Written by | Xu Shuo, editor of | Zhou Yebin
Osteosarcoma is a malignant primary bone tumor that occurs in children, adolescents, and young adults. Osteosarcoma is malignant and lung metastases are common, making it the second most deadly tumor in children and adolescents. Despite the emergence of new treatment options over the past few decades, the five-year survival rate of osteosarcoma has barely improved, and it is still only 60 to 70 percent. Patients with early distal metastases had worse prognosis, with a five-year survival rate of less than 20 percent.
In recent years, there have been more and more studies showing that the immune response plays a crucial role in the occurrence and development of osteosarcoma. Immune genes regulate the body's immune response, while osteosarcoma can use immune-related genes to achieve immune escape and create a microenvironment suitable for tumor growth. Therefore, the important value of immune-related genes in the diagnosis and treatment of osteosarcoma deserves more in-depth study.
In October 2020, the Qiqi Xie team from the Department of Orthopedics of the Second Hospital of Lanzhou University published an article titled Discover of a novel immune-related genes prognostic signature for osteosarcoma in Nature scientific reports. By analyzing the clinical data and gene expression information in the TARGET and GTEx databases, 604 differentially expressed immune related genes (DEIRGs) associated with osteosarcoma and 10 key immune-related genes (HUB IRGs) were identified, and a prognostic marker consisting of 13 DEIRGs involved in osteosarcoma development was identified. It provides valuable information for predicting tumor prognosis and developing personalized treatment plans for patients in high-risk groups.
Studies in recent years have shown that osteosarcoma can use immune genes to escape detection by the immune system and create an environment for tumor growth. Studies have shown impaired immune function in the tumor microenvironment of osteosarcoma, reducing the immune system's ability to clear tumor cells. PI3K/AKT, MAPK and JAK-STAT are several cell pathways that are widely studied in patients with osteosarcoma, and the activation of these pathways is closely related to the growth and metastasis of osteosarcoma.
The 604 differentially expressed immune-related genes in this study are mainly involved in the regulation of cell chemotactin, leukocyte adhesion, and innate immunity. These genes are mainly present in the following signaling pathways: chemokines, PI3K/AKT, MAPK, JAK-STAT pathways, and NK cell-mediated cytotoxicity pathways.
Functional distribution of 604 differentially expressed immune-related genes (A) and the main signaling pathway (B)
The researchers identified 10 hub genes through protein interaction analysis: CXCR4, CCR5, CXCL16, CCL5, CXCL12, CXCL10, CXCR3, OPRL1, S1PR1, and GAL. The few genes that interact with other proteins at their core are CCR5, CXCL12, and CXCR4.
In these genes, OPRL1 encodes the endorphin receptor protein, and its high expression in osteosarcoma may be associated with cancer pain. SIPR1 encodes a receptor protein similar to the G protein-coupled receptor. Studies of lung, ovarian, and colon cancers have found that when they bind to SIP ligands, tumor growth, invasion, and metastasis are enhanced.
Therefore, researchers believe that it also plays an important role in the development of osteosarcoma. The CCR5, CXCL12, and CXCR4 genes edit chemokines or their receptors, thus influencing the tumorigenesis microenvironment.
Through the interaction analysis of proteins, the 10 hub genes at the core were identified
The main functions of the 10 Hub genes: widely involved in the regulation and immune escape of osteosarcoma occurrence and metastasis, and are associated with clinical symptoms such as pain in osteosarcoma.
The study further clarified a "prognostic marker" containing 13 IRGS. The team first screened out 82 immune-related genes associated with prognosis through regression analysis, and further clarified the markers consisting of 13 IRGS. RoC curve analysis showed that this prognostic marker had a high rate of correctness for the prognosis of osteosarcoma (AUC=0.918). And this prognostic marker can more accurately reflect prognosis than the biomarkers currently used (SP140, MALAT1, UCA1, MIRI191).
It is worth mentioning that the IRGS markers identified in this study are independent of the clinical conditions of age, sex, and transfer, making them a good prognostic marker.
The prognosis of osteosarcoma can be predicted by 13 marker genes
This article describes the immune-related genes that are differentially expressed relative to normal tissues in osteosarcoma, while extracting a set of genetic markers that may potentially be used to predict prognosis. Many of the genes found in the study coincided with the genes previously believed to be related to osteosarcoma immune escape, which verified the importance of the immune response in the occurrence and development of osteosarcoma, and also provided direction for related functional research.
Previous studies have found many biomarkers associated with osteosarcoma prognosis, but most of them are based on the study of individual genes, but the occurrence and development of tumors is not the result of single gene regulation, but the product of multiple gene interactions. Individual differences also lead to the inevitable limitations of single-gene studies, which also have limited sample sizes.
Through the statistical analysis of a large number of samples in the database, the prognostic marker composed of 13 immune-related genes was identified, which provided valuable information for clinical prognosis and precision treatment. This set of labels is more accurate than what is currently used, and if it can be verified in more clinical samples, there will be a wide range of applications.
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