The vascular landscape of human cancer

Kahn, Benjamin; Lucas, Alfredo; Alur, Rohan G.; Wengyn, Maximillian D.; Schwartz, Gregory W.; Li, Jinyang; Sun, Kevin; Maurer, H. Carlo; Olive, Kenneth P.; Faryabi, Robert B.; Stanger, Ben Z.

doi:10.1172/jci136655

Cited by 27 publications

(20 citation statements)

References 78 publications

(58 reference statements)

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“…Gene expression profiling at the single cell level across species and across tumors identified potential biomarkers of the endothelial cell tip phenotype, reflecting active SA [ 131 ]. A vascular microenvironment signature was associated retrospectively with response to bevacizumab [ 132 ].…”

Section: Discussionmentioning

confidence: 99%

Alternative Vascularization Mechanisms in Tumor Resistance to Therapy

Belotti

Pinessi

Taraboletti

2021

Cancers

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Blood vessels in tumors are formed through a variety of different mechanisms, each generating vessels with peculiar structural, molecular, and functional properties. This heterogeneity has a major impact on tumor response or resistance to antineoplastic therapies and is now emerging as a promising target for strategies to prevent drug resistance and improve the distribution and efficacy of antineoplastic treatments. This review presents evidence of how different mechanisms of tumor vessel formation (vasculogenesis, glomeruloid proliferation, intussusceptive angiogenesis, vasculogenic mimicry, and vessel co-option) affect tumor responses to antiangiogenic and antineoplastic therapies, but also how therapies can promote alternative mechanisms of vessel formation, contributing to tumor recurrence, malignant progression, and acquired drug resistance. We discuss the possibility of tailoring treatment strategies to overcome vasculature-mediated drug resistance or to improve drug distribution and efficacy.

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Section: Discussionmentioning

confidence: 99%

Alternative Vascularization Mechanisms in Tumor Resistance to Therapy

Belotti

Pinessi

Taraboletti

2021

Cancers

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“…In addition to GGT/ALT, there are many other biomarkers of vascular invasion, such as Vascular-endothelial cadherin (CDH5), Angiopoietin-2 (ANGPT2), ETS-related gene (ERG), etc. [ 36 ]. Relatively, serum GGT/ALT is easier to obtain and measure in clinical use.…”

Section: Discussionmentioning

confidence: 99%

Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC

Zhao

Zhu

et al. 2021

Cancer Cell Int

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Background The gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) ratio has been reported as an effective predictor of the severity of hepatitis and HCC. The purpose of this study was to determine the role of the GGT/ALT ratio in the prediction of vascular invasion and survival outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods The risk factors for vascular invasion were determined by univariate/multivariate logistic analysis. The cut-off value of GGT/ALT in predicting vascular invasion was calculated using the receiver operating characteristic (ROC) curve. The prognostic value of GGT/ALT was examined by Cox analysis and Kaplan–Meier curves. Sensitivity analysis, such as subgroup analysis and propensity score matching (PSM), was performed to reduce potential confounding bias. Results A high GGT/ALT ratio was identified as an independent risk factor for vascular invasion (P = 0.03). The correlation analysis suggested that higher GGT/ALT was associated with more severe tumour burdens, including vascular invasion (P < 0.001), tumour volume > 5 cm (P < 0.001), poor pathological differentiation (P = 0.042), more severe BCLC (P < 0.001) and ALBI grade (P = 0.007). In the survival analysis, a high GGT/ALT ratio was associated with poor overall survival (OS) (HR: 1.38; 95% CI 1.03, 1.87; P < 0.0001) and disease-free survival (DFS) (HR: 1.32; 95% CI 1.03, 1.87; P < 0.0001). In the subgroup analysis, similar results were consistently observed across most subgroups. In PSM analysis, GGT/ALT remained independently associated with vascular invasion (OR, 186; 95% CI 1.23, 3.33). Conclusion The GGT/ALT ratio was a potential effective factor in the prediction of vascular invasion and prognosis in patients with HBV-related HCC.

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“…Another TCGA study has identified six immune subtypes of SCCs including angiogenesis, while the molecular characteristics of angiogenesis were not fully uncovered [26]. Recently, Benjamin et al developed an endothelial index to estimate the vascular density of 31 solid tumor types and classified the human tumors into 6 vascular microenvironment signatures based on the 24 vascular "hub" genes [27]. While the different histology types of tumors present widely different patterns, our study only performed the analysis for SCCs and aimed to find out similar features for these types of tumors, providing the evidence for the personalized therapy.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of angiogenesis subtype of squamous cell carcinoma

et al. 2021

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Background Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated. Method and materials The angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed. Results A total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival). Conclusion Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.

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The vascular landscape of human cancer

Cited by 27 publications

References 78 publications

Alternative Vascularization Mechanisms in Tumor Resistance to Therapy

Alternative Vascularization Mechanisms in Tumor Resistance to Therapy

Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC

Comprehensive analysis of angiogenesis subtype of squamous cell carcinoma

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