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多聚免疫球蛋白受体(pIgR)在癌症中的作用。

Polymeric immunoglobulin receptor (pIgR) in cancer.

机构信息

Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

J Cancer Res Clin Oncol. 2023 Dec;149(19):17683-17690. doi: 10.1007/s00432-023-05335-4. Epub 2023 Oct 28.

Abstract

BACKGROUND

The polymeric immunoglobulin receptor (pIgR) is a transmembrane transporter of polymeric IgA through the intestinal epithelium. Its overexpression has been reported in several cancers, but its role as a diagnostic and prognostic biomarker of oncogenesis is currently unclear.

METHOD

A literature search was conducted to summarize the functions of pIgR, its expression levels, and its clinical implications.

RESULTS

pIgR expression has previously been investigated by proteomic analysis, RNA sequencing, and tissue microarray at the level of both RNA and protein in various cancers including pancreatic, esophageal, gastric, lung, and liver. However, studies have reported inconsistent results on how pIgR levels affect clinical outcomes such as survival rate and chemotherapy resistance. Possible explanations include pIgR mRNA levels being minimally correlated with the rate of downstream pIgR protein synthesis, and the diversity of antibodies used in immunohistochemistry studies further magnifying this ambiguity. In ovarian cancer cells, the transcytosis of IgA accompanied a series of transcriptional changes in intracellular inflammatory pathways that inhibit the progression of cancer, including the upregulation of IFN-gamma and downregulation of tumor-promoting ephrins. These findings suggest that both the levels of pIgR and secreted IgA from tumor-infiltrating B cells affect clinical outcomes.

CONCLUSION

Overall, no direct correlation was observed between the levels of pIgR inside tumor tissue and the clinical features in cancer patients. Measuring pIgR protein levels with a more specific and possibly chemically defined antibody, along with tumoral IgA, is a potential solution to better understand the pathways and consequences of pIgR overexpression in cancer cells.

摘要

背景

多聚免疫球蛋白受体(pIgR)是一种跨膜转运体,可将多聚 IgA 转运穿过肠上皮细胞。其在几种癌症中的过表达已被报道,但作为癌症发生的诊断和预后生物标志物的作用目前尚不清楚。

方法

进行文献检索,以总结 pIgR 的功能、表达水平及其临床意义。

结果

以前已经在各种癌症中(包括胰腺、食管、胃、肺和肝)通过蛋白质组分析、RNA 测序和组织微阵列在 RNA 和蛋白质水平上研究了 pIgR 的表达。然而,关于 pIgR 水平如何影响生存率和化疗耐药等临床结局的研究结果不一致。可能的解释包括 pIgR mRNA 水平与下游 pIgR 蛋白合成的速率之间相关性极小,以及免疫组织化学研究中使用的抗体多样性进一步放大了这种不确定性。在卵巢癌细胞中,IgA 的转胞吞作用伴随着一系列抑制癌症进展的细胞内炎症途径的转录变化,包括 IFN-γ的上调和促进肿瘤的 ephrins 的下调。这些发现表明,肿瘤浸润 B 细胞的 pIgR 和分泌的 IgA 水平都影响临床结局。

结论

总体而言,肿瘤组织内 pIgR 水平与癌症患者的临床特征之间没有直接相关性。使用更特异和可能化学定义的抗体测量 pIgR 蛋白水平,以及肿瘤 IgA,是更好地理解癌症细胞中 pIgR 过表达的途径和后果的潜在解决方案。

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