Development and validation of a novel endoplasmic reticulum stress-related lncRNAs signature in osteosarcoma

Sep 21, 2026

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Osteosarcoma progression is shaped by long noncoding RNAs and by endoplasmic reticulum stress, yet the underlying mechanisms and clinically actionable biomarkers remain unclear. This study develops and validates an endoplasmic reticulum stress-related lncRNA (ERLs) prognostic signature to support survival prediction and therapy selection. Using UCSC Xena transcriptional and clinical data, LASSO and Cox regression generated a 5-lncRNA model, assessed through whole and validation cohorts. High-risk patients showed suppressed immune activation, reduced immune infiltration, and weaker immunotherapy responsiveness, with RT-qPCR supporting a reliable model; experiments indicate LINC02298 promotes invasion, migration, and proliferation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Background

Study aims and workflow

Data sources and ERS gene identification

Signature construction (LASSO and Cox)

Risk stratification analyses

Immune and drug-sensitivity evaluation

Experimental validation

ERLs prognostic signature

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Development and validation of a novel endoplasmic reticulum stress-related lncRNAs signature in osteosarcoma Peichuan Xu1,2, Jinghong Yuan1,2, Kaihui Li3, Yameng Wang1,2, Zhiwen Wu1,2, Jiangminghao Zhao1,2, Tao Li1,2, Tianlong Wu1, Xinxin Miao1, Dingwen He1 & Xigao Cheng1,2􀀍 Osteosarcoma (OS) is a cancerous tumor, and its development is greatly influenced by long noncoding RNA (lncRNA) . Endoplasmic reticulum stress (ERS) is an essential biological defense process in cells and contributes to the progression of tumors. However, the exact mechanisms remain elusive. This study aims to develop a signature of lncRNAs associated with ERS in OS. This signature will guide the prognosis prediction and the determination of appropriate treatment strategies. The UCSC Xena database collected transcriptional and clinical data of OS and muscle, after identifying ERS differentially expressed genes, we utilized correlation analysis to determine the endoplasmic reticulum stress lncRNAs (ERLs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were utilized to develop an ERLs signature. To clarify the fundamental mechanisms controlling gene expression in low and high-risk groups, Gene Set Variation Analysis (GSVA) were conducted. In addition, the distinction between the two groups regarding drug sensitivity and immune-related activity was investigated to determine the immunotherapy effects. Utilizing RT-qPCR, the expression of model lncRNAs in OS cell lines was ascertained. The functional analysis of LINC02298 was carried out through in vitro experiments and pan-cancer analysis. This study successfully constructed an ERLs prognostic signature for OS, which comprised 5 lncRNAs (AC023157.3, AL031673.1, LINC02298, LINC02328, SNHG26). The risk signature predicted overall survival inpatients with OS and was confirmed by assessing the validation and whole cohorts. Further, it was discovered that individuals classified as high-risk displayed suppressed immune activation, decreased infiltration of immune cells, and decreased responsiveness to immunotherapy. The RT-qPCR showed that the constructed risk prognosis model is reliable. Experimental validation has demonstrated that LINC02298 can promote OS cells’ invasion, migration, and proliferation. In addition, LINC02298 exhibited significant differential expression in many types of cancer. Moreover, LINC02298 is an important biomarker in a variety of tumors. This study established a novel ERLs signature, which successfully predicted the prognosis of OS. The function of LINC02298 in OS was elucidated via in vitro experiments. Therefore, it offers new opportunities for predicting the clinical prognosis of OS and establishes the basis for targeted therapy in OS. Abbreviations OS Osteosarcoma ER Endoplasmic reticulum ERS Endoplasmic reticulum stress ERGs Endoplasmic reticulum stress related genes ERLs Endoplasmic reticulum stress related lncRNAs LASSO Least absolute shrinkage and selection operator GO Gene ontology 1Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, China. 2Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang University, 330006 Nanchang, China. 3Center of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, China. 􀀍 email: [xigaocheng@hotmail.com](xigaocheng@hotmail.com) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) KEGG Kyoto encyclopedia of genes and genomes GSVA Gene set variation analysis ATCC American type culture collection MEM Minimal essential medium DMEM Dulbecco’s modified eagle medium FBS Fetal bovine serum cDNA Complementary DNA TME Tumor microenvironment IC50 Half-maximal inhibitory concentration SiRNA Small interfering RNA APC Antigen-presenting cells

FAQs

What is the main goal of the study on osteosarcoma?

To develop and validate a prognostic signature based on endoplasmic reticulum stress-related lncRNAs, enabling survival prediction and guidance for treatment strategy selection.

How was the ERLs signature constructed?

Transcriptional and clinical data were collected from UCSC Xena, ERS differentially expressed genes were identified, ER stress-related lncRNAs were determined by correlation analysis, and a 5-lncRNA signature was built using LASSO and Cox regression.

What biological differences were observed between high-risk and low-risk groups?

High-risk patients showed suppressed immune activation, decreased infiltration of immune cells, and reduced responsiveness to immunotherapy.

What experimental evidence supports the role of LINC02298 in osteosarcoma?

RT-qPCR confirmed expression changes, and functional in vitro experiments showed that LINC02298 promotes osteosarcoma cell invasion, migration, and proliferation.

Sep 21, 2026

Uploaded by Skyler