Predictive Value of Folate Receptor‐Positive Circulating Tumor Cells for the Preoperative Diagnosis of Lymph Node Metastasis in Patients with Lung Adenocarcinoma

Zhao, Li; Xu, Ke; Xu, Lekai; Dai, Jie; Jin, Kaiqi; Zhu, Yuming; Yang, Yang; Jiang, Gening

doi:10.1002/smtd.202100152

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…The main mode of PM is peritoneal dissemination, while CTCs mainly contribute to the hematogenous metastasis. A recent study showed the value of FR+ CTC level in predicting lymph node metastasis in patients with lung adenocarcinoma ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…3 Moreover, the LN status of NSCLC is a pivotal factor in determining the accurate stage of patients and the optimal therapeutic modality. 4 Although the crucial role of LN metastasis has been well established in NSCLC, the limited understanding of the associated regulatory mechanism greatly impedes the development of effective targeted therapies against LN metastatic NSCLC.…”

Section: Introductionmentioning

confidence: 99%

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

Diao,

Guo,

Zheng

et al. 2023

Sig Transduct Target Ther

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Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

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New insights into the correlations between circulating tumor cells and target organ metastasis

Zhan,

Liu,

Situ

et al. 2023

Sig Transduct Target Ther

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Organ-specific metastasis is the primary cause of cancer patient death. The distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in their microenvironment. During an intermediate stage of metastasis, circulating tumor cells (CTCs) are released into the bloodstream from primary and metastatic tumors. CTCs harboring aggressive or metastatic features can extravasate to remote sites for continuous colonizing growth, leading to further lesions. In the past decade, numerous studies demonstrated that CTCs exhibited huge clinical value including predicting distant metastasis, assessing prognosis and monitoring treatment response et al. Furthermore, increasingly numerous experiments are dedicated to identifying the key molecules on or inside CTCs and exploring how they mediate CTC-related organ-specific metastasis. Based on the above molecules, more and more inhibitors are being developed to target CTCs and being utilized to completely clean CTCs, which should provide promising prospects to administer advanced tumor. Recently, the application of various nanomaterials and microfluidic technologies in CTCs enrichment technology has assisted to improve our deep insights into the phenotypic characteristics and biological functions of CTCs as a potential therapy target, which may pave the way for us to make practical clinical strategies. In the present review, we mainly focus on the role of CTCs being involved in targeted organ metastasis, especially the latest molecular mechanism research and clinical intervention strategies related to CTCs.

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Predictive Value of Folate Receptor‐Positive Circulating Tumor Cells for the Preoperative Diagnosis of Lymph Node Metastasis in Patients with Lung Adenocarcinoma

Cited by 4 publications

References 29 publications

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

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

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

New insights into the correlations between circulating tumor cells and target organ metastasis

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