Frontiers in Immunology (Oct 2022)

Integrated profiling of endoplasmic reticulum stress-related DERL3 in the prognostic and immune features of lung adenocarcinoma

  • Lanlan Lin,
  • Lanlan Lin,
  • Lanlan Lin,
  • Guofu Lin,
  • Guofu Lin,
  • Guofu Lin,
  • Hai Lin,
  • Hai Lin,
  • Hai Lin,
  • Luyang Chen,
  • Luyang Chen,
  • Luyang Chen,
  • Xiaohui Chen,
  • Xiaohui Chen,
  • Xiaohui Chen,
  • Qinhui Lin,
  • Qinhui Lin,
  • Yuan Xu,
  • Yuan Xu,
  • Yuan Xu,
  • Yiming Zeng,
  • Yiming Zeng,
  • Yiming Zeng

DOI
https://doi.org/10.3389/fimmu.2022.906420
Journal volume & issue
Vol. 13

Abstract

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BackgroundDERL3 has been implicated as an essential element in the degradation of misfolded lumenal glycoproteins induced by endoplasmic reticulum (ER) stress. However, the correlation of DERL3 expression with the malignant phenotype of lung adenocarcinoma (LUAD) cells is unclear and remains to be elucidated. Herein, we investigated the interaction between the DERL3 and LUAD pathological process.MethodsThe Cancer Genome Atlas (TCGA) database was utilized to determine the genetic alteration of DERL3 in stage I LUAD. Clinical LUAD samples including carcinoma and adjacent tissues were obtained and were further extracted to detect DERL3 mRNA expression via RT-qPCR. Immunohistochemistry was performed to evaluate the protein expression of DERL3 in LUAD tissues. The GEPIA and TIMER website were used to evaluate the correlation between DERL3 and immune cell infiltration. We further used the t-SNE map to visualize the distribution of DERL3 in various clusters at the single-cell level via TISCH database. The potential mechanisms of the biological process mediated by DERL3 in LUAD were conducted via KEGG and GSEA.ResultsIt was indicated that DERL3 was predominantly elevated in carcinoma compared with adjacent tissues in multiple kinds of tumors from the TCGA database, especially in LUAD. Immunohistochemistry validated that DERL3 was also upregulated in LUAD tissues compared with adjacent tissues from individuals. DERL3 was preliminarily found to be associated with immune infiltration via the TIMER database. Further, the t-SNE map revealed that DERL3 was predominantly enriched in plasma cells of the B cell population. It was demonstrated that DERL3 high-expressed patients presented significantly worse response to chemotherapy and immunotherapy. GSEA and KEGG results indicated that DERL3 was positively correlated with B cell activation and unfolded protein response (UPR).ConclusionOur findings indicated that DERL3 might play an essential role in the endoplasmic reticulum-associated degradation (ERAD) process in LUAD. Moreover, DERL3 may act as a promising immune biomarker, which could predict the efficacy of immunotherapy in LUAD.

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