Apolipoprotein B Is Associated With the Microenvironment of Cholangiocarcinoma

Abstract

BackgroundCholangiocarcinoma (CCA) is a kind of devastating malignancy, which is correlated with the extremely high mortality. Due to the occult pathogenesis of CCA, most patients are diagnosed in the advanced stage. However, the efficacy of chemotherapy and immunotherapy is limited for these patients. The cause for this phenomenon is unclear, the recent researches indicate that it could be related to predisposing genetic factors and tumor microenvironment (TME) changes. The TME is created by the tumor and dominated by tumor-induced interactions. And the tumor prognosis could be influenced by the extent of infiltrating immune cells and stromal cells in TME.Materials and methodsThe abundance ratio of immune cells for each sample was obtained via the CIBERSORT algorithm, and we used ESTIMATE score system to calculate the immune and stromal scores in CCA. The CCA cases in TCGA database were categorized into high and low score groups according to their immune/stromal scores. And then, we identified the differential expressed genes (DEGs) in two groups. Functional enrichment analysis and protein‐protein interaction networks were carried out for DEGs. Interestingly, we found out that apolipoprotein B (APOB) is the most down-regulated among these genes. Then we performed the immunohistochemistry staining of APOB in a CCA tumor microarray which contained 100 CCA cases, APOB was down-regulated in CCA samples. Thus, we evaluated the APOB function in the TME of CCA through TIMER.Results and ConclusionThe results demonstrate that the infiltration degree of immune cells in CCA could be influenced by the expression of APOB, and the APOB expression could be mediated by DNA methylation. Our study not only indicates APOB is a potential target for CCA immunotherapy but also provides new ideas for researchers to explore the immunotherapy of various tumors.

Integrated weighted gene co‐expression network analysis reveals biomarkers associated with prognosis of high‐grade serous ovarian cancer

“…Meanwhile, APOB also might be associated with the immune cell infiltration in cholangiocarcinoma. 40 SERPINA1 is a serine protease inhibitor belonging to the serpin surperfamily, elevated level of which is related to the invasive potential of gastric, lung and colorectal adenocarcinoma, 41 , 42 , 43 On the contrary, other studies have proved that SERPINA1 is significantly downregulated in a variety of cancers, and patients with high expression of SERPINA1 have a longer overall survival than patients with low expression, showing an anti‐cancer effect. 44 , 45 , 46 The above completely opposite effects of APOB and SERPINA1 on predicting prognosis of tumors indicate the complexity of tumorigenesis and tumor development.…”

Alterations in Gene Pair Correlations as Potential Diagnostic Markers for Colon Cancer

“…APOA1 was reported to be associated with anti-inflammatory, antiangiogenic [ 54 ], immunoregulatory [ 55 , 56 ], and antithrombotic [ 57 , 58 ] activities. Although no association was found between colon cancer and APOB and APOC3 expressions, a recent report evaluated the role of APOB in bile duct cancer and demonstrated that APOB influences the infiltration degree of immune cells [ 59 ]. Furthermore, APOC3 is involved in the breakdown of triglycerides, and hence its plasma level directly correlates with the plasma triglyceride level [ 60 ].…”

APOB is a potential prognostic biomarker in hepatocellular carcinoma

“…Furthermore, our study highlights the importance of immune checkpoint expression and adequate immune cell infiltration in enhancing the effectiveness of immunotherapy [ 76 – 80 ]. Therefore, we assessed the association between APOB and immune checkpoints.…”