Journal Articles

Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915

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    Tumor mutational burden is a determinant of immune-mediated survival in breast cancer
    (Taylor and Francis, England, 2018-07-30) Thomas A; Routh ED; Pullikuth A; Jin G; Su J; Chou JW; Hoadley KA; Print C; Knowlton N; Black MA; Demaria S; Wang E; Bedognetti D; Jones WD; Mehta GA; Gatza ML; Perou CM; Page DB; Triozzi P; Miller LD
    Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). Tumor immune subclasses were associated with survival in patients with high TMB (TMB-Hi, P < 0.001) but not in those with low TMB (TMB-Lo, P = 0.44). This statistical relationship was confirmed in the METABRIC cohort (TMB-Hi, P = 0.047; TMB-Lo, P = 0.39), and also found to hold true in the more-indolent Luminal A tumor subtype (TMB-Hi, P = 0.011; TMB-Lo, P = 0.91). In TMB-Hi tumors, the FID subclass was associated with prolonged survival independent of tumor stage, molecular subtype, age and treatment. Copy number analysis revealed the reproducible, preferential amplification of chromosome 1q immune-regulatory genes in the PID immune subclass. These findings demonstrate a previously unappreciated role for TMB as a determinant of immune-mediated survival of breast cancer patients and identify candidate immune-regulatory mechanisms associated with immunologically cold tumors. Immune subtyping of breast cancers may offer opportunities for therapeutic stratification.
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    Development of a Nomogram to Predict the Outcome for Patients with Soft Tissue Sarcoma.
    (MDPI (Basel, Switzerland), 2023-03-29) Bray JP; Munday JS; Dobson J; Hayes A; Hughes K
    Soft tissue sarcomas (STSs) are common cutaneous or subcutaneous neoplasms in dogs. Most STSs are initially treated by surgical excision, and local recurrence may develop in almost 20% of patients. Currently, it is difficult to predict which STS will recur after excision, but this ability would greatly assist patient management. In recent years, the nomogram has emerged as a tool to allow oncologists to predict an outcome from a combination of risk factors. The aim of this study was to develop a nomogram for canine STSs and determine if the nomogram could predict patient outcomes better than individual tumour characteristics. The current study provides the first evidence in veterinary oncology to support a role for the nomogram to assist with predicting the outcome for patients after surgery for STSs. The nomogram developed in this study accurately predicted tumour-free survival in 25 patients but failed to predict recurrence in 1 patient. Overall, the sensitivity, specificity, positive predictive, and negative predictive values for the nomogram were 96%, 45%, 45%, and 96%, respectively (area under the curve: AUC = 0.84). This study suggests a nomogram could play an important role in helping to identify patients who could benefit from revision surgery or adjuvant therapy for an STS.
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    Immunostaining for VEGF and Decorin Predicts Poor Survival and Recurrence in Canine Soft Tissue Sarcoma.
    (MDPI (Basel, Switzerland), 2023-03-28) Bray JP; Perrott MR; Munday JS; van der Weyden L
    The aim of this study was to investigate whether using immunohistochemistry to detect the angiogenic proteins vascular endothelial growth factor (VEGF) and decorin can help predict the risk of local recurrence of, or death from, canine soft tissue sarcoma (STS). VEGF and decorin were detected using validated immunohistochemical methods on 100 formalin-fixed paraffin-embedded samples of canine STS. The tumours had been resected previously, with clinical outcome determined by questionnaire. Each slide was assessed by light microscopy and the pattern of immunostaining with VEGF and decorin determined. Patterns of immunostaining were then analysed to detect associations with outcome measures of local recurrence and tumour-related death. High VEGF immunostaining was significantly (p < 0.001) associated with both increased local recurrence and reduced survival time. The distribution of decorin immunostaining within the tumour was significantly associated with survival time (p = 0.04) and local tumour recurrence (p = 0.02). When VEGF and decorin scores were combined, STS with both high VEGF and low decorin immunostaining were more likely to recur or cause patient death (p < 0.001). The results of this study suggest that immunostaining of VEGF and decorin may help predict the risk of local recurrence of canine STS.