Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma

Zhang, Minglei; Liu, Yang; Kong, Daliang

doi:10.1016/j.jbo.2020.100331

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…Osteosarcoma is an aggressive tumor of bone and prone to DM, occurring in 15-40% of patients (22,23). Almost all deaths in patients with osteosarcoma are caused by DM (24,25). Once osteosarcoma patients develop DM, the OS decreases dramatically and the 5-year survival rate decreases to 20% (15,26).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

et al. 2021

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BackgroundOsteosarcoma is the most common bone cancer, mainly occurring in children and adolescents, among which distant metastasis (DM) still leads to a poor prognosis. Although nomogram has recently been used in tumor areas, there are no studies focused on diagnostic and prognostic evaluation of DM in primary osteosarcoma patients.MethodsThe data of osteosarcoma patients diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in osteosarcoma patients, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors of osteosarcoma patients with DM. We then established two novel nomograms and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultA total of 1,657 patients with osteosarcoma were included, and 267 patients (16.11%) had DM at the time of diagnosis. The independent risk factors for DM in patients with osteosarcoma include age, grade, T stage, and N stage. The independent prognostic factors for osteosarcoma patients with DM are age, chemotherapy and surgery. The results of ROC curves, calibration, DCA, and Kaplan–Meier (K-M) survival curves in the training, validation, and expanded testing sets, confirmed that two nomograms can precisely predict occurrence and prognosis of DM in osteosarcoma patients.ConclusionTwo nomograms are expected to be effective tools for predicting the risk of DM for osteosarcoma patients and personalized prognosis prediction for patients with DM, which may benefit clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

et al. 2021

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“…Additionally, ABCA2 is overexpressed in pediatric acute lymphoblastic leukemia and may contribute to multidrug resistance ( 50 ). B3GALT4 is involved in synthesizing GM1/GD1 gangliosides and has been identified as a prognostic marker for osteosarcoma and neuroblastoma ( 51 , 52 ). Our results also showed the inhibition of B3GALT4 could significantly increase neuroblastoma cell proliferation, migration, and invasion in vitro .…”

Section: Discussionmentioning

confidence: 99%

A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response

et al. 2022

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IntroductionGangliosides play an essential role in cancer development and progression. However, the involvement of gangliosides in the prognosis and tumor microenvironment (TME) of neuroblastoma is not entirely understood.MethodsConsensus clustering analysis was performed to identify ganglioside-mediated molecular subtypes. LASSO-Cox analysis was conducted to identify independent prognostic genes, and a novel risk signature was constructed. The risk signature was validated internally and externally. We further explored the independent prognosis value, immune landscape, drug susceptibility, and tumor dedifferentiation of the risk signature. The role of the signature gene B3GALT4 in neuroblastoma was explored in vitro.ResultsSeventeen ganglioside-related genes were differentially expressed between INSS stage 4 and other stages, and two ganglioside-related clusters with distinct prognoses were identified. A novel risk signature integrating ten ganglioside-related prognostic genes was established. Across the train set and external validation sets, the risk signature presented high predictive accuracy and discrimination. The risk signature was an independent prognostic factor and constructed a nomogram combining multiple clinical characteristics. In the high-score group, the deficiency in antigen processing and presenting machinery, lack of immune cell infiltration, and escaping NK cells contributed substantially to immune escape. The low-score group was more responsive to immune checkpoint blockade therapy, while the high-score group showed substantial sensitivity to multiple chemotherapeutic drugs. Besides, the risk score was significantly positively correlated with the stemness index and reduced considerably in all-trans retinoic acid-treated neuroblastoma cell lines, indicating high dedifferentiation in the high-score group. Additionally, neuroblastoma cells with downregulation of B3GALT4 present with increased proliferation, invasion, and metastasis abilities in vitro.ConclusionThe novel ganglioside-related risk signature highlights the role of ganglioside in neuroblastoma prognosis and immune landscape and helps optimize chemotherapy and immunotherapy for neuroblastoma.

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“…Among these lncRNAs only LINC00957, AL035661.1, and EBLN3P had already been studied in cancer context. LINC00957 high expression was associated with bad prognosis in colorectal cancer (33) and osteosarcoma (34). The lncRNA AL035661.1 was found in a lncRNA profile that managed to efficiently predict early recurrence in hepatocellular carcinoma after curative resection (35) and was associated with EMT in Kidney renal clear cell carcinoma (36).…”

Section: Discussionmentioning

confidence: 99%

Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

et al. 2021

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Breast cancer (BRCA) is the most leading cause of cancer worldwide. It is a heterogeneous disease with at least five molecular subtypes including luminal A, luminal B, basal-like, HER2-enriched, and normal-like. These five molecular subtypes are usually stratified according to their mRNA profile patterns; however, ncRNAs are increasingly being used for this purpose. Among the ncRNAs class, the long non-coding RNAs (lncRNAs) are molecules with more than 200 nucleotides with versatile regulatory roles; and high tissue-specific expression profiles. The heterogeneity of BRCA can also be reflected regarding tumor microenvironment immune cells composition, which can directly impact a patient’s prognosis and therapy response. Using BRCA immunogenomics data from a previous study, we propose here a bioinformatics approach to include lncRNAs complexity in BRCA molecular and immune subtype. RNA-seq data from The Cancer Genome Atlas (TCGA) BRCA cohort was analyzed, and signal-to-noise ratio metrics were applied to create these subtype-specific signatures. Five immune-related signatures were generated with approximately ten specific lncRNAs, which were then functionally analyzed using GSEA enrichment and survival analysis. We highlighted here some lncRNAs in each subtype. LINC01871 is related to immune response activation and favorable overall survival in basal-like samples; EBLN3P is related to immune response suppression and progression in luminal B, MEG3, XXYLT1-AS2, and LINC02613 were related with immune response activation in luminal A, HER2-enriched and normal-like subtypes, respectively. In this way, we emphasize the need to know better the role of lncRNAs as regulators of immune response to provide new perspectives regarding diagnosis, prognosis and therapeutical targets in BRCA molecular subtypes.

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Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma

Cited by 13 publications

References 45 publications

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

Risk Factors, Prognostic Factors, and Nomograms for Distant Metastasis in Patients With Newly Diagnosed Osteosarcoma: A Population-Based Study

A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response

Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

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