Cancer Biomarkers - Volume 21, issue 4

Authors: Saeednejad Zanjani, Leili | Madjd, Zahra | Abolhasani, Maryam | Shariftabrizi, Ahmad | Rasti, Arezoo | Asgari, Mojgan

Article Type: Research Article

Abstract: BACKGROUND: CD105 is recently described as a cancer stem cell (CSC) marker. OBJECTIVE: The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). METHODS: Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. RESULTS: In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly …associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. CONCLUSIONS: We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes. Show more

Keywords: CD105, renal cell carcinoma (RCC), cancer stem cells (CSCs), endothelial expression, tissue microarray (TMA), RCC subtypes

DOI: 10.3233/CBM-170755

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 821-837, 2018

Authors: Weiten, Richard | Müller, Tim | Schmidt, Doris | Steiner, Susanne | Kristiansen, Glen | Müller, Stefan C. | Ellinger, Jörg | Syring, Isabella

Article Type: Research Article

Abstract: BACKGROUND/OBJECTIVE: MED15 is a part of the multiprotein Mediator complex which is involved in the transcription of polymerase (Pol) II-dependent genes. Several studies in this field have reported altered expressions of distinct subunits in human malignancy. However, the role of MED15 in renal cell carcinoma (RCC) has not be investigated yet. METHODS: First, we performed an RNA expression and survival analysis of MED15 in RCC by using the database cBioPortal. To confirm these data on the protein level, we executed immunohistochemical (IHC) staining against MED15 on a tissue microarray containing 184 samples of the most common …subtypes of the tumour at the various stages. Further, we performed functional analysis including proliferation, migration, and invasion assays on the RCC cell lines A-498 and ACHN following the siRNA-mediated MED15 knockdown. RESULTS: On the mRNA level, higher expression of MED15 was associated with worse patient survival rates. IHC staining validated this tendency, unfortunately the results were not significant. However, supporting this tendency, in vitro -assays showed a significant decrease in proliferation, migration, and invasion after knockdown of MED15 . CONCLUSION: The research concludes that MED15 does seem to play a tumour promoting role in the progression and metastatic spread of renal cell carcinoma. Show more

Keywords: Mediator complex, renal cell carcinoma, MED15, tumour promoter

DOI: 10.3233/CBM-170757

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 839-847, 2018

Authors: Xue, Jinfang | Liao, Liya | Yin, Fang | Kuang, Haoyu | Zhou, Xiaojun | Wang, Yanan

Article Type: Research Article

Abstract: BACKGROUND: LncRNAs are involved in the metastasis and recurrence of human tumors, including colorectal cancer (CRC). We previously reported that lncRNA AB073614 promotes tumor proliferation and metastasis and predicted a poor clinical outcome of CRC patients. Herein, we investigated the underlying mechanism of lncRNA AB073614-related metastasis in CRC. MATERIAL AND METHODS: The expression of lncRNA AB073614 in CRC tissues were evaluated by quantitative real-time PCR (qRT-PCR). Transwell assay was performed to detect the effects of lncRNA AB073614 on cell migration and invasion. Epithelial-mesenchymal transition (EMT) molecular markers and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) …pathway proteins expression levels were detected by Western blot and Immunofluorescence. RESULTS: We confirmed that lncRNA AB073614 was highly expressed in the colorectal cancer tissues. LncRNA AB073614 knockdown in SW480 and HCT116 cells significantly promoted the protein expression levels of E-cadherin and Occludin, and decreased the expressions of N-cadherin and Vimentin, then further decreased the cell migration and invasion ability. Interestingly, the expression of phosphorylated STAT3 was also down-regulated. Furthermore, SW480 and HCT116 cells were transfected with lncRNA AB073614 vector and treated with a JAK inhibitor, AT9283. The results showed that lncRNA AB073614 regulated EMT through JAK-STAT3 signaling pathway. CONCLUSION: All these results indicate that lncRNA AB073614 can induce the expression of EMT cell markers and regulate the process of EMT of CRC cells through regulating the JAK/STAT3 pathway activation. Show more

Keywords: Colorectal cancer, LncRNA AB073614, JAK/STAT3, epithelial-mesenchymal transition

DOI: 10.3233/CBM-170780

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 849-858, 2018

Authors: Zhao, Xianguang | Chen, Yang | Mao, Qiqi | Jiang, Xiaoyun | Jiang, Weiru | Chen, Jiajie | Xu, Weijia | Zhong, Liang | Sun, Xu

Article Type: Research Article

Abstract: In China, hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer death in men, followed by lung and stomach cancer. There was an urgent need to identify novel prognostic biomarkers for HCC. We explored the expression pattern of m6A related proteins in HCC tissues by using TCGA in this study. We found that the m6A ‘reader’ YTHDF1 was significantly upregulated in HCC and was positive correlated with pathology stage. Kaplan-Meier analysis showed that Lower YTHDF1 expression level was associated with better survival of HCC patients. Furthermore, we performed GO and KEGG pathway analysis of …YTHDF1 co-expressed genes and found YTHDF1 played an important role in regulating HCC cell cycle progression and metabolism. We believed that this study will provide a potential new therapeutic and prognostic target for HCC. Show more

Keywords: YTHDF1, HCC, m6A, prognostic, biomarker

DOI: 10.3233/CBM-170791

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 859-868, 2018

Authors: Vocka, Michal | Langer, Daniel | Fryba, Vladimir | Petrtyl, Jaromir | Hanus, Tomas | Kalousova, Marta | Zima, Tomas | Petruzelka, Lubos

Article Type: Research Article

Abstract: BACKGROUND: GDF-15 is a protein belonging to the transforming growth factor beta superfamily that has a role in regulating inflammatory and apoptotic pathways. High level GDF-15 in tumor tissues and plasma correlate with an increased risk of recurrence and reduced overall survival. OBJECTIVE: The aim of this study was to screen GDF-15 capacity to detecting metastatic CRC and compare it with standard tumor markers CEA and CA19-9. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of GDF-15, CEA and CA19-9 were measured …by immunochemically. A Kaplan-Meier curve was applied for analysis of survival rates, and a log-rank was used for univariate analysis. RESULTS: Serum levels of GDF-15 were significantly higher in patients with colorectal cancer compared to healthy controls (p < 0.001). In addition, serum levels of GDF-15 correlated with extent of liver involvement and patients with higher GDF-15 levels had significantly worse outcome (p < 0.0001). CONCLUSIONS: Our results show GDF-15 as an effective biomarker in patients with metastatic colorectal cancer with the same sensitivity as CEA. In addition, GDF-15 levels strongly correlate with extension of liver involvement in contrast with CEA. Show more

Keywords: GDF-15, colorectal cancer, biomarker, survival

DOI: 10.3233/CBM-170792

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 869-874, 2018

Authors: Wang, Dong | Zhou, Juan | Zheng, Jihua | Zhang, Jiang | Chen, Yaoming | Li, Wen | Wang, Ruizhi

Article Type: Research Article

Abstract: BACKGROUND: Cisplatin-based concurrent chemoradiotherapy is recommended for nasopharyngeal carcinoma (NPC) at advanced stages. Excision repair cross-complementation group 1 (ERCC1) plays an important function in the repair of DNA damage that is a critical process of chemo- and radiotherapy. OBJECTIVE: This study aimed to investigate the clinical significance of ERCC1 expression in NPC treated with cisplatin-based concurrent chemoradiotherapy in locoregionally advanced NPC. METHODS: The expression level of ERCC1 and its association with clinicopathological characteristics in 205 locoregionally advanced NPC patients receiving cisplatin-based concurrent chemoradiotherapy were analyzed retrospectively. RESULTS: The correlation analysis …revealed that the treatment-sensitive patients displayed dramatically lower ERCC1 expression than treatment-resistant cases did. Furthermore, the Kaplan-Meier plots revealed lower ERCC1 expression was significantly associated with better survival. Multivariate analysis further showed that the ERCC1 expression was an independent predictor of NPC patients’ survival. CONCLUSIONS: ERCC1 expression might be a useful predictive marker in patients with locoregionally advanced NPC receiving cisplatin-based concurrent chemoradiotherapy. Show more

Keywords: ERCC1, cisplatin-based concurrent chemoradiotherapy, nasopharyngeal cancer, survival

DOI: 10.3233/CBM-170817

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 875-881, 2018

Authors: Hu, Jianxia | Liu, Xiaoyi | Chi, Jingwei | Che, Kui | Feng, Yan | Zhao, Shihua | Wang, Zhongchao | Wang, Yangang

Article Type: Research Article

Abstract: BACKGROUND: Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. OBJECTIVE: To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. METHODS: We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. RESULTS: The expression levels …of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (P < 0.01). The expression levels of IGF-1 and ERK in MS patients with CRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (P < 0.01). Expression levels of ERK, IGF-1, GLUT4 were associated with clinical characteristics of CRC, including tumor size, distant metastasis and advanced stages (III/IV) (P < 0.05). CONCLUSIONS: Expressions of IGF-1, ERK and GLUT4 in greater omental adipose tissues might be useful biomarkers and predictive targets in the diagnosis of CRC. Show more

Keywords: Metabolic syndrome, colorectal cancer, IGF-1, ERK, GLUT4

DOI: 10.3233/CBM-170942

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 883-891, 2018

Authors: Qiu, Fei | Gao, Wei | Wang, Bin

Article Type: Research Article

Abstract: Colorectal cancer (CRC) is one of the most common malignant tumors in digestive tract. Previous study found close correlation between insulin-like growth factor binding proteins (IGFBPs) and occurrence of multiple tumors. This study aims to analyze the effects of IGFBP6 on the apoptosis and migration of tumor cells, and to investigate underlying mechanism. HCT-116 or SW480 cell was cultured with 1.0 mg/l, 10 mg/l and 100 mg/l IGFBP-6. MTT assay was employed to test the proliferation activity of tumor cells after differential treatment. The cell cycle of tumor cells was detected by flow cytometry, while Transwell assay was used to quantify the invasion …and migration of tumor cells after IGFBP-6 intervention. In experimental group with IGFPB-6 application, the proliferation rate of HCG-116 or SW480 cells was gradually decreased with higher concentrations of IGFBP-6 (p < 0.05). The ratio of cells at G0/G1 phase was increased while S phase and G2/M phase ratio were all decreased with IGFPB-6. With further elevated concentration of IGFPB-6, there was more potency of higher G0/G1 ratio and lower S phase or G2/M phase (p < 0.05). Both invasion and migration ability of HCT-116 or SW480 cells in experimental group were decreased. With elevated IGFBP-6 concentration, cell invasion and migration were further weakened (p < 0.05). IGFBP-6 could inhibit invasion and migration of colorectal carcinoma cells possibly via inhibiting proliferation activity and arresting cell cycle of HCT-116 or SW480 cells. Show more

Keywords: IGFBP-6, colorectal cancer, cell apoptosis, migration

DOI: 10.3233/CBM-170947

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 893-898, 2018

Authors: Yao, Qiang | Wang, Weimin | Jin, Jun | Min, Ke | Yang, Jian | Zhong, Yubing | Xu, Chunni | Deng, Jianliang | Zhou, Yan

Article Type: Research Article

Abstract: BACKGROUND: Expressions of Caspase-8 and Caspase-3 have been identified as important markers in many malignant tumors, but their roles in colorectal cancer (CRC) have not been confirmed. The purpose of this study was to investigate the role of Caspase-8 and Caspase-3 in CRC. METHODS: We enrolled 470 CRC patients in this study. Archival paraffin-embedded CRC tissue samples were used to construct tissue microarray (TMA), expressions of Caspase-8 and Caspase-3 that were stained by immunohistochemistry. Prognostic and predictive role of Caspase-8 and Caspase-3 expressions, alone or united, were evaluated by univariate and multivariate analysis respectively. …RESULTS: In comparison with adjacent normal tissues, Caspase-8 and Caspase-3 protein levels were upregulated in CRC tissues significantly, furthermore, high expressions of Caspase-8 and Caspase-3 were correlated with decreased overall survival (OS) (p < 0.05), and also with unfavorable clinicopathologic characteristics. Cox regression analysis showed that high Caspase-8 and Caspase-3 expressions were independent negative markers of OS. CONCLUSION: Caspase-8 and Caspase-3 expressions in tumor tissues are novel candidate prognostic markers for CRC patients. It was the first time to be identified that Caspase-8 and Caspase-3 expressions had synergistic role as efficient prognostic indicators for CRC patients. Show more

Keywords: Caspase-8, Caspase-3, colorectal cancer (CRC), diagnosis, prognosis

DOI: 10.3233/CBM-170967

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 899-908, 2018

Authors: Cui, Li-Na | Li, Na | Fu, Shuang | Zhang, Xin | Wang, Xin | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Mean platelet volume (MPV) is an indicator of activated platelets. OBJECTIVE: We aimed to investigate whether the combination of D-dimer and MPV could have a better performance in predicting deep venous thrombosis (DVT) in patients with breast cancer. MEHTODS: In 342 consecutive breast cancer patients without preoperative DVT, we measured the preoperative D-dimer and MPV levels. Compression ultrasonography was performed in all breast cancer patients before surgery, as well as one month, three months, six months, and twelve months. …RESULTS: During a median period of twelve months, 15 of the 234 patients (6.4%) developed DVT. MPV was reduced and D-dimer was increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealed that both MPV and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.619 (95% CI: 0.553 to 0.681) when D-dimer was used alone, whereas it increased to 0.790 (95% CI 0.732 to 0.840, p < 0.001) with the addition of MPV. CONCLUSIONS: The combination of preoperative D-Dimer and MPV improves the predictive power of postoperative DVT risk in breast cancer patients. Show more

Keywords: Breast cancer, D-dimer, mean platelet volume, risk prediction

DOI: 10.3233/CBM-170975

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 909-913, 2018

Authors: Liu, Yuan | Men, Changping | Xu, Yingmin | Zhao, Kai | Luo, Lei | Dong, Dahai | Yu, Qinchao

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Clusterin promotes cell proliferation, motility and invasiveness in human renal cell carcinoma (RCC) cells but the underlying molecular mechanisms of this action are largely unknown. The aim of this study was to investigate the effects of clusterin on cancer cell growth, invasion and S100A4 expression and to determine the effects of clusterin on in vitro cell proliferation and migration and in vivo tumour growth in RCC cells. METHODS: We have established stable transfectants of highly invasive Caki-1 human RCC cells with expression of clusterin shRNA targeting clusterin (Caki-1/clusterin shRNA). We also …established stable transfectants of 786-O human RCC cells with expression of clusterin cDNA plaismid (786-O/clusterin cDNA). Clusterin and S100A4 expression was detected by reverse transcription (RT) PCR and western blot assay; Caki-1/clusterin shRNA and 786-O/clusterin cDNA clones were subjected to in vitro -invasion assays. Cell viability and cell growth was assessed in MTT and clonogenic assay. Specific small interfering RNA was employed to down-regulate S100A4. The expression plasmid for S100A4 (pCMV-S100A4) was used to upregulate S100A4. Caki-1/clusterin shRNA clones were injected subcutaneously in nude mice to determine tumour growth and cancer cell invasiveness in vivo . Xenograft tumour tissues were assessed by immunohistochemistry and frozen tissues were used for the detection of S100A4 and clusterin. RESULTS: Overexpression of clusterin increased cell invasiveness; and targeting clusterin reduced cell invasiveness in vitro . This increase in cell invasiveness was mediated by S100A4. Targeting clusterin decreased cell proliferation and down-regulated cellular S100A4 levels in Caki-1 cells; Overexpression of clusterin increased cell proliferation and up-regulated cellular S100A4 levels in 786-O cells; Stable Caki-1/clusterin shRNA transfectants produced smaller xenograft tumours containing reduced S100A4 protein levels in vivo . Stable 786-O/clusterin cDNA transfectants produced larger xenograft tumours containing increased S100A4 protein levels in vivo . CONCLUSION: Our results indicate that clusterin promotes growth and invasion in RCC cells in vitro and in vivo through upregulation of S100A4; And targeting clusterin confers growth inhibitory and anti-invasive properties in RCC cells in vitro and in vivo through a down-regulation of S100A4. These findings provide the rationale for future oncostatic strategies aimed at suppressing clusterin-mediated signal transduction pathways as a novel therapeutic approach in human RCC. Show more

Keywords: Renal cell carcinoma, invasion, growth, clusterin, S100a4

DOI: 10.3233/CBM-171018

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 915-923, 2018

Authors: Zhou, Qianping | Huang, Lanshan | Gu, Yongyao | Lu, Huiping | Feng, Zhenbo

Article Type: Research Article

Abstract: BACKGROUND: Molecular target therapy has become a hot spot in cancer treatment, finding effective targets for diffuse large B cell lymphoma (DLBCL) is an urgent problem. OBJECTIVE: To detect the expression level of C-C motif chemokine ligand 18 (CCL18) in DLBCL and clarify its potential role in the progression of DLBCL. METHODS: Gene expression datas of DLBCL were obtained from TCGA and GEO databases. The relationship between CCL18 and clinicopathologic information of DLBCL was assessed using meta-analysis method. Then we conducted bioinformatics analysis to uncover the biological function of CCL18 and its co-expression …genes. Immunohistochemistry was applied to detect expression of CCL18 in DLBCL and reactive hyperplasia lymphoid tissues. RESULTS: The expression of CCL18 in DLBCL was higher than negative control group. The levels of CCL18 were distinct in different molecular subtypes and ages, and patients with higher level of CCL18 had a shorter overall survival than those with lower level. CCL18 and its co-expression genes were enriched in biological function such as cell proliferation, migration, apoptotic, and correlated with NF-κ B, pathway in cancer, PI3K-AKT pathway. CONCLUSIONS: CCL18 was up-regulated in DLBCL and related to poor prognosis. CCL18 may act as a valuable target for diagnosis and treatment of DLBCL. Show more

Keywords: CCL18, DLBCL, meta-analysis, bioinformatics, immunohistochemistry

DOI: 10.3233/CBM-171097

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 925-934, 2018