Octamer-binding Transcription Factor 4-positive Circulating Tumor Cell Predicts Worse Treatment Response and Survival in Advanced Cholangiocarcinoma Patients Who Receive Immune Checkpoint Inhibitors Treatment

Overview

Journal World J Surg Oncol

Publisher Biomed Central

Specialties General Surgery
Oncology

Date 2024 Apr 25

PMID 38664770

Authors

Fei Pei

Zhen Tao

Qi Lu

Tao Fang

Shasha Peng

Affiliations

Soon will be listed here.

Abstract

Background: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment.

Methods: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4CTC, and OCT4CTC groups. Patients were followed up for a median of 10.4 months.

Results: The percentages of patients in none CTC, OCT4CTC, and OCT4CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4CTC group, followed by none CTC group, and lowest in OCT4CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4CTC group, moderate in OCT4CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4CTC group than in none CTC & OCT4CTC group. Moreover, OCT4CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients.

Conclusion: OCT4CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.

Citing Articles

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PMID: 39099760 PMC: 11296367. DOI: 10.2147/CMAR.S474348.

References

Banales J, Cardinale V, Carpino G, Marzioni M, Andersen J, Invernizzi P . Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016; 13(5):261-80. DOI: 10.1038/nrgastro.2016.51. View

Rizzo A, Frega G, Ricci A, Palloni A, Abbati F, De Lorenzo S . Anti-EGFR Monoclonal Antibodies in Advanced Biliary Tract Cancer: A Systematic Review and Meta-analysis. In Vivo. 2020; 34(2):479-488. PMC: 7157865. DOI: 10.21873/invivo.11798. View

Zhang Q, Rong Y, Yi K, Huang L, Chen M, Wang F . Circulating tumor cells in hepatocellular carcinoma: single-cell based analysis, preclinical models, and clinical applications. Theranostics. 2020; 10(26):12060-12071. PMC: 7667686. DOI: 10.7150/thno.48918. View

Wang Y, Herlyn M . The emerging roles of Oct4 in tumor-initiating cells. Am J Physiol Cell Physiol. 2015; 309(11):C709-18. PMC: 4725440. DOI: 10.1152/ajpcell.00212.2015. View

Liu T, Sun B, Zhao X, Li Y, Gu Q, Dong X . OCT4 expression and vasculogenic mimicry formation positively correlate with poor prognosis in human breast cancer. Int J Mol Sci. 2014; 15(11):19634-49. PMC: 4264130. DOI: 10.3390/ijms151119634. View

Shi X, Liu Y, Cheng S, Hu H, Zhang J, Wei M . Cancer Stemness Associated With Prognosis and the Efficacy of Immunotherapy in Adrenocortical Carcinoma. Front Oncol. 2021; 11:651622. PMC: 8334864. DOI: 10.3389/fonc.2021.651622. View

Liu J, Ren W, Shu J . Multimodal molecular imaging evaluation for early diagnosis and prognosis of cholangiocarcinoma. Insights Imaging. 2022; 13(1):10. PMC: 8776965. DOI: 10.1186/s13244-021-01147-7. View

Rodrigues P, Vogel A, Arrese M, Balderramo D, Valle J, Banales J . Next-Generation Biomarkers for Cholangiocarcinoma. Cancers (Basel). 2021; 13(13). PMC: 8269024. DOI: 10.3390/cancers13133222. View

Maccalli C, Rasul K, Elawad M, Ferrone S . The role of cancer stem cells in the modulation of anti-tumor immune responses. Semin Cancer Biol. 2018; 53:189-200. PMC: 8668198. DOI: 10.1016/j.semcancer.2018.09.006. View

10.

Wang J, Ilyas S . Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy. Expert Opin Investig Drugs. 2020; 30(4):429-438. PMC: 8096665. DOI: 10.1080/13543784.2021.1865308. View

11.

Elvevi A, Laffusa A, Gallo C, Invernizzi P, Massironi S . Any Role for Microbiota in Cholangiocarcinoma? A Comprehensive Review. Cells. 2023; 12(3). PMC: 9913249. DOI: 10.3390/cells12030370. View

12.

Brindley P, Bachini M, Ilyas S, Khan S, Loukas A, Sirica A . Cholangiocarcinoma. Nat Rev Dis Primers. 2021; 7(1):65. PMC: 9246479. DOI: 10.1038/s41572-021-00300-2. View

13.

Wu S, Liu S, Liu Z, Huang J, Pu X, Li J . Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One. 2015; 10(4):e0123976. PMC: 4409386. DOI: 10.1371/journal.pone.0123976. View

14.

Spranger S, Bao R, Gajewski T . Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015; 523(7559):231-5. DOI: 10.1038/nature14404. View

15.

Massironi S, Pilla L, Elvevi A, Longarini R, Rossi R, Bidoli P . New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma. Cells. 2020; 9(3). PMC: 7140695. DOI: 10.3390/cells9030688. View

16.

Li M, Zhang B, Zhang Z, Liu X, Qi X, Zhao J . Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer. Biomed Res Int. 2014; 2014:981261. PMC: 4054962. DOI: 10.1155/2014/981261. View

17.

Chen P, Hsu W, Han J, Xia Y, DePinho R . Cancer Stemness Meets Immunity: From Mechanism to Therapy. Cell Rep. 2021; 34(1):108597. PMC: 7839836. DOI: 10.1016/j.celrep.2020.108597. View

18.

Santoni M, Rizzo A, Mollica V, Matrana M, Rosellini M, Faloppi L . The impact of gender on The efficacy of immune checkpoint inhibitors in cancer patients: The MOUSEION-01 study. Crit Rev Oncol Hematol. 2022; 170:103596. DOI: 10.1016/j.critrevonc.2022.103596. View

19.

Katoh M, Katoh M . WNT signaling and cancer stemness. Essays Biochem. 2022; 66(4):319-331. PMC: 9484141. DOI: 10.1042/EBC20220016. View

20.

Lu C, Shieh G, Wang C, Su B, Su Y, Chen Y . Chemotherapeutics-induced Oct4 expression contributes to drug resistance and tumor recurrence in bladder cancer. Oncotarget. 2016; 8(19):30844-30858. PMC: 5458172. DOI: 10.18632/oncotarget.9602. View