Integrating cell interaction with transcript factors to obtain a robust gene panel for prognostic prediction and therapies in cholangiocarcinoma

Research Square

Abstract

Abstract Background The efficacy of immunotherapy in cholangiocarcinoma (CCA) is blocked by its high degree of tumor heterogeneity. Methods We constructed empirical Bayes and Markov random field models to calculate transcription factors, interaction genes, and associated signaling pathways involved in cell-cell communication using single cell RNAseq data. Then, we analyzed the immune exhaustion mechanism in the CCA progression. Results We found that VEGFA positive macrophages with the high level of LGALS9 could interact with HAVCR2 to promote exhaustion of CD8 T cells in CCA. Transcript factors SPI1 and IRF1 could up-regulate the expression of LGALS9 in VEGFA positive macrophages. Subsequently, we obtained a panel containing 54 genes through the model, which could identify the subtype S2 with high expression of immune checkpoint genes that are suitable for immunotherapy. Moreover, we found that patients in subtype S2 with a higher mutation ratio of MUC16 accompanied with immune exhausted genes such as HAVCR2 and TIGIT. Finally, we constructed a nine-gene eLBP-LASSO-COX risk model which was designated as tumor microenvironment risk score (TMRS). Conclusions eLBP could simultaneously analyze the interaction genes, pathways and transcription factors involved in the cell communication. The TMRS panel was revealed to be a reliable tool for prognostic prediction and chemotherapeutic decision-making in cholangiocarcinoma.

Authors 10

1. Tingjie Wang

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

2. Chuanrui Xu

   First Affiliated Hospital of Xi'an Jiaotong University · Huazhong University of Science and Technology · Xi'an Jiaotong University

   Affiliation as printed

   Huazhong University of Science and Technology

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

3. Dan Xu

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

4. Xiaofei Yang

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   Genome Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

   School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

5. Yaxin Liu

   Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

6. Xiujuan Li

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

7. Zihang Li

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Xi’an Jiaotong University

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

8. Ningxin Dang

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   the First Affiliated Hospital of Xi’an Jiaotong University

   Genome Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China

9. Zhijing Zhang

   First Affiliated Hospital of Xi'an Jiaotong University · Huazhong University of Science and Technology · Xi'an Jiaotong University

   Affiliation as printed

   Huazhong University of Science and Technology

   Jiaotong University Ningxin Dang the First A liated Hospital of Xi'an Jiaotong University

   School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

10. Kai Ye corresponding Aachen Faculty of Science, Leiden University

    Leiden University · First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

    Affiliation as printed

    Xi’an Jiaotong University

    Faculty of Science, Leiden University, Leiden, the Netherlands

    Genome Institute, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

    MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

    School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

    School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

    School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China