Dataset Information

Non-Invasive Radiomics Approach Predict Invasiveness of Adamantinomatous Craniopharyngioma Before Surgery.

ABSTRACT:

Purpose

Craniopharyngiomas (CPs) are benign tumors, complete tumor resection is considered to be the optimal treatment. However, although histologically benign, the local invasiveness of CPs commonly contributes to incomplete resection and a poor prognosis. At present, some advocate less aggressive surgery combined with radiotherapy as a more reasonable and effective means of protecting hypothalamus function and preventing recurrence in patients with tight tumor adhesion to the hypothalamus. Hence, if a method can be developed to predict the invasiveness of CP preoperatively, it will help in the development of a more personalized surgical strategy. The aim of the study was to report a radiomics-clinical nomogram for the individualized preoperative prediction of the invasiveness of adamantinomatous CP (ACPs) before surgery.

Methods

In total, 1,874 radiomics features were extracted from whole tumors on contrast-enhanced T1-weighted images. A support vector machine trained a predictive model that was validated using receiver operating characteristic (ROC) analysis on an independent test set. Moreover, a nomogram was constructed incorporating clinical characteristics and the radiomics signature for individual prediction.

Results

Eleven features associated with the invasiveness of ACPs were selected by using the least absolute shrinkage and selection operator (LASSO) method. These features yielded area under the curve (AUC) values of 79.09 and 73.5% for the training and test sets, respectively. The nomogram incorporating peritumoral edema and the radiomics signature yielded good calibration in the training and test sets with the AUCs of 84.79 and 76.48%, respectively.

Conclusion

The developed model yields good performance, indicating that the invasiveness of APCs can be predicted using noninvasive radiological data. This reliable, noninvasive tool can help clinical decision making and improve patient prognosis.

SUBMITTER: Ma G

PROVIDER: S-EPMC7925821 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Non-Invasive Radiomics Approach Predict Invasiveness of Adamantinomatous Craniopharyngioma Before Surgery.

Ma Guofo G Kang Jie J Qiao Ning N Zhang Bochao B Chen Xuzhu X Li Guilin G Gao Zhixian Z Gui Songbai S

Frontiers in oncology 20210217

<h4>Purpose</h4>Craniopharyngiomas (CPs) are benign tumors, complete tumor resection is considered to be the optimal treatment. However, although histologically benign, the local invasiveness of CPs commonly contributes to incomplete resection and a poor prognosis. At present, some advocate less aggressive surgery combined with radiotherapy as a more reasonable and effective means of protecting hypothalamus function and preventing recurrence in patients with tight tumor adhesion to the hypothala ...[more]

PMID: 33680925

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Project description:Craniopharyngioma is a benign tumor, and the predominant treatment methods are surgical resection and radiotherapy. However, both treatments may lead to complex complications, seriously affecting patients' survival rate and quality of life. Adamantinomatous craniopharyngioma (ACP), as one of the histological subtypes of craniopharyngioma, is associated with a high incidence and poor prognosis, and there is a gap in the targeted therapy of immune-related genes for ACP. In this study, two gene expression profiles of ACP, namely GSE68015 and GSE94349, were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the Limma package, and 271 differentially expressed immune-related genes (DEIRGs) were obtained from the Immport database. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for annotation, visualization, and integrated discovery. Five hub genes, including CXCL6, CXCL10, CXCL11, CXCL13, and SAA1, were screened out through protein-protein interaction (PPI) network interaction construction. Two diagnostic markers, namely S100A2 and SDC1 (both of which have the Area Under Curve value of 1), were screened by the machine learning algorithm. CIBERSORT analysis showed that M2 macrophages, activated NK cells, and gamma delta T cells had higher abundance in ACP infiltration, while CD8+ T cells, regulatory T cells, and Neutrophils had less abundance in ACP infiltration. The expression of gamma delta T cells was positively correlated with CXCL6, S100A2, SDC1, and SAA1, while CD8+ T cells expression was negatively correlated with CXCL6, S100A2, SDC1, and CXCL10. ACP with high CXCL6 showed remarkable drug sensitivity to Pentostatin and Wortmannin via CellMiner database analysis. Our results deepened the understanding of the molecular immune mechanism in ACP and provided potential biomarkers for the precisely targeted therapy for ACP.

Project description:Background Adamantinoma craniopharyngioma (ACP) is a non-malignant tumour of unknown pathogenesis that frequently occurs in children and has malignant potential. The main treatment options are currently surgical resection and radiotherapy. These treatments can lead to serious complications that greatly affect the overall survival and quality of life of patients. It is therefore important to use bioinformatics to explore the mechanisms of ACP development and progression and to identify new molecules. Methods Sequencing data of ACP was downloaded from the comprehensive gene expression database for differentially expressed gene identification and visualized by Gene Ontology, Kyoto Gene, and gene set enrichment analyses (GSEAs). Weighted correlation network analysis was used to identify the genes most strongly associated with ACP. GSE94349 was used as the training set and five diagnostic markers were screened using machine learning algorithms to assess diagnostic accuracy using receiver operating characteristic (ROC) curves, while GSE68015 was used as the validation set for verification. Results Type I cytoskeletal 15 (KRT15), Follicular dendritic cell secreted peptide (FDCSP), Rho-related GTP-binding protein RhoC (RHOC), Modulates negatively TGFB1 signaling in keratinocytes (CD109), and type II cytoskeletal 6A (KRT6A) (area under their receiver operating characteristic curves is 1 for both the training and validation sets), Nomograms constructed using these five markers can predict progression of ACP patients. Whereas ACP tissues with activated T-cell surface glycoprotein CD4, Gamma delta T cells, eosinophils and regulatory T cells were expressed at higher levels than in normal tissues, which may contribute to the pathogenesis of ACP. According to the analysis of the CellMiner database (Tumor cell and drug related database tools), high CD109 levels showed significant drug sensitivity to Dexrazoxane, which has the potential to be a therapeutic agent for ACP. Conclusions Our findings extend understandings of the molecular immune mechanisms of ACP and suggest possible biomarkers for the targeted and precise treatment of ACP.

Project description:Purpose:Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis. Results:Patient DNA was sequenced using Ion PI v3 chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3'-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants. Conclusion:As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.

Dataset Information

Non-Invasive Radiomics Approach Predict Invasiveness of Adamantinomatous Craniopharyngioma Before Surgery.

Purpose

Methods

Results

Conclusion

Publications

Non-Invasive Radiomics Approach Predict Invasiveness of Adamantinomatous Craniopharyngioma Before Surgery.

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