As a highly aggressive bone malignancy, osteosarcoma poses a significant therapeutic challenge, especially in the setting of metastasis or recurrence. This study aimed to investigate the potential of CD8-Tex cell-associated genes as prognostic biomarkers to reveal the immunogenomic profile of osteosarcoma and guide therapeutic decisions. mRNA expression data and clinical details of osteosarcoma patients were obtained from the TCGA database (TARGET-OS dataset). The GSE21257 dataset (from the GEO database) was used as an external validation set to provide additional information on osteosarcoma specimens. 84 samples from the TARGET-OS dataset were used as the training set, and 53 samples from the GSE21257 dataset served as the external validation cohort. Univariate Cox regression analysis was utilized to identify CD8 Tex cell genes associated with prognosis. The LASSO algorithm was performed for 1000 iterations to select the best subset to form the CD8 Tex cell gene signature (TRS). Final genes were identified using the multivariate Cox regression model of the LASSO algorithm. Risk scores were calculated to categorize patients into high- and low-risk groups, and clinical differences were explored by Kaplan-Meier survival analysis to assess model performance. Prediction maps were constructed to estimate 1-, 3-, and 5 year survival rates for osteosarcoma patients, including risk scores for CD8 Texcell gene markers and clinicopathologic factors. The ssGSEA algorithm was used to assess the differences in immune function between TRS-defined high- and low-risk groups. TME and immune cell infiltration were further assessed using the ESTIMATE and CIBERSORT algorithms. To explore the relationship between immune checkpoint gene expression levels and the two risk-defined groups. A CD8 Tex cell-associated gene signature was extracted from the TISCH database and prognostic markers including two genes were developed. The high-risk group showed lower survival, and model performance was validated by ROC curves and C-index. Predictive plots were constructed to demonstrate survival estimates, combining CD8 Tex cell gene markers and clinical factors. This study provides valuable insights into the molecular and immune characteristics of osteosarcoma and offers potential avenues for advances in therapeutic approaches.
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http://dx.doi.org/10.1038/s41598-024-60539-z | DOI Listing |
Cell Rep
January 2025
The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China. Electronic address:
CD8 T cell exhaustion (Tex) has been widely acknowledged in human cancer, while the underlying mechanisms remain unclear. Here, we demonstrate that reduced amino acid (aa) metabolism and mTOR inactivation are accountable for Tex in human non-small cell lung cancer (NSCLC). NSCLC cells impede the T cell-intrinsic transcription of SLC7A5 and SLC38A1, disrupting aa transport and consequently leading to mTOR inactivation.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China; Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou 510060, China. Electronic address:
Purpose: To predict and evaluate the possible mechanisms and clinical value of ACTL6A in the prognosis and development of UM.
Methods: Bioinformatics analyze the relationship between ACTL6A and immunity in UM, which derived from TCGA, Gene Expression Omnibus (GEO) databases. Tumor-infltrated immune cells were demonstrated using QUANTISEQ and MCP-counter.
J Transl Med
December 2024
Department of Urology, Xinjiang Medical University Affiliated Cancer Hospital, Urumqi, China.
Background: Immune checkpoint inhibitors (ICIs) are a cornerstone therapy for advanced renal cell carcinoma (RCC). However, significant rates of primary resistance hinder their efficacy, and the underlying mechanisms remain poorly understood. This study aims to unravel the tumor-immune interactions and signaling pathways driving primary resistance to ICIs in RCC.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians University, Munich, Germany.
CD8+ T cells are crucial cytotoxic components of the tumor immune system. In chronic inflammation, they become low-responsive, a state known as T cell exhaustion (TEX). The aim of immune checkpoint blockade is to counteract TEX, yet its dynamics in breast cancer remain poorly understood.
View Article and Find Full Text PDFTransl Cancer Res
November 2024
Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent type of cancer with high incidence and mortality rates. It is the third most common cause of cancer-related deaths. CD8 T cell exhaustion (TEX) is a progressive decline in T cell function due to sustained T cell receptor stimulation from continuous antigen exposure.
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