ISSN / EISSN : 1949-2553 / 1949-2553
Current Publisher: Impact Journals, LLC (10.18632)
Total articles ≅ 26,118
Latest articles in this journal
Oncotarget, Volume 12, pp 878-890; doi:10.18632/oncotarget.27949
Oncotarget, Volume 12, pp 948-949; doi:10.18632/oncotarget.27444
Oncotarget, Volume 12, pp 891-906; doi:10.18632/oncotarget.27933
Oncotarget, Volume 12, pp 719-720; doi:10.18632/oncotarget.27946
Oncotarget, Volume 12, pp 723-725; doi:10.18632/oncotarget.27918
Oncotarget, Volume 12, pp 767-782; doi:10.18632/oncotarget.27935
Approximately 15% of colorectal cancer (CRC) cases present with high levels of microsatellite instability (MSI-H). Bulk RNA-sequencing approaches have been employed to elucidate transcriptional differences between MSI-H and microsatellite stable (MSS) CRC tumors. These approaches are frequently confounded by the complex cellular heterogeneity of tumors. We performed single-cell deconvolution of bulk RNA-sequencing on The Cancer Genome Atlas colon adenocarcinoma (TCGA-COAD) dataset. Cell composition within each dataset was estimated using CIBERSORTx. Cell composition differences were analyzed using linear regression. Significant differences in abundance were observed for 13 of 19 cell types between MSI-H and MSS/MSI-L tumors in TCGA-COAD. This included a novel finding of increased enteroendocrine (q = 3.71E-06) and reduced colonocyte populations (q = 2.21E-03) in MSI-H versus MSS/MSI-L tumors. We were able to validate some of these differences in an independent biopsy dataset. By incorporating cell composition into our regression model, we identified 3,193 differentially expressed genes (q = 0.05), of which 556 were deemed novel. We subsequently validated many of these genes in an independent dataset of colon cancer cell lines. In summary, we show that some of the challenges associated with cellular heterogeneity can be overcome using single-cell deconvolution, and through our analysis we highlight several novel gene targets for further investigation.
Oncotarget, Volume 12, pp 783-790; doi:10.18632/oncotarget.27941
Purpose: The purpose of this study is to identify novel urine protein biomarkers of bladder cancer using a Luminex based screening platform.
Oncotarget, Volume 12, pp 845-858; doi:10.18632/oncotarget.27934
Somatic mutation signatures are an informative facet of cancer aetiology, however they are rarely useful for predicting patient outcome. The aim of this study is to evaluate the utility of a panel of 142 mutation-signature–associated metrics (P142) for predicting cancer progression in patients from a ‘TCGA PanCancer Atlas’ cohort. The P142 metrics are comprised of AID/APOBEC and ADAR deaminase associated SNVs analyzed for codon context, strand bias, and transitions/transversions. TCGA tumor-normal mutation data was obtained for 10,437 patients, representing 31 of the most prevalent forms of cancer. Stratified random sampling was used to split patients into training, tuning and validation cohorts for each cancer type. Cancer specific machine learning (XGBoost) models were built using the output from the P142 panel to predict patient Progression Free Survival (PFS) status as either “High PFS” or “Low PFS”. Predictive performance of each model was evaluated using the validation cohort. Models accurately predicted PFS status for several cancer types, including adrenocortical carcinoma, glioma, mesothelioma, and sarcoma. In conclusion, the P142 panel of metrics successfully predicted cancer progression status in patients with some, but not all cancer types analyzed. These results pave the way for future studies on cancer progression associated signatures.
Oncotarget, Volume 12, pp 823-844; doi:10.18632/oncotarget.27940
Hypoxia stimulates neoangiogenesis, promoting tumor outgrowth, and triggers the epithelial-mesenchymal transition (EMT), which bestows cells with mesenchymal traits and multi-lineage differentiation potential. Here, we investigated whether EMT can confer endothelial attributes upon carcinoma cells, augmenting tumor growth and vascularization. Following orthotopic implantation of MCF-7 human epithelial breast cancer cells into mice, tumors of different sizes were immunostained for markers of hypoxia and EMT. Larger tumors were well-vascularized with CD31-positive cells of human origin. Hypoxic regions, demarcated by HIF-1α staining, exhibited focal areas of E-cadherin loss and elevated levels of vimentin and the EMT-mediator FOXC2. Implantation of MCF-7 cells, co-mixed with human mammary epithelial (HMLE) cells overexpressing the EMT-inducer Snail, markedly potentiated tumor growth and vascularization, compared with MCF-7 cells injected alone or co-mixed with HMLE-vector cells. Intra-tumoral vessels contained CD31-positive cells derived from either donor cell type. FOXC2 knockdown abrogated the potentiating effects of HMLE-Snail cells on MCF-7 tumor growth and vascularization, and compromised endothelial transdifferentiation of mesenchymal cells cultured in endothelial growth medium. Hence, cells that have undergone EMT can promote tumor growth and neovascularization either indirectly, by promoting endothelial transdifferentiation of carcinoma cells, or directly, by acquiring an endothelial phenotype, with FOXC2 playing key roles in these processes.
Oncotarget, Volume 12, pp 740-755; doi:10.18632/oncotarget.27928
Additional prognostic and therapeutic biomarkers effective across different histological types of sarcoma are needed. Herein we evaluate expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with potential ties to both pathways, in sarcomas of different histological types. Immunohistochemical staining of a tissue microarray including 163 sarcomas and correlation with clinical data showed that elevated YAP and TAZ independently predict worse overall and progression-free survival, respectively. In the absence of p53 expression, combined TAZ and YAP expression adversely affect overall, progression free, and metastasis free survival more than TAZ or YAP activation alone. RABL6A independently predicted shorter time to metastasis and was positively correlated with p53, MDM2 and YAP expression, supporting a possible functional relationship between the biomarkers. Network analysis further showed that TAZ is positively correlated with MDM2 expression. The data implicate all five proteins as clinically relevant downstream players in the Hippo pathway. Finally, a novel inhibitor of MDM2 (MA242), effectively suppressed the survival of sarcoma cell lines from different histological types regardless of p53 status. These findings suggest both independent and cooperative roles for all five biomarkers across different histological types of sarcoma in predicting patient outcomes and potentially guiding future therapeutic approaches.