Cyclophilin B overexpression predicts a poor prognosis and activates metastatic pathways in colon cancer

Xiaojing Zhang; Jinjing Tan; Lei Yang; Guangyu An

doi:10.21037/tcr-19-2960

Cyclophilin B overexpression predicts a poor prognosis and activates metastatic pathways in colon cancer

Transl Cancer Res. 2020 May;9(5):3573-3585. doi: 10.21037/tcr-19-2960.

Authors

Xiaojing Zhang¹, Jinjing Tan², Lei Yang³, Guangyu An¹

Affiliations

¹ Oncology Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
² Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
³ Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

Abstract

Background: Cyclophilin B (CypB) has been found overexpressed in various malignant tumors. To date, there are few studies on CypB in colon cancer. In this study, we aimed to analyze the CypB expression pattern and to further evaluate its clinical significance, especially its prognostic value for colon cancer.

Methods: CypB expression was investigated in colon cancer tissue microarrays (TMA) by RNAscope in situ hybridization and immunohistochemical (IHC) staining. The correlation between CypB and clinicopathological characteristics was analyzed. The Cancer Genome Atlas (TCGA) RNA-seq dataset of colon adenocarcinoma (COAD) was further analyzed to validate our main findings. Gene Set Enrichment Analysis (GSEA) and Search Tool for the Retrieval of Interacting Genes (STRING) analysis were performed to enrich CypB related biological pathways. In vitro experiments by knockdown of CypB in colon cancer cell HCT116 were performed to verify the bioinformatics results and analyze its role in the metastatic pathways in colon cancer.

Results: We found that CypB expression was highly upregulated in colon cancer tissues (P<0.05). Importantly, the overall survival (OS) time of patients with high CypB expression was significantly shorter than those with low CypB expression, and overexpressed CypB was identified as an independent prognostic indicator for poor survival (P=0.015). Subgroup analysis indicated that a high level of CypB was associated with a shorter OS time, especially for advanced cancer patients, such as later T stage, lymph node metastasis, larger tumor size (P<0.05). Analysis of TCGA RNA-seq dataset of COAD provided us with a larger clinical sample verification. Bioinformatics analysis and the following in vitro study revealed that CypB was involved in tumor metastatic associated signaling pathways.

Conclusions: CypB overexpression predicts a poor prognosis and may activate metastatic pathways in colon cancer.

Keywords: Colon cancer; RNAscope; cyclophilin B (CypB); metastasis; prognosis.