Cancer Biomarkers - Volume 24, issue 1

Authors: Mo, Ha Yoon | Jo, Yun Sol | Yoo, Nam Jin | Kim, Min Sung | Song, Sang Yong | Lee, Sug Hyung

Article Type: Research Article

Abstract: BACKGROUND: Both QKI and TMEFF2 genes are considered putative tumor suppressor genes (TSGs). In gastric (GC) and colorectal (CRC) cancers, downregulation of their expressions is known to be frequent. However, QKI and TMEFF2 mutations that could potentially inactivate their functions are not reported in cancers. METHODS: In a genome database, we observed that both QKI and TMEFF2 harbor mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we studied 79 GCs and 124 CRCs for the mutations and their intratumoral heterogeneity (ITH). RESULTS: Six of 34 GCs …(17.6%) and 10 of 79 CRCs (12.7%) with MSI-H exhibited QKI frameshift mutations while five of 79 CRCs (6.3%) with high MSI (MSI-H) exhibited TMEFF2 frameshift mutations. However, we found no such mutation in microsatellite stable/low MSI (MSS/MSI-L) cancers within the mononucleotide repeats. We also studied ITH for the detected frameshift mutations in 16 cases of CRCs and detected that QKI and TMEFF2 frameshift mutations showed regional ITH in 2 (12.5%) and 1 (6.3%) cases, respectively. CONCLUSIONS: Our data show that candidate TSG genes QKI and TMEFF2 harbor mutational ITH as well as the frameshift mutations in GC and CRC with MSI-H. From this observation, frameshift mutations of QKI and TMEFF2 may play a role in tumorigenesis through their TSG inactivation in GC and CRC. Show more

Keywords: QK1, TMEFF2, tumor suppressor gene, methylation, frameshift mutation, cancer, microsatellite instability

DOI: 10.3233/CBM-160559

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 1-6, 2019

Authors: Zhang, Nan | Cong, Xiaoqiang | Zhou, Dan | Guo, Liang | Yuan, Congwang | Xu, Dahai | Su, Chang

Article Type: Research Article

Abstract: BACKGROUND: The significance of serum dipeptidyl peptidase-IV (DPP-IV) in papillary thyroid carcinoma (PTC) has not been elucidated. OBJECTIVE: This study aimed to assess the role of serum DPP-IV in the carcinogenesis and prognosis of PTC. METHODS: The serum DPP-IV concentration was measured in 171 male patients with PTC, 81 male patients with a benign thyroid nodule (BTN), and 52 male healthy controls (HCs). Multivariate logistic regression and Cox regression analyses were performed to evaluate the correlations between variables. Receiver operating characteristic (ROC) curves were used to calculate the diagnosis accuracy. RESULTS: …The ROC curve indicated a good performance of DPP-IV for discriminating PTC from BTN, with an area under the curve (AUC) of 0.881 (95% CI, 0.840–0.922). Serum DPP-IV demonstrated a modest performance in predicting nonstructurally persistent disease/recurrent disease (NSPRD) survival, with an AUC of 0.778 (95% CI, 0.635–0.922). A serum DPP-IV level ⩾ 250 nkat/L (HR, 6.529; 95% CI, 2.090–20.398; P = 0.001) and an advanced tumor, lymph node, metastasis (TNM) stage (HR, 4.677; 95% CI, 1.498–14.605; P = 0.008) were found to be independent factors for predicting SPRD. PTC patients with a DPP-IV level ⩾ 250 nkat/L had a worse outcome than those with a DPP-IV level < 250 nkat/L (P < 0.001). CONCLUSIONS: Serum DPP-IV may be a predictive biomarker for PTC diagnosis and prognosis in Chinese male patients. Show more

Keywords: Dipeptidyl peptidase-IV, CD26, papillary thyroid carcinoma, structurally persistent, recurrent disease

DOI: 10.3233/CBM-170908

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 7-17, 2019

Authors: Ries, Jutta | Baran, Christoph | Wehrhan, Falk | Weber, Manuel | Motel, Constantin | Kesting, Marco | Nkenke, Emeka

Article Type: Research Article

Abstract: BACKGROUND: Altered expressions of miR-186, miR-494 and miR-3651 in whole blood of OSCC patients have already been demonstrated. However, nothing is known about their expression in tumor tissues. This study aimed at evaluating differences in miRNA expression in OSCC tissues compared to healthy oral mucosa and at checking if the altered expression is reflected in corresponding blood. METHODS: In 53 OSCC and 40 healthy mucosal tissues the expression of miR-186, -494 and -3651 was determined by RT-qPCR and expression levels were compared between the groups. The altered expression in tissues was compared with that determined for …corresponding blood. MiR-3651 target genes were identified using TargetScan software. RESULTS: Differential expression of miR-186 and miR-494 could not be observed in tumor tissues compared to normal mucosa (p miR-186 = 0.13; p miR-494 = 0.35). Contrary to the detected upregulation of the miR-3651 in the blood of OSCC patients, a significant downregulation was observed in OSCC tissues. A significant correlation between underexpression and diagnosis was ascertained (p = 0.0001). 1710 possible target genes of miR-3651 were identified. CONCLUSIONS: Decreased expression of miR-3651 in OSCC tissues may be a diagnostic biomarker. The opposite change in expression level in the blood might indicate different functions of this miRNA in circulation and tissue. Show more

Keywords: Oral squamous cell carcinoma, whole peripheral blood, tumor tissue, miRNA expression, RT-qPCR

DOI: 10.3233/CBM-180032

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 19-30, 2019

Authors: Zhang, Li-Ya | Chen, Yuan | Jia, Jue | Zhu, Xi | He, Yan | Wu, Li-Ming

Article Type: Research Article

Abstract: BACKGROUND: Ovarian cancer (OC) is the fifth most common type of cancer in women worldwide. MiR-27a plays an important role in the development of ovarian cancer. However, the exact function and molecular mechanism of miR-27a in epithelial-mesenchymal transition (EMT) has not been thoroughly elucidated to date. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of miR-27a and FOXO1 mRNA in ovarian tissues and cells. The function of miR-27a in ovarian cancer was investigated through overexpression and knockdown of miR-27a in vitro. Wound healing and Transwell assays were performed to evaluate the migration and …invasive capacity of the cells. A luciferase reporter assay was conducted to confirm the interaction between miR-27a and FOXO1. Western blotting was used to evaluate FOXO1, EMT and Wnt/β -catenin relative protein expression. RESULTS: In our study, we found that the mRNA expression level of miR-27a was significantly higher in ovarian cancer tissues and in HO8910 and OV90 cells. Functional experiments showed that miR-27a overexpression potentiated the migration and invasion of HO8910 and OV90 cells, while miR-27a inhibition reduced the cells’ migration and invasion. Moreover, miR-27a upregulated the expression of mesenchymal cell markers and downregulated the expression of epithelial cell markers, which were restored via silencing of miR-27a expression. Subsequently, miR-27a was found to directly target and suppress the expression of FOXO1. Finally, we demonstrated that miR-27a promoted the progression of ovarian cancer cells and induced the process of EMT via the Wnt/β -catenin signalling pathway through inhibition of FOXO1. CONCLUSIONS: Taken together, these results indicate that targeting miR-27a and FOXO1 could represent a strategy for anticancer therapy in ovarian cancer. Show more

Keywords: Ovarian cancer, microRNA-27a, FOXO1, EMT, Wnt/β-catenin

DOI: 10.3233/CBM-181229

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 31-42, 2019

Authors: Zhang, Huiping | Wang, Jianfeng | Wang, Zhanying | Ruan, Cailian | Wang, Lu | Guo, Hongtao

Article Type: Research Article

Abstract: BACKGROUND: It is well known that some circulating microRNAs (miRNAs) are highly stable and might serve as promising biomarkers for many types of human cancer including glioblastoma (GBM). However, the potential clinical significance of serum miR-100 in GBM remained unknown. OBJECTIVE: We aimed to detect the expression level of serum miR-100 in patients with GBM and assess its potential diagnostic and prognostic value. METHODS: Quantitative real-time PCR was performed to measure serum miR-100 levels in 95 GBM patients and 60 healthy volunteers. The association between serum miR-100 level and clinicopathological parameters as well …survival of GBM patients was evaluated. RESULTS: Our results revealed that serum miR-100 levels were significantly decreased in GBM patients compared with the healthy controls. Additionally, miR-100 levels were significantly elevated after treatment. Low miR-100 expression was closely correlated with worse clinicopathological characteristics. Further receiver operating characteristic (ROC) curve analysis showed that serum miR-100 could effectively discriminate GBM cases from normal controls. Moreover, survival analyses revealed that patients with high serum miR-100 levels had significantly longer survival time than those with low serum miR-100 levels. Finally, multivariate analysis identified serum miR-100 as an independent prognostic indicator for GBM. CONCLUSIONS: Our findings suggested that serum miR-100 might serve as promising biomarker for GBM diagnosis and prognosis. Show more

Keywords: Glioblastoma, serum miR-100, prognosis, biomarker

DOI: 10.3233/CBM-181416

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 43-49, 2019

Authors: Li, Hong | Wang, Huogang | Deng, Ke | Han, Wei | Hong, Bo | Lin, Wenchu

Article Type: Short Communication

Abstract: BACKGROUND: Cisplatin-based chemotherapy and radiotherapy are the most commonly used treatments for small cell lung cancer (SCLC). However, despise initially dramatic response, the response duration of SCLC patients is variable and resistance to chemo- and radio-therapy inevitably develops. OBJECTIVE: The aim of the study is to investigate the role of Bcl-2 family proteins in predicting SCLC sensitivity to cisplatin treatment, and to identify the potential sensitizer of cisplatin or ratiation treatment in SCLC. METHODS: We collected cisplatin sensitivity data from public available database, and evaluated its possible association with mRNA or protein expression …of Bcl-2 family members in SCLC cell lines. RESULTS: The IC 50 value of cisplatin was significantly correlated with the ratio of Bcl-2/Bim mRNA expression in 33 SCLC cell lines (P = 0.041) as well as the ratio of Bcl-2/Bim protein expression in 7 SCLC cell lines (P = 0.0252). Furthermore, a BH3-mimetic ABT-263 was found to be able to sensitize SCLC cells to cisplatin or radiation. The synergistic and additive antitumor activity of ABT-263 combined with cisplatin or radiation was associated with the enhanced apoptosis, which may be caused by the disruption of Bcl-2 binding to Bim by ABT-263. CONCLUSIONS: Our study indicates that the ratio of Bcl-2/Bim could be a SCLC response predictor to cisplatin, and ABT-263 addition could be an effective strategy to improve the activity of chemo- or radio-therapy in SCLC. Show more

Keywords: Small cell lung cancer, Bcl-2, Bim, ABT-263, cisplatin, radiation

DOI: 10.3233/CBM-181692

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 51-59, 2019

Authors: Wu, Yibin | Fang, Guojiu | Wang, Xin | Wang, Huipeng | Chen, Wenjie | Li, Liang | Ye, Tao | Gong, Lifeng | Ke, Chongwei | Cai, Yuankun

Article Type: Research Article

Abstract: BACKGROUND : Nucleoporin NUP153 (NUP153) is well known to be involved in the regulating of nuclear transport. Although NUP153 is associated with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. OBJECTIVE: The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation. METHODS: The expression levels of NUP153 in CRC tissues and matched normal colon tissues were examined by real-time quantitative PCR and immunohistochemistry. Then the association between NUP153 levels with clinical variables as well …as survival time was investigated. Moreover, overexpression of NUP153 in HCT116 cells was established to study its influence on cell proliferation in vitro , and a xenograft model was performed to explore this effect in vivo . RESULTS: We found that NUP153 was highly expressed in adjacent normal tissues than in cancer tissues, and elevated NUP153 expression was negatively associated with pathological grade (P = 0.015), T stage (P = 0.048) and distant metastasis (P = 0.006). Kaplan-Meier analysis revealed that patients with higher NUP153 expression had a longer overall survival (OS) (P = 0.01) and recurrence free disease (RFS) (P = 0.001). Logistic regression analysis further identified NUP153 as an independent prognostic safe factor for OS and recurrence. Moreover, NUP153 overexpression suppressed CRC cells proliferation and inhibited tumor growth in a xenograft model. Its mechanistic investigations showed that NUP153 overexpression inhibited β -catenin transcriptional activity and down-regulated the mRNA expression levels of Wnt downstream proteins-Axin2, cyclinD1, c-myc and lef-1. CONCLUSIONS: NUP153 might be a promising prognostic factor, a potential tumor suppressor and therapeutic target in human CRC through an interaction with the Wnt/β -catenin signaling pathway. Show more

Keywords: NUP153, colorectal cancer, suppressor gene, prognosis, proliferation, Wnt/β-catenin pathway

DOI: 10.3233/CBM-181703

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 61-70, 2019

Authors: Reyes, Ismael | Reyes, Niradiz | Suriano, Robert | Iacob, Codrin | Suslina, Nina | Policastro, Anthony | Moscatello, Augustine | Schantz, Stimson | Tiwari, Raj K. | Geliebter, Jan

Article Type: Research Article

Abstract: BACKGROUND: Thyroid cancer is the most common endocrine malignancy worldwide, with the predominant form papillary thyroid carcinoma (PTC) representing approximately 80% of cases. OBJECTIVE: This study was addressed to identify potential genes and pathways involved in the pathogenesis of PTC and potential novel biomarkers for this disease. METHODS: Gene expression profiling was carried out by DNA microarray technology. Validation of microarray data by qRT-PCR, western blot, and enzyme linked immunosorbent assay was also performed in a selected set of genes and gene products, with the potential to be used as diagnostic or prognostic …biomarkers, such as those associated with cell adhesion, extracellular matrix (ECM) remodeling and immune/inflammatory response. RESULTS: In this study we found that upregulation of extracellular activities, such as proteoglycans, ECM-receptor interaction, and cell adhesion molecules, were the most prominent feature of PTC. Significantly over-expressed genes included SDC1 (syndecan 1), SDC4 (syndecan 4), KLK7 (kallikrein-related peptidase 7), KLK10 (kallikrein-related peptidase 10), SLPI (secretory leukocyte peptidase inhibitor), GDF15 (growth/differentiation factor-15), ALOX5 (arachidonate 5-lipoxygenase), SFRP2 (secreted Frizzled-related protein 2), among others. Further, elevated KLK10 levels were detected in patients with PTC. Many of these genes belong to KEGG pathway “Proteoglycans in cancer”. CONCLUSIONS: Using DNA microarray analysis allowed the identification of genes and pathways with known important roles in malignant transformation, and also the discovery of novel genes that may be potential biomarkers for PTC. Show more

Keywords: Biological Markers, gene expression, kallikrein-related peptidase, thyroid carcinoma

DOI: 10.3233/CBM-181758

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 71-83, 2019

Authors: Ma, Baofeng | Liu, Xiaoming | Yu, Zhaoxiao

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the effects of high intensity focused ultrasound on liver function, tumor markers and survival rate of hepatocellular carcinoma patients. METHODS : Ninety six cases with primary liver cancer patients, consisting of 66 males and 30 females, were enrolled in this study and treated with high intensity focused ultrasound combined with stereotactic segmentation dose radiation, low frequency for 10 times, followed by analysis of KPS score of liver cancer, Child-Pugh, grading and staging of liver cancer, 3 months, 6 months, 1 year of clinical symptom remission rate, tumor markers, liver function, survival rate, as well as the change of immune related …cytokines. RESULTS: Three months after high intensity focused ultrasound treatment, abdominal distension abdominal pain, jaundice symptoms, anorexia and ascites were significantly relieved compared with before treatment (P < 0.05). At 3 months after treatment, levels of AFP and CA199 were significantly reduced than before treatment (P < 0.05). Meanwhile, Child-Pugh classification score was significantly decreased at 3 months after treatment compared with before treatment, which was further decreased at 6 months after treatment than 3 months after treatment (P < 0.05). In addition, ALT, AST, AKP, propagated and TBIL level at 3 months after treatment displayed no differences to those before treatment but was significantly decreased at 6 months treatment (P < 0.05). Moreover, the late stages of liver cancer, the lower survival rate after treatment. Furthermore, the levels of NK, CD3, CD4, CD8 and CD4/CD8 cytokines were significantly increased at 3 months after treatment (P < 0.05), together with significantly increased levels of IFN-r and IL-2 and decreased levels of IL-4 and IL-10 (P < 0.05). CONCLUSION: High intensity focused ultrasound can effectively improve liver function, increase the survival rate and enhance immune function of patients with liver cancer. Show more

Keywords: Ultrasonic treatment, liver cancer, curative effect, immunizing

DOI: 10.3233/CBM-181822

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 85-90, 2019

Authors: Nomura, Megumi | Matsumoto, Kazumasa | Shimizu, Yuriko | Ikeda, Masaomi | Amano, Noriyuki | Nishi, Mayuko | Ryo, Akihide | Nagashio, Ryo | Sato, Yuichi | Iwamura, Masatsugu

Article Type: Research Article

Abstract: BACKGROUND: New biomarkers may help us provide individualized prognosis and allow risk-stratified clinical decision making about radical treatment. OBJECTIVES: This study aimed to determine the tumor necrosis factor of receptor superfamily 19 (TROY) expression in urothelial carcinoma and its relationship to clinicopathological findings. METHODS: Immunohistochemical staining for TROY was carried out in 136 archival radical cystectomy specimens with immunoreactivity being stratified on a 0–9 scale. Expression scores for TROY were further stratified into negative (score 0) and positive (score 1 or greater). Median age was 65 years, and the median follow-up period was …50.7 months. RESULTS: Expression of TROY was significantly associated with the pathological stage (p = 0.019) and expression of nestin (p = 0.013). Log-rank tests indicated that expression of TROY was significantly associated with disease progression and cancer-specific mortality (p = 0.044 and 0.008, respectively). In multivariate Cox regression analysis, lymph node status was the only independent prognostic factor for disease progression and cancer-specific survival. Expression of TROY was a marginal prognostic factor for cancer-specific survival. CONCLUSIONS: TROY may therefore be a new molecular marker to aid in identifying and selecting patients undergoing radical cystectomy who could potentially benefit from multimodal treatment. Show more

Keywords: Bladder cancer, cystectomy, nestin, urothelial carcinoma, TROY

DOI: 10.3233/CBM-181911

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 91-96, 2019

Authors: Huang, Chaoping | Li, Yan | Zhao, Wei | Zhang, Aobo | Lu, Cheng | Wang, Zhenxiao | Liu, Liangfa

Article Type: Research Article

Abstract: Cancer stem cells (CSCs) have the ability to dictate tumor initiation, recurrence, and metastasis. Here, we examined the expression of aα 2δ 1 + in laryngeal cancer tissues and further determined the effect of α 2δ 1 on the migratory ability and tumorigenicity of laryngeal cancer cells. Immunofluorescence staining revealed that α 2δ 1 was positive in 13 (13/16, 81.25%) cases in laryngeal squamous cell carcinoma (LSCC) tissues, 7 (7/16, 43.75%) cases in paracancerous tissues and only 2 (2/16, 12.5%) cases in normal tumor …tissues. Our quantitative RT-PCR assays further showed that α 2δ 1 + LSCC cells expressed significantly higher levels of stem cell-associated genes and drug efflux and resistance genes versus α 2δ 1 - cells. Sphere-forming assays demonstrated higher sphere-forming efficiency in the α 2δ 1 + versus α 2δ 1 - subpopulation. Our Matrigel assays showed that α 2δ 1 + cells exhibited significantly greater invasive and migratory ability than α 2δ 1 - cells. Furthermore, the percentage of purified α 2δ 1 + in TU686 and TU212 cells treated cisplatin or paclitaxel was significantly higher than that of the control group. Tumor xenograft assays revealed that the tumorigenicity of α 2δ 1 + cells was much higher than α 2δ 1 - cells. In conclusion, a α 2δ 1 + subpopulation with CSC-like property was present in laryngeal cancer and possessed high self-renewal activity and was sufficient for tumor growth, differentiation, migration, invasion, and chemotherapeutic resistance. They could represent a promising therapeutic target for LSCC. Show more

Keywords: Laryngeal squamous cell carcinoma, cancer stem cells, α2δ1

DOI: 10.3233/CBM-181947

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 97-107, 2019

Authors: Luo, Junfeng | Lou, Zhengda | Zheng, Junzheng

Article Type: Research Article

Abstract: Bladder cancer is frequently occurred in urinary system and has complicated pathogenesis factors including both genetics and environmental factors that have not been fully illustrated. Hypoxia can further induce tumor progression. ROCK2 has abnormal expression in various tumors but its expression or functional role in bladder cancer have not been illustrated. In vitro cultured bladder cancer cell line T24 was randomly assigned into control group, hypoxia group (prepared under hypoxic culture), and ROCK2 siRNA group (transfected with ROCK2 siRNA after hypoxia treatment). Real-time PCR and Western bot measured ROCK2 expression. MTT assay tested cell proliferation, and cell migration was …quantified. Cell apoptosis was measured by caspase3 activity assay kit and Transwell chamber measured cell migration. Western blot quantified expressional change of HIF-1α and E-cadherin, and Wnt signal pathway proteins including Wnt4, and β -catenin. ROCK2 is up-regulated in bladder cancer T24 cells under hypoxia, and can facilitate cell proliferation, migration and invasion, inhibited Caspase3 activity, enhanced HIF-1α expression, decreased E-cadherin expression, and up-regulated Wnt4 and β -catenin (p < 0.05 comparing to hypoxia group). Under hypoxia conditions, ROCK2 can facilitate apoptosis of bladder cancer cells via modulating Wnt signal pathway, inhibit cell proliferation, migration, invasion or formation of epithelial mesenchymal transition (EMT). Show more

Keywords: ROCK2, bladder cancer, Wnt signal pathway, hypoxia, HIF-1α, cell proliferation

DOI: 10.3233/CBM-181949

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 109-116, 2019

Authors: Moschovis, D. | Vasilaki, E. | Tzouvala, M. | Karamanolis, G. | Katifelis, H. | Legaki, E. | Vezakis, A. | Aravantinos, G. | Gazouli, M.

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression. OBJECTIVE: The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility. METHODS: A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a …population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls). RESULTS: Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients. CONCLUSIONS: Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results. Show more

Keywords: Long non-coding RNA, polymorphisms, pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors

DOI: 10.3233/CBM-181959

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 117-123, 2019

Authors: Su, Hailong | Wang, Xuebo | Song, Jingjing | Wang, Yongjiao | Zhao, Yingchun | Meng, Juan

Article Type: Research Article

Abstract: BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms’ Tumor (WT). METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a …dual luciferase assay in SK-NEP-1 cells. RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro , overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT. CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3. Show more

Keywords: Wilms Tumor, miR-539, JAG1, Notch 1, Notch 3

DOI: 10.3233/CBM-181972

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 125-133, 2019

Authors: Surov, Alexey | Meyer, Hans Jonas | Höhn, Anne-Kathrin | Schob, Stefan | Winter, Karsten | Sabri, Osama | Purz, Sandra

Article Type: Research Article

Abstract: BACKGROUND: The aim of our study was to investigate possible relationships between 18 F-FDG-PET parameters and clinically relevant histopathological findings in patients with cervical cancer (CC). METHODS: Eighteen female patients (mean age 55.4 years) with histologically confirmed squamous cell CC were involved into the study. In all cases, 18 F-FDG-PET CT was performed. Mean and maximum standardized uptake values (SUV mean and SUV max ), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were determined on PET-images. For every tumor …the following specimen stainings were performed: epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α , and histone 3. All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman’s correlation coefficient (p ) was used to analyze associations between investigated parameters. p -values < 0.05 were taken to indicate statistical significance. RESULTS: TLG and MTV correlated well with expression of EGFR (p = 0.601, P = 0.008 and p = 0.586, P = 0.011, respectively). SUV median correlated inversely with expression of HIF 1alpha (p = - 0.509, P = 0.031). SUV mean tended to correlate with expression of EGFR and HIF 1alpha. None of the PET parameters correlated with expression of Histone 3, p53 and VEGF. CONCLUSION: TLG and MTV can reflect expression of EGFR and SUV median correlated significantly with expression of HIF-1α . None of the PET parameters can predict expression of Histone 3, p53 and VEGF. Show more

Keywords: Uterine cervical cancer, 18F-FDG-PET, EGFR, VEGF, p53, HIF 1alpha, p53

DOI: 10.3233/CBM-182019

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 135-140, 2019