International Journal of General Medicine (Jun 2021)

High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection

  • Titapun A,
  • Luvira V,
  • Srisuk T,
  • Jareanrat A,
  • Thanasukarn V,
  • Thanee M,
  • Sa-Ngiamwibool P,
  • Padthaisong S,
  • Duangkumpha K,
  • Suksawat M,
  • Loilome W,
  • Sithithaworn P,
  • Techasen A,
  • Thinkhamrop B,
  • Dzienny A,
  • Caglayan A,
  • Park D,
  • Mahmud S,
  • Khuntikeo N

Journal volume & issue
Vol. Volume 14
pp. 2191 – 2204

Abstract

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Attapol Titapun,1,2 Vor Luvira,1,2 Tharatip Srisuk,1,2 Apiwat Jareanrat,1,2 Vasin Thanasukarn,1,2 Malinee Thanee,2,3 Prakasit Sa-Ngiamwibool,2,3 Sureerat Padthaisong,2,4 Kassaporn Duangkumpha,2,4 Manida Suksawat,2,4 Watcharin Loilome,2,4 Paiboon Sithithaworn,2,5 Anchalee Techasen,2,6 Bandit Thinkhamrop,2,7 Alexa Dzienny,8 Ayse Caglayan,9 David Park,9 Simran Mahmud,9 Narong Khuntikeo1,2 1Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand; 3Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 4Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 5Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 6Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand; 7Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand; 8School of Medicine and Health Sciences, George Washington University, Washington, DC, USA; 9Faculty of Medicine, Imperial College London, London, UKCorrespondence: Attapol TitapunDepartment of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandTel +66-43-363252Email [email protected]: Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA) has a high immune response with chronic inflammation and oxidative stress. CD44 and Nestin, two cancer stem cell (CSC) markers, play major roles in cancer cell survival. Effects of immune response and expression CSC markers on survival of patients with CCA remain unclear.Objective: To investigate the effects of level of OV IgG together with CSC marker expression and also the combination of these markers on survival of CCA patients after curative resection.Methods: All serum specimens from CCA patients who underwent curative surgery from 2005 to 2015 were examined for IgG for OV antigen by ELISA. Tissue specimens were studied for CD44 and Nestin expression. Survival analysis by Cox proportional hazard model was used for estimating hazard ratio (HR) with a 95% confidence interval (CI).Results: In this study, 122 (69.3%) of 176 were positive for OV IgG, and 35 (19.9%) were considered to have high-positive OV IgG. CD44s positive expression was found in 54 (40%), CD44v6 high expression in 96 (69.6%), CD44v8-10 high expression in 87 (63.5%) and Nestin high expression in 21 (16.1%). Multivariate survival analysis found that high-positive OV IgG and late stage tumor were independent prognostic factors with the adjusted HR of 2.24 (95% CI 1.27– 3.93) and 2.78 (95% CI 1.46– 5.29), respectively. Subgroup analysis in early and late stage CCA showed that a combined positive OV IgG and CD44s expression with the high expression of CD44v8-10 had the significantly poorest prognosis with HR of 3.75 (95% CI 1.61– 8.72) and HR of 1.76 (95% CI 1.02– 3.03), respectively.Conclusion: A high level of OV IgG as well as a high level of CSC markers resulted in an aggressive CCA. OV IgG level together with CSC markers can be used as the prognostic markers for CCA patients’ survival. The study of the CD44 pathway is promising for adjuvant treatment.Keywords: CCA, OV‐associated CCA, survival, OV IgG antibody, CD44s, CD44v8-10

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