Evaluation of tumor microenvironmental immune regulation and prognostic in lung adenocarcinoma from the perspective of purinergic receptor P2Y13

Bioengineered. 2021 Dec;12(1):6286-6304. doi: 10.1080/21655979.2021.1971029.

Abstract

Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The 'immuneeconv' R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (P2RY13) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of P2RY13 and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of P2RY13 was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. P2RY13 expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, P2RY13 is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification.

Keywords: P2RY13; immune regulation; lung adenocarcinoma; prognosis; tumor microenvironmental.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / immunology
  • Adenocarcinoma of Lung* / mortality
  • Aged
  • Animals
  • Female
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / mortality
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Prognosis
  • Protein Interaction Maps / genetics
  • Protein Interaction Maps / immunology
  • Receptors, Purinergic P2* / genetics
  • Receptors, Purinergic P2* / immunology
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology

Substances

  • P2RY13 protein, human
  • P2ry13 protein, mouse
  • Receptors, Purinergic P2

Grants and funding

This study was supported by grants from the Key R&D Program of Gansu Provincial Department of Science and Technology [20YF3FA028], Gansu Health Industry Scientific Research Project [GSWSKY-2019-79], In-hospital Funded Project of Lanzhou University First Hospital [ldyyyn2018-21], The Science and Technology Project of Chengguan District, Lanzhou City [2020JSCX0044].