PMID- 34103974 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220423 IS - 1178-7074 (Print) IS - 1178-7074 (Electronic) IS - 1178-7074 (Linking) VI - 14 DP - 2021 TI - High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection. PG - 2191-2204 LID - 10.2147/IJGM.S306339 [doi] AB - BACKGROUND: 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. CI - (c) 2021 Titapun et al. FAU - Titapun, Attapol AU - Titapun A AUID- ORCID: 0000-0002-2228-752X AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. FAU - Luvira, Vor AU - Luvira V AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. FAU - Srisuk, Tharatip AU - Srisuk T AUID- ORCID: 0000-0001-7850-2500 AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. FAU - Jareanrat, Apiwat AU - Jareanrat A AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. FAU - Thanasukarn, Vasin AU - Thanasukarn V AUID- ORCID: 0000-0002-7976-1915 AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. FAU - Thanee, Malinee AU - Thanee M AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Sa-Ngiamwibool, Prakasit AU - Sa-Ngiamwibool P AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Padthaisong, Sureerat AU - Padthaisong S AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Duangkumpha, Kassaporn AU - Duangkumpha K AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Suksawat, Manida AU - Suksawat M AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Loilome, Watcharin AU - Loilome W AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Sithithaworn, Paiboon AU - Sithithaworn P AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. FAU - Techasen, Anchalee AU - Techasen A AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. FAU - Thinkhamrop, Bandit AU - Thinkhamrop B AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. AD - Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand. FAU - Dzienny, Alexa AU - Dzienny A AD - School of Medicine and Health Sciences, George Washington University, Washington, DC, USA. FAU - Caglayan, Ayse AU - Caglayan A AD - Faculty of Medicine, Imperial College London, London, UK. FAU - Park, David AU - Park D AUID- ORCID: 0000-0001-6898-3662 AD - Faculty of Medicine, Imperial College London, London, UK. FAU - Mahmud, Simran AU - Mahmud S AUID- ORCID: 0000-0003-4125-7489 AD - Faculty of Medicine, Imperial College London, London, UK. FAU - Khuntikeo, Narong AU - Khuntikeo N AUID- ORCID: 0000-0001-9305-0688 AD - Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Cholangiocarcinoma Research Institute (CARI), Khon Kaen University, Khon Kaen, Thailand. LA - eng PT - Journal Article DEP - 20210601 PL - New Zealand TA - Int J Gen Med JT - International journal of general medicine JID - 101515487 PMC - PMC8179826 OTO - NOTNLM OT - CCA OT - CD44s OT - CD44v8-10 OT - OV IgG antibody OT - OV-associated CCA OT - survival COIS- The authors report no conflicts of interest in this work. EDAT- 2021/06/10 06:00 MHDA- 2021/06/10 06:01 PMCR- 2021/06/01 CRDT- 2021/06/09 06:41 PHST- 2021/02/14 00:00 [received] PHST- 2021/04/29 00:00 [accepted] PHST- 2021/06/09 06:41 [entrez] PHST- 2021/06/10 06:00 [pubmed] PHST- 2021/06/10 06:01 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - 306339 [pii] AID - 10.2147/IJGM.S306339 [doi] PST - epublish SO - Int J Gen Med. 2021 Jun 1;14:2191-2204. doi: 10.2147/IJGM.S306339. eCollection 2021.