Folate Receptor-positive Circulating Tumor Cells Research Articles

Clinical significance of postoperative folate receptor-positive circulating tumor cells (FR + CTCs) for long-term prognosis in patients with invasive adenocarcinoma (IAC) of the lung.

The aim of the study was to evaluate the prognostic value of postoperative folate receptor-positive circulating tumor cell (FR + CTC) detection in patients with stage I-III invasive adenocarcinoma (IAC) treated with surgery. Patients with lung adenocarcinoma (LUAD) who underwent surgical resection in Peking University Cancer Hospital and received postoperative FR + CTC analysis from July 2016 to January 2021 were retrospectively collected. Comparisons between or among groups were made using the Kruskal-Wallis or Mann-Whitney U tests. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression analyses were performed to explore the factors predicting recurrence and survival. There were significant differences between the high and low groups in terms of age (p = 0.002), postoperative CA199 (p = 0.038), and postoperative SCC (p = 0.024). There were no significant differences in the other indicators (all p>0.05). N stage 1, N stage 2, and neoadjuvant therapy (NAT) were independent risk factors for disease recurrence and death; pleural invasion (PI), and nerve invasion were independent risk factors for death. The Kaplan-Meier curve showed a notable trend for a worse disease-free survival (DFS) or overall survival (OS) for patients with high levels of FR + CTCs in our study, but none of these were statistically significant. The detection of FR + CTCs postoperatively was an independent predictor of recurrence in patients treated for stage I-III IAC. Standardized detection methods and optimal time points for assessment should be established in future studies.

Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study

BackgroundThe aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC).MethodsThree ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis.Resultsthere were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51).ConclusionsESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making.Trial registrationThe study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).

885P Clinical significance of folate receptor-positive circulating tumor cells detected by ligand-targeted polymerase chain reaction in nasopharyngeal carcinoma

885P Clinical significance of folate receptor-positive circulating tumor cells detected by ligand-targeted polymerase chain reaction in nasopharyngeal carcinoma

15. EFFECT OF ARTIFICIAL CAPNOTHORAX VS NON-CAPNOTHORAX DURING THORACOSCOPIC ESOPHAGECTOMY ON CIRCULATING TUMOR CELLS AND SURVIVAL IN ESOPHAGEAL CANCER

Abstract Background To investigate the effect of artificial capnothorax on circulating tumor cells and survival after minimally invasive esophagectomy for esophageal cancer. Methods This prospective, multicenter, randomized controlled trial was conducted in a tertiary hospital in China. Between August 2019 and January 2020, 110 patients with resectable esophageal cancer were randomized to undergo non-capnothorax esophagectomy (n = 55) or capnothorax procedures. The analysis was based on the intention-to-treat principle. The final follow-up occurred in November 2022. The main outcomes were changes in folate receptor-positive circulating tumor cells, 3-year overall survival, and disease-free survival rates. Results A total of 110 patients were included in the intention-to-treat analysis. After surgery, the incidence of patients with incremental changes in FR + CTC levels was 18.6% (8/43) in the capnothorax group and 2.7% (1/37) in the non-capnothorax group (P = 0.033) (mean changes, −3.9 ± 3.4 [FU/3 mL] vs −2.4 ± 2.9 [FU/3 mL], respectively; P = 0.039). There were significant differences in the 3-year overall survival rate (81.6% [95%, 72.4–92.0] vs 65.2% [95%, 59.3–78.8]; P = 0.002) and disease-free survival rate (81.6% [95%, 72.4–93.0] vs 61.6% [95%, 50.1–75.7]; P = 0.015) between the two groups. Multivariate analysis indicated that the artificial pneumothorax approach was a prognostic factor for overall survival (HR: 2.347, 95% CI: 1.053–5.235; P = 0.037) and disease-free survival (HR: 1.325, 95% CI: 1.210–1.451; P &amp;lt; 0.001). Conclusions Artificial capnothorax during surgery resulted in increased dissemination of circulating tumor cells and worse survival outcomes in patients with esophageal cancer. Esophagectomy under non-capnothorax should be a recommended procedure.

An integrated and renewable interface for capture, release and analysis of circulating tumor cells

Circulating tumor cells (CTCs) have now emerged as a type of promising circulating biomarkers in liquid biopsy and can predict the occurrence and development of cancers. In this work, an integrated and renewable interface is fabricated for the capture, release and quantitative analysis of CTCs. As designed, folate receptor-positive CTCs are captured by folic acid-modified DNA probes at the interface through the receptor-ligand interaction, and are efficiently released from the interface with the aid of bleomycin-ferrous complex-regulated cleavage. Taking MCF-7 cells as the model, the functional interface demonstrates high efficiency to selectively capture the folate receptor-positive tumor cells, and the bleomycin-ferrous complex-regulated cleavage not only easily releases the captured cells with well-maintained viability and proliferation ability, but also releases silver nanoparticles that are labeled at the cell surface for highly sensitive quantification by adopting electrochemical techniques with a detection limit of 6 cells/mL. At the meanwhile, the interface is proved to be regenerated through a simple cleavage-hybridization event and reused with high stability. Therefore, our work may provide a new idea for the collection and downstream researches of circulating tumor cells in the future.

Preoperative levels of folate receptor-positive circulating tumor cells in different subtypes of early-stage lung adenocarcinoma: Predictive value for determining extent of surgical resection.

The objective was to measure the correlations of preoperative levels of folate receptor-positive circulating tumor cells (FR+CTCs) with clinical characteristics and histologic subtype in early-stage lung adenocarcinoma, and to determine the predictive value of FR+CTC level in preoperative determination of the extent of surgical resection. In this retrospective, single-institution, observational study, preoperative FR+CTC levels were measured via ligand-targeted enzyme-linked polymerization in patients with early-stage lung adenocarcinoma. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff value of FR+CTC level for prediction of various clinical characteristics and histologic subtypes. No significant difference in FR+CTC level was observed among patients with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) (P = 0.813). Within the non-mucinous adenocarcinoma group, no difference was observed among patients with tumors whose predominant growth patterns were lepidic, acinar, papillary, micropapillary, solid, and complex gland (P = 0.053). However, significant differences in FR+CTC level were observed between patients with and without the micropapillary subtype [11.21 (8.22-13.61) vs. 9.85 (7.43-12.63), P = 0.017], between those with and without the solid subtype [12.16 (8.27-14.90) vs. 9.87 (7.50-12.49), P = 0.022], and between those with any of the advanced subtypes (micropapillary, solid, or complex glands) vs. none of these [10.48 (7.83-13.67) vs. 9.76 (7.42-12.42), P = 0.032]. FR+CTC level was also correlated with degree of differentiation of lung adenocarcinoma (P = 0.033), presence of visceral pleural invasion (VPI) of lung carcinoma (P = 0.003), and lymph node metastasis of lung carcinoma (P = 0.035). FR+CTC level is of potential predictive value in determining the presence of aggressive histologic patterns (micropapillary, solid, and advanced subtypes), degree of differentiation, and occurrence of VPI and lymph node metastasis in IAC. Measurement of FR+CTC level combined with intraoperative frozen sections may represent a more effective method of guiding resection strategy in cases of cT1N0M0 IAC with high-risk factors.

The value of folate receptor-positive circulating tumor cells in the diagnosis of lung cancer and its correlation with clinical characteristics.

The aim of this research is to investigate the feasibility of folate receptor-positive circulating tumor cells (FR+CTCs) as a biomarker for the diagnosis of malignant pulmonary nodules and the correlation between clinicopathological factors and FR+CTC levels. Patients initially diagnosed with one or more pulmonary nodules from a computed tomography scan were prospectively included. Three milliliters of peripheral blood was collected from each participant for FR+CTC analysis prior to surgery. Clinical and pathological parameters and FR+CTC levels were compared between patients with lung cancer and benign diseases. Six hundred fifty-three patients had lung cancer and the other 124 had benign lung diseases based on pathological examinations of the resected specimens. The median FR+CTC value of the lung cancer group was 12.0(95% CI 9.6-16.2)FU/3mL and that of the benign group was 7.2(95% CI 5.78-11.2)FU/3mL. The difference was statistically significant (P < 0.0001). In a receiver operating characteristic analysis to distinguish the two groups, the area under curve of FR+CTC was 0.7457 (95% CI 0.6893-0.8021; P < 0.0001) using a cutoff of 8.65 FU/3mL. The sensitivity was 86.37%, and the specificity was 74.19%. Combined with conventional serum tumor biomarkers, the area under curve was 0.922 (0.499-0.963). The sensitivity was 92.20%, and the specificity was 83.05%. FR+CTC levels were related to tumor staging (P4< 0.001), the degree of tumor invasion both in single (P = 0.011) and multiple lesions (P = 0.022), pathological subtypes (P = 0.013), and maximum tumor diameter (P = 0.014). FR+CTC is an effective and reliable biomarker for the diagnosis of lung cancer. Further, FR+CTC level is correlated with tumor staging, degree of invasion, pathological subtypes, and tumor size.

Folate receptor-positive circulating tumor cell count, lymphocyte count and derived neutrophil-to- lymphocyte ratio for diagnosing lung cancer relapse.

The folate receptor-positive circulating tumor cell (FR+-CTC) count can be used to improve the diagnosis rate of lung cancer. The lymphocyte count (LC) and derived neutrophil-to-lymphocyte ratio (dNLR) are involved in inflammatory processes. Whether the FR+-CTC count combined with the dNLR or LC is helpful for diagnosing lung cancer recurrence is not clear. Sixty-eight patients who were initially diagnosed with lung cancer and received first-line treatment were included. The clinicopathological characteristics, routine blood examination results and CTC examination results of the patients were collected. The role of the complete blood count and FR+-CTC count in lung cancer treatment response and prognosis was analyzed. The FR+-CTC count after treatment was significantly correlated with the T stage (p=0.005). Multivariate analysis showed that the pathological type and FR+-CTC count were independent predictors of disease-or progression-free survival (DFS/PFS) in patients with lung cancer (p=0.010 and p=0.030, respectively). The FR+-CTC count, LC and dNLR predicted the recurrence of lung cancer (sensitivity and specificity of the FR+-CTC count, 69.2% and 71.4%; the LC, 50.0% and 88.5%; and the dNLR, 50.0% and 88.1%, respectively). The FR+-CTC count combined with the LC or dNLR improved the diagnostic rate of lung cancer recurrence (sensitivity and specificity of the FR+-CTC count plus the LC, 53.8% and 90.5%, and the FR+-CTC count plus the dNLR, 73.1% and 73.8%, respectively). When these three indicators were combined to predict lung cancer recurrence, the AUC value was 0.817. The FR+-CTC count combined with the dNLR and/or LC after treatment can improve the diagnostic rate of lung cancer recurrence. A higher FR+-CTC count predicts worse DFS/PFS in patients with lung cancer.

Sensitive detection of folate receptor-positive circulating tumor cells based on intracellular uptake of the PbS nanoparticle cluster-loaded phospholipid micelles decorated with folic acid in combination with E-DNA sensor

Developing methods for the circulating tumor cells (CTCs) detection is important for noninvasive cancer diagnosis. A sensitive method for homogeneous electrochemical detection of CTCs was developed based on the affinity of folic acid (FA) for folate receptor (FR), which is overexpressed on the CTC surface. The PbS nanoparticle cluster-loaded phospholipid micelles decorated with FA were prepared and used as a nanoprobe. The specific binding of FA to FR-positive CTCs leads to the uptake of the nanoprobes into the CTCs. Cellular imaging assay showed the excellent biocompatibility and selectivity of nanoprobes. After separation of intracellular nanoprobes and the residual free nanoprobes in the solution by centrifugation, nanoprobes in the cell were dissolved using acid. The amount of the target cells was quantified by the electrochemical detection of Pd2+ using the electrochemical DNA (E-DNA) sensor, which was fabricated based on the self-assembly of probe DNA on the flowerlike gold nanostructures modified the screen-printed carbon electrode (SPCE). Because of the large quantities of detectable Pd2+ contained in the nanoprobes, the signal amplification effect was achieved. The developed electrochemical assay allows the detection of ∼5 cells from 1 mL of sample. Studies with both healthy individuals and cancer patient blood samples demonstrate that the assay is sensitive and FR-positive CTCs specific.

Folate receptor-positive circulating tumor cells predict survival and recurrence patterns in patients undergoing resection for pancreatic cancer.

ObjectiveTo evaluate the prognostic impact of folate receptor (FR)-positive circulating tumor cells (FR+ CTCs) for patients with pancreatic cancer (PC).BackgroundRisk stratification before surgery for PC patients remains challenging as there are no reliable prognostic markers currently. FR+ CTCs, detected by ligand-targeted polymerase chain reaction (LT-PCR), have shown excellent diagnostic value for PC in our previous study and prognostic value in a variety of cancer types.MethodsPeripheral blood samples from 44 consecutive patients diagnosed with PC were analyzed for FR+ CTCs. 25 patients underwent tumor resection and were assigned to the surgical group. 19 patients failed to undergo radical resection because of local advance or distant metastasis and were assigned to the non-surgical group. The impact of CTCs on relapse and survival were explored.ResultsFor the prognostic stratification, the optimal cut-off value of CTCs analyzed by receiver operating characteristic (ROC) curve was 14.49 folate units (FU)/3 ml. High CTC levels (> 14.49 FU/3 ml) were detected in 52.0% (13/25) of the patients in the surgical group and 63.2% (12/19) in the non-surgical group. In the surgical group, median disease-free survival (DFS) for patients with high CTC levels versus low CTC levels (< 14.49 FU/3 ml) was 8.0 versus 26.0 months (P = 0.008). In multivariable analysis, CTCs were an independent risk factor for DFS (HR: 4.589, P = 0.012). Concerning the recurrence patterns, patients with high CTC levels showed a significantly frequent rate of distant and early recurrence (P = 0.017 and P = 0.011). CTC levels remained an independent predictor for both distant (OR: 8.375, P = 0.014) and early recurrence (OR: 8.412, P = 0.013) confirmed by multivariable logistic regression. However, CTCs did not predict survival in the non-surgical group (P = 0.220).ConclusionFR+ CTCs in resected PC patients could predict impaired survival and recurrence patterns after surgery. Preoperative CTC levels detected by LT-PCR may help guide treatment strategies and further studies in a larger cohort are warranted.

Folate receptor-positive circulating tumor cells in the preoperative diagnosis of indeterminate pulmonary nodules.

BackgroundThe use of FR + CTC to distinguish lung cancer from benign lung disease has been well studied. However, the effective method to differentiate precursor glandular lesions from benign/malignant pulmonary diseases is rare.Methods380 patients with indeterminate pulmonary nodules were prospectively recruited. Peripheral blood samples were collected from all participants before surgery for analyzing FR + CTC levels. The performance of FR + CTC to identify lung precursor lesions were analyzed by receiver operating characteristic (ROC) curve.ResultsFR + CTC can effectively differentiate precursor from benign pulmonary diseases in all included patients (cutoff: 9.22 FU/3 ml, AUC = 0.807, (p < 0.0001, sensitivity: 69.17%, specificity: 82.46%) and patients with single pulmonary lesion (cutoff: 9.03 FU/3 ml, AUC = 0.842, p = 0.0001, sensitivity: 75.20%, specificity: 83.00%). However, FR + CTC cannot differentiate precursor from benign pulmonary diseases in multiple lesions patients (p = 0.110). FR + CTC neither differentiate precursor from malignant pulmonary lesions in all included patients (p = 0.715), single nor multiple lesions patients (p = 0.867, p = 0.692, respectively). Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy (AOR, 95% CI: 3.104 (1.525, 6.316), 3.148 (1.722, 5.754), 2.098 (1.132, 3.888), respectively.ConclusionPreoperative FR + CTC can be identified in precursor glandular lesions and utilized to differentiate from benign pulmonary diseases. Total number of pulmonary nodules, MTD, location (lower vs upper) were independent risk factors for malignancy.

Wedge resection before lobectomy for patients with T1N0M0 non-small cell lung cancer: a propensity score matching analysis.

BackgroundWhether wedge resection of a tumor before lobectomy (Wed + Lob) can improve the prognosis of non-small cell lung cancer (NSCLC) has yet to be determined comprehensively. This study aimed to compare the effects of Wed + Lob with those of direct lobectomy (Lob) on survival and tumor cell dissemination in patients with T1N0M0 NSCLC.MethodsA cohort of 813 patients with T1N0M0 NSCLC who underwent lobectomy at a single center in China was investigated. After propensity score matching, the overall survival (OS) and disease-free survival (DFS) of patients were estimated using Kaplan-Meier plots. Associations between surgical strategies and patient survival were computed as hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Changes in folate receptor-positive circulating tumor cells (FR+ CTCs) after lobectomy were analyzed in another cohort from our hospital.ResultsA total of 401 Wed + Lob cases were matched with 255 Lob cases according to their propensity scores. Although no significant differences were found in OS, multivariate analysis showed that patients with T1N0M0 NSCLC in the Wed + Lob group had significantly improved DFS (HR =0.583; P=0.012) compared to those in the Lob group. After surgery, a decrease in FR+ CTCs was observed in 21 of 23 patients (91.3%) in the Wed + Lob group and in 16 of 23 patients (69.6%) in the Lob group [mean changes: 6.10 (±7.80) FU per 3 mL vs. 1.31 (±4.39) FU per 3 mL; P=0.014].ConclusionsWed + Lob may improve DFS and reduce tumor cell dissemination in patients with T1N0M0 NSCLC.

Preoperative Folate Receptor-Positive Circulating Tumor Cells Are Associated With Occult Peritoneal Metastasis and Early Recurrence in Gastric Cancer Patients: A Prospective Cohort Study.

BackgroundThe aim of this study is to explore the clinical feasibility of detecting folate receptor-positive circulating tumor cells (FR+ CTCs) for predicting peritoneal metastasis and short-term outcome in gastric cancer patients.MethodsThis is a prospective, single-center, observational study. We applied ligand-targeted enzyme-linked polymerization method to detect preoperative FR+ CTC levels in peripheral blood. We evaluated the diagnostic value of FR+ CTCs and other biomarkers in predicting peritoneal metastasis. Prognostic factors for recurrence-free survival (RFS) were investigated in univariate and multivariate analyses.ResultsA total of 132 patients with gastric cancer and 9 patients with benign disease were recruited. Gastric cancer patients had a significantly higher CTC level compared to that of patients with benign disease (p < 0.01). Combined model including CTC level and other biomarkers presented high sensitivity (100%) and moderate specificity (59.3%) in predicting peritoneal metastasis. Univariate analysis revealed that decreased serum prealbumin, decreased peripheral lymphocyte count, FR+ CTCs, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and lymph node metastasis were significantly associated with shorter RFS. FR+ CTC level [≥12.6 folate units (FU)/3 ml, hazard ratio (HR) = 6.957, p = 0.005] and CA19-9 (>34 ng/ml, HR = 3.855, p = 0.037) were independent prognostic factors in multivariate analysis.ConclusionsOur findings for the first time suggested the diagnostic value of preoperative CTC levels in predicting peritoneal metastasis in gastric cancer. Moreover, the FR+ CTC level could be a novel and promising prognostic factor for the recurrence of gastric cancer in patients who underwent surgery.Clinical Trial RegistrationChinese Clinic Trial Registry, identifier ChiCTR2100050514.

The role of folate receptor-positive circulating tumor cell analysis in the diagnosis of colorectal cancer: a retrospective cohort study

To explore the application value of folate receptor-positive circulating tumor cell analysis (FR+-CTC analysis) in the diagnosis of colorectal cancer (CRC). Clinical data of CRC patients and healthy subjects admitted to our hospital from January 2019 to October 2019 were retrospectively collected. CTC result and serological and pathological outcomes of the study patients were collected and analyzed. Receiver operating characteristic curve (ROC curve) was drawn. The CTC levels of cancer patients (9.34 ± 3.53 FU/3ml) were significantly higher than those of healthy subjects (7.00 ± 2.33 FU/3ml). CTC levels could be related to cancer stage and metastasis in patients. ROC curves were drawn and the area under the ROC curve (AUC) was 0.702. The cutoff value was determined to be 8.87 FU/3ml. At this cutoff value, the sensitivity and specificity of FR+-CTC analysis in the diagnosis of colorectal cancer were 61.8% and 82.6%, respectively. The diagnostic efficiency of FR+-CTCs in advanced CRC was significantly higher than that in the early stage. And the cutoff value of early and advanced stage CRC was determined to be 9.66 FU/3ml. FR+-CTC analysis has high potential in recurrence diagnosis and decision of adjuvant chemotherapy for CRC.

The combination of folate receptor-positive circulating tumor cells and serum tumor markers suggests a histological diagnosis of lung cancer.

BackgroundFolate-receptor alpha (FRα) is overexpressed in lung carcinoma. The FR-positive circulating tumor cell (FR+ CTC) has been established to be a non-invasive biomarker for lung cancer diagnosis. In this study, we sought to examine the value of FR+ CTC in the histological diagnosis of suspicious space-occupying pulmonary lesions.MethodsA total of 538 patients with suspicious space-occupying pulmonary lesions were enrolled in this study. FR+ CTCs were detected before treatment initiation using negative enrichment and ligand-targeted polymerase chain reaction assays. The enrolled patients concurrently received serum biomarker tests.ResultsA total of 282 lung cancer patients [163 with adenocarcinoma (ADC), 71 with squamous cell carcinoma (SCC), and 48 with small cell lung cancer (SCLC)], and 256 patients with benign disease who concurrently received FR+ CTC and serum biomarker tests were randomly assigned to a training set and a validation set. The FR+ CTC levels of patients with lung cancer were significantly higher than those of patients with benign disease (P<0.001). Compared to serum tumor biomarkers alone, the model combining FR+ CTC and serum biomarkers had the highest area under the receiver operating characteristic curve in the diagnosis of NSCLC, ADC, SCC, and SCLC.ConclusionsDiagnostic models that include both FR+ CTC and serum biomarkers could increase the efficiency of distinguishing between different histological types of lung cancer and benign space-occupying pulmonary diseases.

Detection of folate receptor-positive circulating tumor cells as a biomarker for diagnosis, prognostication, and therapeutic monitoring in breast cancer.

ObjectivesThis study is to explore the clinical significance of folate receptor‐positive circulating tumor cells (FR+CTC) in the early diagnosis and disease progress in patients with breast cancer.MethodsFolate receptor‐positive circulating tumor cells was enriched from peripheral blood of the patients with immunomagnetic separation method and quantitated by folate receptor on the CTC with the ligand‐targeted PCR.ResultsThe levels of FR+CTC were significantly higher in breast cancer patients compared with healthy controls. Detective rate of FR+CTC was decreased in 19 of 27 patients underwent the surgery in 2 weeks post‐operation compared with pre‐operation; statistical analysis showed the difference was significant. We also found that the combination of FR+CTC, CEA, CA125, and CA153 can significantly improve the diagnostic efficiency for breast cancer.ConclusionsThis study showed the detective rate of FR+CTC is significantly increased in the patients with breast cancer, and the detective level is associated with disease progress.

Folate-Receptor Positive Circulating Tumor Cell Is a Potential Diagnostic Marker of Prostate Cancer.

Folate-receptor positive circulating tumor cells (FR+CTCs) shows an important role in the diagnosis and dynamic monitoring for many solid tumors; however, the application of FR+CTCs in prostate cancer remains unclear. We explored the potential application of FR+CTCs in this retrospective study. The levels of FR+CTCs were detected in 30 prostate cancer patients and 7 bladder cancer patients in Peking University Cancer Hospital from August 2017 to August 2021. Clinical and pathology data were collected. One-way ANOVA was used to compare the difference in FR+CTCs levels in patients with prostate cancer, bladder cancer, and benign disease. The area under the receiver operating curve (AUROC) was used to compare the accuracy of FR+CTCs and tPSA in the diagnosis of prostate cancer. We found that levels of FR+CTCs were significantly higher in cancer patients (both prostate and bladder cancer) than in patients with benign urinary disease (p < 0.001). Besides, FR+CTCs level was consistently high in the prostate cancer patients with different tPSA levels (p < 0.001), and it was significantly higher in the patients with f/tPSA levels <0.16 than in those patients with f/tPSA levels >0.16 (12.20 ± 1.31 vs. 8.73 ± 0.92 FU/3 ml, p = 0.043). The diagnosis efficiency of FR+CTCs is better than the tPSA in prostate cancer patients with tPSA <10 ng/ml (0.871 vs. 0.857). In the prostate cancer patients with tPSA <10 ng/ml and f/tPSA <0.16, a combination of FR+CTCs and tPSA (AUROC, 0.934) further increased the diagnosis efficiency of each of these biomarkers alone (FR+CTCs, 0.912; tPSA, 0.857). Therefore, FR+CTCs could serve as an early diagnosis marker in the prostate cancer patients with uncertain tPSA levels.

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

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.

A preliminary study of the clinical significance of folate receptor-positive circulating tumor cell in the management of hepatobiliary-pancreatic cancers.

BackgroundHepatobiliary-pancreatic cancers (HBPs) are highly lethal, partly because of their usually late diagnosis. This multi-center, observational study aimed to explore the clinical significance of folate receptor-positive circulating tumor cell (FR+CTC) as a liquid biopsy approach in the differential diagnosis and management of HBPs.MethodsWe recruited 119 patients suspicious for HBPs and 60 cancer-free healthy individuals in the present study. Patients without definitive pathological assessment or without pre-operative FR+CTC analysis were excluded. FR+CTC was tested prior to surgery or tissue biopsy using the CytoploRare® Detection Kit. Serum biomarkers, including CA 125, CA 19-9, and CEA, were tested in selected patients. Post-operative FR+CTC analysis was also performed in a subset of the patients receiving surgical resection.ResultsWith 8.65 FU/3 mL as the cut-off value, the sensitivity and specificity of FR+CTC in differential diagnosis were 98.1% and 79.1%, respectively. The detection rate of FR+CTC was superior to conventional serum biomarkers (CA 19-9 > CA 125 > CEA). For the 16patients with matched post-operative FR+CTC analysis, FR+CTC levels significantly reduced after surgery (P=0.0084).ConclusionsOur results demonstrated that FR+CTC analysis could be an efficacious non-invasive biomarker in differential diagnosis and surveillance of HBPs, though further investigation with a larger sample size is required.