Assessing the prognostic value of SIL1 in pancancer cohorts and its practical application as a biomarker in glioma practice

Sep 23, 2026

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Gliomas are aggressive brain tumors with poor outcomes, and the endoplasmic reticulum chaperone factor SIL1 remains insufficiently characterized in glioma pathogenesis. This study used pan-cancer multi-omics analyses of TCGA and GTEx to evaluate SIL1 expression, prognostic significance, and links to genomic instability, tumor stemness, and immune infiltration. Functional validation in U251 and A172 glioma cells tested proliferation, migration, apoptosis, and EMT after siRNA knockdown and lentiviral rescue. Elevated SIL1 marked worse survival, higher heterogeneity, stemness, and an immunosuppressive milieu, while knockdown suppressed malignant phenotypes and EMT.

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CategoryHealthcare

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Abstract

Background

Methods

Results

Conclusion

Introduction

Liu et al. BMC Cancer (2026) 26:1004 BMC Cancer [https://doi.org/10.1186/s12885-026-16241-6](https://doi.org/10.1186/s12885-026-16241-6) RESEARCH Open Access Assessing the prognostic value of SIL1 in pancancer cohorts and its practical application asa biomarker in glioma practice Peiru Liu1,2†, Yao Peng1,2†, Ying Sun2†, Shenghui Hu2, Dongyang Lv2* and Ying Yan2* Abstract Background Gliomas are aggressive brain tumors associated with a poor prognosis. Although SIL1, an endoplasmic reticulum chaperone factor, is known to maintain protein homeostasis, its specific role in glioma pathogenesis remains poorly understood. This study aimed to investigate the clinical significance and biological functions of SIL1 in glioma. Methods We performed a pan-cancer multi-omics analysis using TCGA and GTEx datasets to evaluate SIL1 expression, its prognostic value, and its associations with genomic instability, tumor stemness, and immune infiltration. Gene set enrichment analysis (GSEA) was utilized to identify potentially involved signaling pathways. For in vitro functional validation, human glioma cell lines (U251 and A172) were subjected to siRNA-mediated knockdown and lentiviral rescue assays to assess cellular proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) dynamics. Results SIL1 was significantly upregulated in gliomas and correlated with poor patient survival. High SIL1 expression was associated with increased tumor heterogeneity (based on MATH scores), DNA methylation-derived stemness indices, and an immunosuppressive microenvironment characterized by the enrichment of M2 macrophages, regulatory T cells (Tregs), and immune checkpoint molecules. In vitro, SIL1 knockdown suppressed glioma cell proliferation and invasion, promoted mitochondrial apoptosis, and mitigated the EMT phenotype, potentially by impairing SNAIL nuclear translocation. Notably, these phenotypic changes were effectively rescued following lentiviral overexpression of SIL1 . Conclusion Our findings suggest that SIL1 is a potential prognostic biomarker in glioma. Its elevated expression correlates with increased malignancy, stemness features, EMT, and an immunosuppressive microenvironment, indicating that SIL1 may serve as a promising therapeutic target for glioma intervention. Keywords SIL1, Glioma, Pan-cancer analysis, Immune microenvironment, EMT, Prognostic biomarker †Peiru Liu, Yao Peng andYing Sun contributed equally to this work. *Correspondence: Dongyang Lv [Dongyanglv@sina.com](Dongyanglv@sina.com) Ying Yan [yanyingdoctor@sina.com](yanyingdoctor@sina.com) 1Dalian Medical University, Dalian 116000, China 2Department of Radiation Oncology, General Hospital of Northern Theater Command, Shenyang 110016, China © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Liu et al. BMC Cancer (2026) 26:1004 Introduction Malignant neopl

FAQs

What was the primary objective of the SIL1 study in glioma?

To determine SIL1’s clinical significance and biological functions in glioma, including whether it can serve as a prognostic biomarker.

How were SIL1 expression and prognostic value evaluated?

Using pan-cancer multi-omics analysis with TCGA and GTEx datasets to assess expression patterns and prognostic associations.

What effects did SIL1 knockdown have on glioma cells?

SIL1 knockdown suppressed glioma cell proliferation and invasion, promoted mitochondrial apoptosis, and mitigated EMT features, with effects rescued by lentiviral SIL1 overexpression.

Sep 23, 2026

Uploaded by nayy☆