BDNF Acts as a Prognostic Factor Associated with Tumor-Infiltrating Th2 Cells in Pancreatic Adenocarcinoma.

Yanan Zhu,Wenhua Li,Dongyan Zhao,Dongyu Zhao,Cangang Zhang,Shukun Yao,Zhe Zhao,Zhongqiu Xie

doi:10.1155/2021/7842035

Abstract

Pancreatic adenocarcinoma (PAAD) is an extremely lethal disease worldwide. Brain-derived neurotrophic factor (BDNF) is a critical member of the neurotrophin polypeptide superfamily that plays an important role in multiple cancers. However, the association among BDNF expression, tumor immunity, and PAAD prognosis remains unclear. BDNF expression and its influence on patient prognosis were explored based on The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and Kaplan-Meier plotter. Gene set enrichment analysis was performed to understand the biological roles of BDNF. The role of BDNF in tumor-infiltrating immune cells was determined using the Tumor Immune Estimation Resource database and the single-sample gene set enrichment analysis and xCell algorithm. The correlation among BDNF and chemokines, chemokine receptors, chemotherapeutic efficacy, and immune checkpoints was analyzed based on RStudio. BDNF expression was remarkably higher in PAAD compared to their paired normal tissues, and high BDNF expression was associated with unfavorable prognosis. Enrichment analysis revealed that BDNF was significantly enriched in major oncogenic pathways in PAAD. BDNF expression was positively correlated with immune infiltration, especially Th2 cells. Moreover, BDNF expression was positively correlated with Th2 cell-related chemokine/chemokine receptors, indicating that BDNF might modulate the migration of Th2 cells in PAAD. We also found that BDNF expression was correlated with high chemotherapeutics sensitivity and highly expressed immune checkpoints, making it a valuable biomarker in predicting the therapeutic benefits for chemotherapy and immunotherapy in cancer patients. In summary, BDNF might affect patient prognosis by interacting with tumor-infiltrating Th2 cells, thus serving as a potential prognostic biomarker in PAAD.

Highlights

Pancreatic adenocarcinoma (PAAD) is an extremely lethal disease found in the digestive system, ranking as the seventh leading cause of cancer-related death in both men and women worldwide [1]
We analyzed the gene expression profiles of Brain-derived neurotrophic factor (BDNF) in nearly 1000 human cancer cell lines extracted from the Cell Line Encyclopedia (CCLE) dataset, and the results revealed that the mRNA expression levels of BDNF were increased ubiquitously in contrast to the range of expression in the normal tissues and varied significantly among different cancer cell lines (Kruskal-Wallis test p = 8:2e − 33, Figure 1(b))
High mRNA expression of BDNF was noted in many cancer lines, especially those originating from the bone, pancreas, and pleura, whereas the relatively low expression was observed in the breast, intestine, and hematopoietic and lymphoid organs

Summary

Introduction

Pancreatic adenocarcinoma (PAAD) is an extremely lethal disease found in the digestive system, ranking as the seventh leading cause of cancer-related death in both men and women worldwide [1]. Multiagent conventional chemotherapy regimens are the mainstay of treatment for individuals diagnosed with advanced or metastatic PAAD, providing only months of overall survival (OS) benefit [3,4,5]. Such unfavorable clinical outcomes have fueled ongoing efforts to explore the complex feature of the tumor microenvironment (TME) and the molecular mechanisms underlying pancreatic carcinogenesis, Disease Markers and evidence has recently shown that immunotherapy targeting the interaction between tumor-infiltrating lymphocytes and tumor cells has been proposed as a promising therapy for PAAD [6, 7].

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