Folate-receptor-positive circulating tumor cells as an efficacious biomarker for the diagnosis of small pulmonary nodules

Yang, Xue; Xie, Shenglong; Shu, Jing; Feng, Gang; Gao, Hong

doi:10.4103/jcrt.jcrt_905_17

Cited by 19 publications

(4 citation statements)

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“…The negative enrichment and LT-PCR based FR + CTC detection has proven a sensitive method for CTC analysis in peripheral blood, with sensitivity of 70-90% for different stages of NSCLC (10,11,17,40). Previous studies have also demonstrated that the FR + CTC is associated with tumor invasiveness and risk of recurrence for resectable NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

Pan

et al. 2021

Front. Oncol.

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BackgroundSurgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FR+CTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.MethodsIn this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FR+CTC analysis. FR+CTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FR+CTC level and the prognosis in these patients was evaluated.ResultsOverall, preoperative FR+CTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes (P = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FR+CTC level was significantly different (P = 0.028). Further, patients with lower preoperative FR+CTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FR+CTC level (RFS: not reached vs. 33.3 months, P = 0.018; OS: not reached vs. 72.0 months, P = 0.13). In a multivariate COX regression analysis, FR+CTC level (HR = 4.10; 95% CI, 1.23–13.64; P=0.022) and pathological stage (HR = 3.16; 95% CI, 1.79–10.14; P = 0.0011) were independent prognostic factors of RFS. Moreover, FR+CTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FR+CTC or adenocarcinoma subtype alone.ConclusionOur study demonstrated that the preoperative FR+CTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FR+CTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.

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Section: Discussionmentioning

confidence: 99%

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

Pan

et al. 2021

Front. Oncol.

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“…CTCs were evaluated using the CytoploRare method (GenoSaber Biotech Co., Ltd., China) 16 , 17 . Blood (~3 ml) was collected from participants 1-2 days before surgery.…”

Section: Methodsmentioning

confidence: 99%

“…Blood (~3 ml) was collected from participants 1-2 days before surgery. Erythrocytes were removed by red blood cell lysis, and CD45+ leukocytes were depleted using magnetic beads 16 , 17 . CTCs were stained with the BCAR1 antibody ( Table S2 ) and analyzed.…”

Section: Methodsmentioning

confidence: 99%

BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma

Mao¹,

Jiang²,

Wang³

et al. 2021

Int. J. Biol. Sci.

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Background:We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-tomesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.

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“…High expression of FR-a was found in 12%-50.5% of endometrioid cancers, 33%-41% of serous cancers, and 25% of clear cell cancers (14)(15)(16)(17). Based on the different expression of FR-a, antibody drugs targeting FR-a have been developed previously (10,(18)(19)(20)(21)(22). Results of a combination of folic acid and high-density lipoprotein fluorescent nanoparticles showed that with the linking of folic acid, the uptake of fluorescent nanoparticles in ovarian cancer tissues significantly increased, which is an excellent targeted drug (23).…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions

et al. 2021

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The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.

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Folate-receptor-positive circulating tumor cells as an efficacious biomarker for the diagnosis of small pulmonary nodules

Cited by 19 publications

References 0 publications

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients

BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma

Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions

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