Abstract
Pancreatic adenocarcinoma (PAAD) is the 10th most common cancer worldwide and the outcomes for patients with the disease remain extremely poor. Precision biomarkers are urgently needed to increase the efficiency of early diagnosis and to improve the prognosis of patients. The tumor microenvironment (TME) and tumor immune infiltration are thought to impact the occurrence, progression, and prognosis of PAAD. Novel biomarkers excavated originating from the TME and immune infiltration may be effective in predicting the prognosis of PAAD patients. In the current study, the ESTIMATE and CIBERSORT algorithms were applied to estimate the division of immune and stromal components and the proportion of tumor-infiltrating immune cells in 182 PAAD cases downloaded from The Cancer Genome Atlas database. Intersection analyses of the Protein-Protein Interaction networks and Cox regression analysis identified the chemokine (CXC-motif) ligand 10 (CXCL10) as a predictive biomarker. We verified that CXCL10 in the TME negatively correlates with prognosis in PAAD and positively correlates with tumor cell differentiation. GSE62452 from the GEO database and cumulative survival analysis were performed to validate CXCL10 expression as an independent prognostic indicator. We also found that memory B cells, regulatory T cells, and macrophages M0 and M1 were correlated with the expression of CXCL10 indicating that expression of CXCL10 influenced the immune activity of the TME. Our data suggest that CXCL10 is beneficial as a prognostic indicator in PAAD patients and highlights the potential for immune targeted therapy in the treatment of PAAD.
Highlights
Pancreatic adenocarcinoma (PAAD) is one of the most deadly malignant tumors and is ranked the seventh leading cause of cancer death (n 432,000) (Bray et al, 2018)
The fractions of tumor infiltrated immune cells and proportions of the immune and stromal component in the 182 cases of PAAD downloaded from TCGA were evaluated using the ESTIMATE and CIBERSORT algorithms
We found that CXCL10 was closely associated with the prognosis of PAAD patients
Summary
Pancreatic adenocarcinoma (PAAD) is one of the most deadly malignant tumors and is ranked the seventh leading cause of cancer death (n 432,000) (Bray et al, 2018). The TME consists of the extracellular matrix, soluble molecules, and tumor stromal cells (Thomas and Radhakrishnan, 2019). Multiple studies have demonstrated that the TME can improve the invasiveness of tumor cells by modulating proliferation, chemotherapy resistance, immune escape, and metastasis Immune and stromal cells are the two main types of nontumor components in TME which have been considered to be valuable for tumor diagnosis and prognosis evaluation (Wörmann et al, 2014; Xu et al, 2014). Several studies have demonstrated the role of stromal cells in extracellular matrix remodeling and tumor angiogenesis. The regulatory mechanisms of immune cells, stromal components of TME, and tumor immune infiltration in PAAD remain largely unknown
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
