Serum Levels of Cytokine-Induced Apoptosis Inhibitor 1 (CIAPIN1) as a Potential Prognostic Biomarker of Cholangiocarcinoma

Truong, Son Dinh An; Tummanatsakun, Doungdean; Proungvitaya, Tanakorn; Limpaiboon, Temduang; Wongwattanakul, Molin; Chua‐On, Daraporn; Roytrakul, Sittiruk; Proungvitaya, Siriporn

doi:10.3390/diagnostics11061054

Cited by 4 publications

(9 citation statements)

References 33 publications

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“…The Western blot analysis was performed for the detection of CIAPIN1 protein in CCA cell lysate as described previously [7]. Briefly, cells were lysed with lysis buffer (Cat#9806, RIPA, Cell Signaling Technologies, Danvers, MA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…In the previous study of our group, Chua-On et al identified a total of 281 mitochondrial proteins, 105 of which were overexpressed in the cancerous tissue of CCA compared with adjacent non-cancerous tissues [6]. Among them, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) was identified as a potential prognostic biomarker for CCA [7]. In particular, the serum CIAPIN1 level was significantly higher in CCA patients with lymph node metastasis than those without metastasis [7].…”

Section: Introductionmentioning

confidence: 96%

“…Among them, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) was identified as a potential prognostic biomarker for CCA [7]. In particular, the serum CIAPIN1 level was significantly higher in CCA patients with lymph node metastasis than those without metastasis [7].…”

Section: Introductionmentioning

confidence: 99%

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Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis

Truong

Wongwattanakul

Proungvitaya

et al. 2022

JCM

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Cholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated further its expression in CCA tissues, biological functions, and related signaling pathways in CCA cells. First, we examined CIAPIN1 expression in CCA tissues of 39 CCA patients using immunohistochemistry (IHC). Then, CIAPIN1-related proteins expressed in CCA cells were identified using RNA interference (siRNA) and liquid chromatography–mass spectrometry (LC–MS/MS). To predict the functions and signaling pathways of CIAPIN1 in CCA cells, the identified proteins were analyzed using bioinformatics tools. Then, to validate the biological functions of CIAPIN1 in the CCA cell line, transwell migration/invasion assays were used. CIAPIN1 was overexpressed in CCA tissues compared with adjacent noncancerous tissues. Its overexpression was correlated with lymph node metastasis. Bioinformatic analyses predicted that CIAPIN1 is connected to the TGF-β/SMADs signaling pathway via nitric oxide synthase 1 (NOS1) and is involved in the metastasis of CCA cells. In fact, cell migration and invasion activities of the KKU-100 CCA cell line were significantly suppressed by CIAPIN1 gene silencing. Our results unravel its novel function and potential signaling pathway in metastasis of CCA cells. CIAPIN1 can be a poor prognostic factor and can be a promising target molecule for CCA chemotherapy.

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Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis

Truong

Wongwattanakul

Proungvitaya

et al. 2022

JCM

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“…The serum has also emerged as a biospecimen towards prognostic biomarkers exploration (Table 3 ). As such, high levels of tissue Krebs von den Lungen 6 (KL-6 mucin)[ 63 ], cadherin-17 (CDH17)[ 64 ], kallikrein-11[ 65 ], uPAR[ 59 ] and high levels of serum cytokine-induced apoptosis inhibitor 1 (CIAPIN1)[ 66 ], MUC5AC[ 55 ], OPN[ 50 ], S100A6[ 67 ] and uPAR[ 59 , 68 ] were found adverse prognostic factors for CCA patient’s survival. Subjected to meta-analysis, high levels of tissue PD-L1[ 17 ] and tissue protein S100P[ 69 ] were also proposed as potential prognostic markers of CCA.…”

Section: Proteinsmentioning

confidence: 99%

Novel approaches in search for biomarkers of cholangiocarcinoma

Mocan¹,

Ilieș²,

Melincovici³

et al. 2022

WJG

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Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

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“…For instance, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX-1) was a secreted protein which identified as a potential serum marker for diagnosis and prognosis of CCA ( 16 ). Moreover, other members of our group identified coiled-coil domain containing 25 (CCDC25), apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) and cytokine-induced apoptosis inhibitor 1 (CIAPIN1) as potential secreted protein biomarkers in CCA ( 17 – 19 ). In this study, we performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of CCA patients' sera who were pathologically diagnosed with both vascular invasion and lymph node metastasis with ≤ 1 year survival time and >1 year survival time for searching a potential prognostic biomarker of CCA.…”

Section: Introductionmentioning

confidence: 98%

Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients

Aung

Ciin

Silsirivanit

et al. 2022

Front. Public Health

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Cholangiocarcinoma (CCA) is a tumor arising from cholangiocytes lining the bile ducts. Vascular invasion and lymph node metastasis are important prognostic factors for disease staging as well as clinical therapeutic decisions for CCA patients. In the present study, we applied CCA sera proteomic analysis to identify a potential biomarker for prognosis of CCA patients. Then, using bioinformatics tools, we identified angiopoietin-like protein 4 (ANGPTL4) which expressed highest signal intensity among candidate proteins in proteomic analysis of CCA sera. Expression of ANGPTL4 in CCA tissues was determined using immunohistochemistry. The results showed that ANGPTL4 was stained at higher level in CCA cells when compared with normal cholangiocytes. The high expression of ANGPTL4 was associated with lymph node metastasis and advanced tumor stage (p = 0.013 and p = 0.031, respectively). Furthermore, serum ANGPTL4 levels in CCA and healthy control (HC) were analyzed using a dot blot assay. And it was found that ANGPTL4 level was significantly higher in CCA than HC group (p < 0.0001). ROC curve analysis revealed that serum ANGPTL4 level was effectively distinguished CCA from healthy patients (cutoff = 0.2697 arbitrary unit (AU), 80.0% sensitivity, 72.7% specificity, AUC = 0.825, p < 0.0001). Serum ANGPTL4 level was associated with vascular invasion and lymph node metastasis (p = 0.0004 and p = 0.006), so that it differentiated CCA with vascular invasion from CCA without vascular invasion (cutoff = 0.5526 AU, 64.9% sensitivity, 92.9% specificity, AUC = 0.751, p = 0.006) and it corresponded to CCA with/without lymph node metastasis (cutoff = 0.5399 AU, 71.4% sensitivity, 70.8% specificity, AUC = 0.691, p = 0.01) by ROC analysis. Serum ANGPTL4 levels showed superior predictive efficiency compared with CA 19-9 and CEA for vascular invasion and lymph node metastasis. In addition, serum ANGPTL4 level was an independent predictive indicator by multivariate regression analysis. In conclusion, serum ANGPTL4 could be a novel prognostic biomarker for prediction of vascular invasion and lymph node metastasis of CCA patients.

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Serum Levels of Cytokine-Induced Apoptosis Inhibitor 1 (CIAPIN1) as a Potential Prognostic Biomarker of Cholangiocarcinoma

Cited by 4 publications

References 33 publications

Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis

Prediction of CIAPIN1 (Cytokine-Induced Apoptosis Inhibitor 1) Signaling Pathway and Its Role in Cholangiocarcinoma Metastasis

Novel approaches in search for biomarkers of cholangiocarcinoma

Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients

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