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

Abstract

Background: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4⁺CTC) 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 OCT4⁺CTC 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, OCT4^-CTC, and OCT4⁺CTC groups. Patients were followed up for a median of 10.4 months.

Results: The percentages of patients in none CTC, OCT4^-CTC, and OCT4⁺CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4⁺CTC group, followed by none CTC group, and lowest in OCT4^-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4⁺CTC group, moderate in OCT4^-CTC 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 OCT4⁺CTC group than in none CTC & OCT4^-CTC group. Moreover, OCT4⁺CTC (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: OCT4⁺CTC 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.

Keywords: Cholangiocarcinoma; Circulating tumor cell; Immune checkpoint inhibitors; Octamer-binding transcription factor 4; Prognosis.

Fig. 1

The proportions of advanced CCA patients with none CTC, OCT4⁻CTC, and OCT4⁺CTC

Fig. 2

PFS in the none CTC, OCT4⁻CTC, and OCT4⁺CTC groups. Comparison of PFS among none CTC, OCT4⁻CTC, and OCT4⁺CTC groups (A); comparison of PFS between none CTC & OCT4⁻CTC and OCT4⁺CTC groups (B)

Fig. 3

OS in the none CTC, OCT4⁻CTC, and OCT4⁺CTC groups. Comparison of OS among none CTC, OCT4⁻CTC, and OCT4⁺CTC groups (A); comparison of OS between none CTC & OCT4⁻CTC and OCT4⁺CTC groups (B)

Fig. 4

Univariate and multivariate Cox regression analyses of PFS in advanced CCA patients. Univariate Cox regression analysis was used to predict PFS (A); multivariate Cox regression analysis was used to identify independent predictors of PFS (B) in advanced CCA patients

Fig. 5

Univariate and multivariate Cox regression analyses of OS in advanced CCA patients. Univariate Cox regression analysis was used to predict OS (A); multivariate Cox regression analysis was used to identify independent predictors of OS (B) in advanced CCA patients