Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients

Abstract

<jats:p>Prognosis of cholangiocarcinoma (CCA) patients is absolutely poor. Since improvement of prognosis and/or response to treatment by personalized and precision treatments requires earlier and precise diagnostic markers, discovery of prognostic markers attracts more attention. Apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) is highly expressed in several cancers including CCA. The present study investigated whether the serum AIFM3 level can be used as a potential marker for CCA prognosis. For this purpose, we first determined secretory protein nature of AIFM3 using bioinformatic tools. The results show that although AIFM3 lacks signal peptide, it can be secreted into plasma/serum via an unconventional pathway. Then, the AIFM3 levels in the sera of 141 CCA patients and 70 healthy controls (HC) were measured using a semi-quantitative dot blot assay. The results show that the AIFM3 level in the sera of CCA group was significantly higher than that of HC. When correlation between serum AIFM3 levels and the clinicopathological parameters of CCA patients were examined, serum AIFM3 levels correlated significantly with lymph node metastasis, age, and the patients’ overall survival (OS). Higher AIFM3 levels were significantly associated with shorter OS, and only AIFM3 was an independent prognostic marker for CCA. In conclusion, AIFM3 can be used as a prognostic marker for CCA.</jats:p>

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

“…For instance, HSP60 is primarily localized in the eukaryotic mitochondria and its overexpression in the sera is used as a biomarker for the diagnosis and prognosis of several cancers, including colorectal and breast cancers [29,30]. Recently, two mitochondrial proteins-PDK3 and AIFM3-in the sera have been determined and can be used as a prognostic marker for CCA [11,12]. The present results showed that CIAPIN1 is also a mitochondrial protein marker in the sera of CCA patients.…”

“…The Venn diagram indicated six CCA-related mitochondrial proteins, including nuclear receptor coactivator 1 isoform 3 (NCOA1), apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3), transitional endoplasmic reticulum ATPase (VCP), CIAPIN1, PRKCA-binding protein (PICK1), and peptidyl-prolyl cis-trans isomerase D (PPID). Among those, AIFM3 was excluded due to it already being detected in the sera of CCA and HC [12]. Tools in the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to evaluate the expression levels of the genes of these five proteins unique in CCA (Figure 1b-f).…”

Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells

“…The results shown above suggested potential roles of AIFM3 in migration and invasion of CCA cells. In our previous study, higher serum AIFM3 levels were significantly associated with lymph node metastasis and shorter overall survival of CCA patients (13). Here, we examined the expression of AIFM3 in CCA tissues with or without lymph node metastasis.…”

“…AIFM3 is highly expressed in breast cancer tissues and is significantly associated with the clinical outcome of breast cancer patients (25). Our recent study revealed that higher serum AIFM3 levels are associated with lymph node metastasis and shorter overall survival of patients with CCA (13). In this study, we intended to elucidate the biological roles of AIFM3 and the related signaling pathways in CCA.…”

“…AIFM3 was highly expressed in breast cancer tissues and was associated with lymph node metastasis and shorter OS/diseasefree survival (DFS) (25). Recently, we reported that serum AIFM3 levels were higher in CCA patients with lymph node metastasis compared to those without metastasis (13). Taking all these into account, AIFM3 expression in CCA tissues and/or serum can be useful for cancer prognosis.…”