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TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications.

ABSTRACT: TLR4 and pSTAT3 are key players in cancer inflammation and immune evasion; however, their role in the peripheral blood (PB) is largely unexplored. Herein we evaluated their expression in the circulating tumor cells (CTCs) and peripheral-blood mononuclear cells (PBMCs) of patients with early (n = 99) and metastatic (n = 100) breast cancer (BC). PB samples obtained prior to adjuvant and first-line therapy, were immunofluorescently stained for Cytokeratins/TLR4/pSTAT3/DAPI and analyzed via Ariol microscopy. TLR4+ CTCs were detected in 50% and 68% of early and metastatic CTC-positive patients, respectively, and pSTAT3+ CTCs in 83% and 68%, respectively. In metastatic patients, CTC detection was associated with a high risk of death (HR: 1.764, p = 0.038), while TLR4+ CTCs correlated with a high risk of disease progression (HR: 1.964, p = 0.030). Regarding PBMCs, TLR4 expression prevailed in metastatic disease (p = 0.029), while pSTAT3 expression was more frequent in early disease (p = 0.014). In early BC, TLR4 expression on PBMCs independently predicted for high risk of relapse (HR: 3.549; p = 0.009), whereas in metastatic BC, TLR4+/pSTAT3- PBMCs independently predicted for high risk of death (HR: 2.925; p = 0.012). These results suggest that TLR4/pSTAT3 signaling on tumor- and immune-cell compartments in the PB could play a role in BC progression, and may hold independent prognostic implications for BC patients.

SUBMITTER: Papadaki MA

PROVIDER: S-EPMC8869985 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications.

Papadaki Maria A MA Monastirioti Alexia A Apostolopoulou Christina A CA Aggouraki Despoina D Papadaki Chara C Michaelidou Kleita K Vassilakopoulou Maria M Alexakou Katerina K Mavroudis Dimitrios D Agelaki Sofia S

Cancers 20220218 4

TLR4 and pSTAT3 are key players in cancer inflammation and immune evasion; however, their role in the peripheral blood (PB) is largely unexplored. Herein we evaluated their expression in the circulating tumor cells (CTCs) and peripheral-blood mononuclear cells (PBMCs) of patients with early (<i>n</i> = 99) and metastatic (<i>n</i> = 100) breast cancer (BC). PB samples obtained prior to adjuvant and first-line therapy, were immunofluorescently stained for Cytokeratins/TLR4/pSTAT3/DAPI and analyze ...[more]

PMID: 35205801

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Project description:BackgroundCirculating tumor cells (CTCs) are important biological indicators of the lung cancer prognosis, and CTC counting and typing may provide helpful biological information for the diagnosis and treatment of lung cancer.MethodsThe CTC count in blood before and after radiotherapy was detected by the CanPatrol™ CTC analysis system, and the CTC subtypes and the expression of hTERT before and after radiotherapy were detected by multiple in situ hybridization. The CTC count was calculated as the number of cells per 5 mL of blood.ResultsThe CTC positivity rate in patients with tumors before radiotherapy was 98.44%. Epithelial-mesenchymal CTCs (EMCTCs) were more common in patients with lung adenocarcinoma and squamous carcinoma than in patients with small cell lung cancer (P = 0.027). The total CTCs (TCTCs), EMCTCs, and mesenchymal CTCs (MCTCs) counts were significantly higher in patients with TNM stage III and IV tumors (P < 0.001, P = 0.005, and P < 0.001, respectively). The TCTCs and MCTCs counts were significantly higher in patients with an ECOG score of > 1 (P = 0.022 and P = 0.024, respectively). The TCTCs and EMCTCs counts before and after radiotherapy affected the overall response rate (ORR) (P < 0.05). TCTCs and ECTCs with positive hTERT expression were associated with the ORR of radiotherapy (P = 0.002 and P = 0.038, respectively), as were TCTCs with high hTERT expression (P = 0.012). ECOG score (P = 0.006) and post-radiation TCTCs count (P = 0.011) were independent factors for progression-free survival (PFS) and TNM stage (P = 0.054) and pre-radiation EMCTCs count (P = 0.009) were independent factors of overall survival (OS).ConclusionThis study showed a high rate of positive CTC detection in patients with lung cancer, and the number, subtype, and hTERT-positive expression of CTCs were closely related to patients' ORR, PFS, and OS with radiotherapy. EMCTCs, hTERT-positive expression of CTCs are expected to be important biological indicators for predicting radiotherapy efficacy and the prognosis in patients with lung cancer. These results may be useful in improving disease stratification for future clinical trials and may help in clinical decision-making.

Dataset Information

TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications.

Publications

TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications.

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