Dataset Information

Identification of a 3-gene signature based on differentially expressed invasion genes related to cancer molecular subtypes to predict the prognosis of osteosarcoma patients.

ABSTRACT: Invasion is a critical pathway leading to tumor metastasis. This study constructed an invasion-related polygenic signature to predict osteosarcoma prognosis. We initially determined two molecular subtypes of osteosarcoma, Cluster1 (C1) and Cluster2 (C2).. A 3 invasive-gene signature was established by univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis of the differentially expressed genes (DEGs) between the two subtypes, and was validated in internal and two external data sets (GSE21257 and GSE39058). Patients were divided into high- and low-risk groups by their signature, and the prognosis of osteosarcoma patients in the high-risk group was poor. Based on the time-independent receiver operating characteristic (ROC) curve, the area under the curve (AUC) for 1-year and 2-year OS were higher than 0.75 in internal and external cohorts. This signature also showed a high accuracy and independence in predicting osteosarcoma prognosis and a higher AUC in predicting 1-year osteosarcoma survival than other four existing models. In a word, a 3 invasive gene-based signature was developed, showing a high performance in predicting osteosarcoma prognosis. This signature could facilitate clinical prognostic analysis of osteosarcoma.

SUBMITTER: Wan Y

PROVIDER: S-EPMC8806416 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Identification of a 3-gene signature based on differentially expressed invasion genes related to cancer molecular subtypes to predict the prognosis of osteosarcoma patients.

Wan Yue Y Qu Ning N Yang Yang Y Ma Jing J Li Zhe Z Zhang Zhenyu Z

Bioengineered 20211201 1

Invasion is a critical pathway leading to tumor metastasis. This study constructed an invasion-related polygenic signature to predict osteosarcoma prognosis. We initially determined two molecular subtypes of osteosarcoma, Cluster1 (C1) and Cluster2 (C2).. A 3 invasive-gene signature was established by univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis of the differentially expressed genes (DEGs) between the two subtypes, and was validated ...[more]

PMID: 34488541

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Project description:BackgroundProstate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa.MethodsCuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4.ResultsTwo cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription.ConclusionThe cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.

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Dataset Information

Identification of a 3-gene signature based on differentially expressed invasion genes related to cancer molecular subtypes to predict the prognosis of osteosarcoma patients.

Publications

Identification of a 3-gene signature based on differentially expressed invasion genes related to cancer molecular subtypes to predict the prognosis of osteosarcoma patients.

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