Scholarlink

Background <p>KDELR2, a retrograde transport receptor involved in ER protein homeostasis, has emerged as a potential contributor to cancer development. However, its comprehensive expression profile and immunological roles across diverse human tumors remain unclear.</p> Methods <p>We performed an integrative pan-cancer analysis of KDELR2 using the TCGA and GTEx datasets, and examined its expression patterns, genetic alterations, methylation status, prognostic significance, and associations with immune infiltration and hallmark cancer pathways. Functional insights were derived from GSEA, GSVA, and immune landscape analyses. Wound healing, transwell and sphere formation assays were performed to investigate the role of KDELR2 in the stem-like properties, migration and invasion of pancreatic cancer cells.</p> Results <p>KDELR2 was broadly overexpressed in various tumor types and significantly associated with advanced tumor stages and poor clinical outcomes. Copy number amplification was the predominant genomic alteration, while promoter hypomethylation also contributed to its dysregulation. KDELR2 expression was correlated with the activation of oncogenic pathways, including those related to the ER stress response, glycosylation, and membrane trafficking. Moreover, KDELR2 was linked to immunosuppressive microenvironmental features, including enrichment of Tregs, TAMs, and MDSCs and reduced infiltration of cytotoxic immune cells. These trends were validated across multiple immune databases. KDELR2 also showed strong associations with immune checkpoint molecules and chemokine signaling networks, suggesting a dual role in tumor progression and immune evasion. Additionally, in vitro experiments revealed that KDELR2 overexpression promoted the stem-like properties, migration and invasion of PANC-1 cells, whereas KDELR2 knockdown led to the opposite results.</p> Conclusion <p>KDELR2 serves as a potential pan-cancer biomarker associated with tumor aggressiveness and immune modulation. Our findings support KDELR2 as a promising candidate for prognostic evaluation and targeted intervention, particularly in the context of immunotherapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A pan-cancer analysis of the oncogenic role of KDELR2 in human cancers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月18日

查看全文
  • Yu Xie,
  • Dong Chen,
  • Qi Zhang

摘要

Background

KDELR2, a retrograde transport receptor involved in ER protein homeostasis, has emerged as a potential contributor to cancer development. However, its comprehensive expression profile and immunological roles across diverse human tumors remain unclear.

Methods

We performed an integrative pan-cancer analysis of KDELR2 using the TCGA and GTEx datasets, and examined its expression patterns, genetic alterations, methylation status, prognostic significance, and associations with immune infiltration and hallmark cancer pathways. Functional insights were derived from GSEA, GSVA, and immune landscape analyses. Wound healing, transwell and sphere formation assays were performed to investigate the role of KDELR2 in the stem-like properties, migration and invasion of pancreatic cancer cells.

Results

KDELR2 was broadly overexpressed in various tumor types and significantly associated with advanced tumor stages and poor clinical outcomes. Copy number amplification was the predominant genomic alteration, while promoter hypomethylation also contributed to its dysregulation. KDELR2 expression was correlated with the activation of oncogenic pathways, including those related to the ER stress response, glycosylation, and membrane trafficking. Moreover, KDELR2 was linked to immunosuppressive microenvironmental features, including enrichment of Tregs, TAMs, and MDSCs and reduced infiltration of cytotoxic immune cells. These trends were validated across multiple immune databases. KDELR2 also showed strong associations with immune checkpoint molecules and chemokine signaling networks, suggesting a dual role in tumor progression and immune evasion. Additionally, in vitro experiments revealed that KDELR2 overexpression promoted the stem-like properties, migration and invasion of PANC-1 cells, whereas KDELR2 knockdown led to the opposite results.

Conclusion

KDELR2 serves as a potential pan-cancer biomarker associated with tumor aggressiveness and immune modulation. Our findings support KDELR2 as a promising candidate for prognostic evaluation and targeted intervention, particularly in the context of immunotherapy.