Journal OncoTargets and Therapy-
OncoTargets and Therapy, Volume 12, pp 2123-2136; doi:10.2147/ott.s194138
Abstract:Research status and progress of the RNA or protein biomarkers for prostate cancer
OncoTargets and Therapy; doi:10.2147/ott
Abstract:An international, peer-reviewed journal focusing on the pathological basis of all cancers, potential targets for therapy and treatment protocols employed to improve the management of cancer patients. In terms of therapy, palliative care is also included as part of the overall patient careÂ process.
OncoTargets and Therapy, Volume 12, pp 2115-2121; doi:10.2147/ott.s196725
Abstract:SUVmax and metabolic tumor volume: surrogate image biomarkers of KRAS mutation status in colorectal cancer
OncoTargets and Therapy, Volume 12, pp 1965-1977; doi:10.2147/ott.s196430
Abstract:Downregulation of MMSET impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling
OncoTargets and Therapy, Volume 12, pp 1947-1956; doi:10.2147/OTT.S186922
Abstract:To explore the effects of hypoxic non-small-cell lung cancer (NSCLC)-derived exosomes on NSCLC resistance to cisplatin. Exosomes were isolated by differential centrifugation and characterized by transmission electron microscope and Western blotting. Quantitative real-time PCR was used to measure miR-21 levels. MTT assays and colony formation assays were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance. Hypoxic NSCLC cell-derived exosomes facilitate normoxic cell resistance to cisplatin. In addition, hypoxia enhanced the miR-21 expression in NSCLC cells and cell-derived exosomes. Interestingly, changes in miR-21 levels in the hypoxia-induced exosomes affected the sensitivity of recipient cells to cisplatin. Mechanically, exosomal miR-21 promoted cisplatin resistance by downregulating phosphatase and tensin homolog (PTEN). The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN. Moreover, high miR-21 expression was associated with shorter median survival period in patients undergoing pharmacotherapy, but no association was observed in patients who were not under pharmacotherapy. Exosomal miR-21 derived from hypoxic NSCLC cells may promote cisplatin resistance, which indicates that exosomal miR-21 might be a potential biomarker and therapeutic target to address NSCLC chemoresistance.
OncoTargets and Therapy, Volume 12, pp 1957-1964; doi:10.2147/OTT.S192631
Abstract:To date, curative resection remains to be the most optimal therapeutic choice of hepatocellular carcinoma (HCC), though the overall survival (OS) remains extremely unsatisfactory. To better manage the HCC patients, we evaluated the prognosis predicting values of apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) on the long-time survival of patients who underwent surgical treatment in this study. A subgroup of 164 patients from our previously described follow-up cohort were enrolled in this study, of whom the pre-surgery ApoB and LDL-C measurements were available. They had been followed until January 2017, with a 19.5 months median survival time. The prognosis predicting values of serum ApoB, LDL-C, and other clinical variables were evaluated through Cox univariate and multivariate analyses, meanwhile, Kaplan–Meier analysis was conducted to obtain the OS curves. Pre-surgery ApoB was an independent prognosis predicting factor with HR as 1.396 (P=0.033), elevated ApoB was associated with worse postsurgery prognosis in HCC patients. Concordantly, Spearman’s correlation analysis revealed that value of pre-surgery ApoB was to some extent correlated with tumor size (r=0.355, P<0.001). In line with this, further univariate and multivariate logistic regression analysis revealed that patients with higher ApoB value were more likely to have larger tumor size (≥5 cm), with the OR value as high as 2.221 (95% CI: 1.288–3.830, P=0.004). Additionally, level of ApoB was found to be highly correlated with the serum level of LDL-C (r=0.686, P<0.001). ApoB could be a valuable novel prognosis predicting marker for HCC patients who underwent curative liver resection. Moreover, elevated ApoB level could indicate worse outcome in HCC patients, which could be explained by the relationship between ApoB and residual liver function.
OncoTargets and Therapy, Volume 12, pp 1937-1945; doi:10.2147/OTT.S191621
Abstract:Acute myeloid leukemia (AML) is a kind of malignant hematopoietic system disease characterized by abnormal proliferation, poor cell differentiation, and infiltration of bone marrow, peripheral blood, or other tissues. To date, the first-line treatment of AML is still based on daunorubicin and cytosine arabinoside or idarubicin and cytosine arabinoside regimen. However, the complete remission rate of AML is still not optimistic, especially in elderly patients, and the recurrence rate after complete remission is still high. The resistance of leukemia cells to chemotherapy drugs becomes the main obstacle in the treatment of AML. At present, the research on the mechanisms of drug resistance in AML is very active. This article will elaborate on the main mechanisms of drug resistance currently being studied, including drug resistance-related proteins and enzymes, gene alterations, micro RNAs, and signal pathways.
OncoTargets and Therapy, Volume 12, pp 1905-1915; doi:10.2147/OTT.S188134
Abstract:Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77–8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65–8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17–3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64–10.58; P=0.001). This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA.
OncoTargets and Therapy, Volume 12, pp 1917-1927; doi:10.2147/OTT.S190145
Abstract:The MYBL2 gene, a highly conserved member of the Myb transcription-factor family, has been implicated in the genesis and progression of many types of tumors. We analyzed the expression of MYBL2 and Ki67 in tissue samples of esophageal squamous-cell carcinoma (ESCC) patients by immunohistochemistry. We further analyzed the effect of MYBL2 on cell proliferation and DNA replication using a CCK8 assay, 5-ethynyl-2′-deoxyuridine–retention assay, flow-cytometry analysis, real-time quantitative PCR, Western blot, and a xenograft model of ESCC cells in nude mice. MYBL2 expression was significantly higher in ESCC tissue when compared to the adjacent normal tissue (P=0.007). MYBL2 was found to be positively correlated with Ki67 (γ=0.286, P=0.003). Furthermore, Kaplan–Meier curves indicated that MYBL2 expression in ESCC tissue was associated with poor patient outcome (P<0.001), with MYBL2-positive patients who exhibited high Ki67 expression in ESCC tissue showing the worst prognosis for overall survival (P=0.003). Our in vitro results showed that downregulation of MYBL2 in ESCC cell lines inhibited cell proliferation and DNA replication (P<0.05 for both). We also found that loss of MYBL2 caused a reduction in levels of cell cycle-related G2/M proteins CDK1 and cyclin B1 in ESCC cells. In contrast, overexpression of MYBL2 caused an increase in these proteins. In vivo, we found that in nude mice that received cells knocked down for MYBL2, tumor growth was inhibited in comparison to the group that received control cells (P<0.05). MYBL2 overexpression induces tumor proliferation in ESCC cells by regulating cell-cycle at the S and G2/M phase. Therefore, MYBL2 may serve as a novel prognostic biomarker in ESCC patients.
OncoTargets and Therapy, Volume 12, pp 1929-1936; doi:10.2147/OTT.S194463
Abstract:Poor prognosis of gastric cancer (GC) has partly been a result of late diagnosis due to nonspecific symptoms in the early stages. The overall survival rate of patients with GC is quite low. Here, we presented the functional role and potential mechanism of long noncoding RNA STXBP5-AS1 in GC. CCK-8, scratch wound healing and Transwell assays were conducted to analyze proliferation, migration, and invasion of SGC7901 and MKN45 cells. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to investigate the relationship between STXBP5-AS1 and STXBP5. Finally, the correlation between STXBP5-AS1 and phosphorylated AKT1 (p-AKT1) was explored to reveal the potential mechanism of STXBP5-AS1 in GC. Western blot assays were performed to analyze phosphorylated AKT1 (p-AKT1) and AKT levels. Our results suggested that STXBP5-AS1 suppressed proliferation, migration, and invasion, and the upregulation of STXBP5-AS1 significantly repressed STXBP5 expression, and knockdown of STXBP5-AS1 promoted STXBP5 expression. In addition, the p-AKT1 level decreased when STXBP5-AS1 was overexpressed and the p-AKT1 level increased with STXBP5-AS1 knockdown in SGC7901 and MKN45 cells. In summary, our results indicate that STXBP5-AS1 inhibits cell proliferation, migration, and invasion through PI3K/AKT in GC.