six months) in comparison to squamous cell carcinoma (SCC). Furthermore, gene and miRNA tissue expression, immunoprofiling, and epithelial-to-mesenchymal transition (EMT) markers were correlated with outcome. Results: ADC (n = 47) and SCC (n = 50) revealed different tissue expression profiles, resulting in the presence of different CTC subpopulations. In ADC, miR-155 correlated with AXL and IL6R expression, which were related to the presence of EMT CTC1 (p = 0.014 and p = 0.004). In the multivariate analysis, CTC2 was an independent prognostic factor for relapse-free survival, and CTC3 and AXL were independent prognostic for overall survival only in ADC. Neither the surgery nor the adjuvant treatment influenced the prognosis of these patients. Conclusions: Our study elucidate the prognostic impact of tissue AXL expression and the presence of CTCs after surgery in adenocarcinoma patients. Tissue AXL expression and CTC EMT activation could potentially represent biomarkers for the stratification of ADC patients that might benefit from new adjuvant therapies.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3012
Author(s):  
Naseer Ahmed ◽  
Biniam Kidane ◽  
Le Wang ◽  
Zoann Nugent ◽  
Nataliya Moldovan ◽  
...  

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.


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