Cancer Biomarkers - Volume 21, issue 1

Authors: Sun, Si | Wu, Qi | Song, Junlong | Sun, Shengrong

Article Type: Research Article

Abstract: Besides the crucial role of hyperinsulinemia in the development of breast cancer with Type 2 diabetes mellitus (T2DM), it has been shown that hyperglycemia could contribute to promote cancer progression. A remarkable association within hyperglycemia, PKCδ and Ubiquitin-proteasome system (UPS) has been reported, suggesting that PKCδ may mediate high glucose-induced UPS activation in breast cancer cells. Although the independent effects of PKCδ or UPS on breast cancer and T2DM are increasingly supported by experimental evidence, the complex interactional link between PKCδ and UPS is still unclear. Hence, we …focus on the relationship between PKCδ and UPS in breast cancer with T2DM. We hypothesize that PKCδ may have the function to regulate the activity of UPS. Further, we speculate that PKCδ combine with proteasome α 2 promoter, that indicate PKCδ regulate the function of UPS by change the composition of proteasome. Therefore, we surmise that PKCδ mediated high glucose-induced UPS activation in breast cancer cells, and specific PKCδ inhibitor rottlerin significantly suppressed elevated glucose induced the activity of UPS. We hope that our paper will stimulate further studies the relationship between PKCδ and UPS, and a new targeted therapy and early medical intervention for PKCδ could be a useful option for breast cancer cases complicated with T2DM or hyperglycemia. Show more

Keywords: Protein kinase C δ, Ubiquitin-proteasome system, breast cancer

DOI: 10.3233/CBM-170451

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 1-9, 2018

Authors: Liu, Yanni | Nan, Fangfang | Lu, Kexin | Wang, Yunfang | Liu, Yu | Wei, Shuangyan | Wu, Ruixue | Wang, Ying

Article Type: Research Article

Abstract: BACKGROUND: Understanding the molecular mechanisms is important in development and therapy of endometrioid endometrial adenocarcinoma. OBJECTIVE: To identify key genes in endometrioid endometrial adenocarcinoma. METHODS: The data of mRNA, miRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) database and differential analysis was performed. Then, bioinformatic analysis was used to explore the regulatory mechanisms of miRNA and DNA methylation on gene expression. The regulatory network between differentially expressed miRNAs and target genes was established. Finally, the quantitative RT-PCR was applied to validate the bioinformatics results. RESULTS: We …obtained biological omics data of 381 patients with endometrioid endometrial adenocarcinoma from TCGA data portal. After data processing, up to 2068 DEGs and 69 differentially expressed miRNAs were identified. Prediction and correlation analysis revealed that 175 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. After the integrated analysis of differentially methylated CpG islands and DEGs, 16 related genes were obtained. The quantitative RT-PCR results were roughly consistent with the bioinformatics analysis. CONCLUSIONS: The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1, PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of endometrioid endometrial adenocarcinoma and could be used as potential therapeutic targets for the disease. Show more

Keywords: Differentially expressed genes, DNA methylation, endometrioid endometrial adenocarcinoma, miRNAs

DOI: 10.3233/CBM-170164

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 11-21, 2018

Authors: Chen, Min | Wu, Xiaoliang | Ma, Wenjuan | Zhou, Qianghua | Wang, Xing | Zhang, Rongxin | Wang, Jiahong | Yang, Xianzi

Article Type: Research Article

Abstract: BACKGROUND: A recent study has demonstrated that the long non-coding RNA VPS9D1-AS1 is highly expressed in colorectal cancer and predicts poor prognosis. However, roles of VPS9D1-AS1 in gastric cancer remained poorly understood. OBJECTIVE: The aim of this study is to decipher the expression of VPS9D1-AS1 in gastric cancer (GC) patients, so as to assess whether or not it could be used as a novel biomarker for prognosis in gastric cancer patients. METHODS: The expression of VPS9D1-AS1 was examined in cancer tissues and paired adjacent non-tumorous tissues from 126 gastric cancer patients using qRT-PCR. …Correlations between the expression of VPS9D1-AS1 and clinicopathological parameters and patients’ survival were analyzed. RESULTS: VPS9D1-AS1 expression was downregulated in gastric cancer tissues than that in adjacent non-tumorous tissues (P < 0.001). VPS9D1-AS1 expression level was markedly correlated with tumor size and TNM stage in gastric cancer. Kaplan-Meier analysis showed low expression of VPS9D1-AS1 were correlated with poor overall and disease free survival. On multivariate analysis, the hazard ratio of VPS9D1-AS expression was 0.30 (95% CI = 0.13–0.66, P = 0.003) for overall survival. CONCLUSIONS: Overall, our data suggest that downregulated VPS9D1-AS1 may be used as a novel prognosis predictor of gastric cancer. Show more

Keywords: Long non-coding RNA, VPS9D1-AS1, gastric cancer, downregulation

DOI: 10.3233/CBM-170172

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 23-28, 2018

Authors: Oakley-Girvan, Ingrid | Davis, Sharon Watkins

Article Type: Research Article

Abstract: BACKGROUND: Detecting volatile organic compounds (VOCs) could provide a rapid, noninvasive, and inexpensive screening tool for detecting cancer. OBJECTIVE: In this systematic review, we identified specific exhaled breath VOCs correlated with lung, colorectal, and breast cancer. METHODS: We identified relevant studies published in 2015 and 2016 by searching Pubmed and Web of Science. The protocol for this systematic review was registered in PROSPERO and the PRISMA guidelines were used in reporting. VOCs and performance data were extracted. RESULTS: Three hundred and thirty three records were identified and 43 papers were …included in the review, of which 20 were review articles themselves. We identified 17 studies that listed the VOCs with at least a subset of statistics on detection cutoff levels, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and gradient. CONCLUSIONS: Breath analysis for cancer screening and early detection shows promise, because samples can be collected easily, safely, and frequently. While gas chromatography-mass spectrometry is considered the gold standard for identifying specific VOCs, breath analysis has moved into analyzing patterns of VOCs using a variety of different multiple sensor techniques, such as eNoses and nanomaterials. Further development of VOCs for early cancer detection requires clinical trials with standardized breath sampling methods. Show more

Keywords: Exhaled breath, volatile organic compounds (VOCs), biomarkers, lung cancer, colorectal cancer, breast cancer

DOI: 10.3233/CBM-170177

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 29-39, 2018

Authors: Trojani, Alessandra | Pungolino, Ester | Rossi, Giuseppe | D’Adda, Mariella | Lodola, Milena | Camillo, Barbara Di | Perego, Alessandra | Turrini, Mauro | Orlandi, Ester | Borin, Lorenza | Iurlo, Alessandra | Malato, Simona | Spina, Francesco | Latargia, Maria Luisa | Lanza, Francesco | Artale, Salvatore | Anghilieri, Michela | Carraro, Maria Cristina | Canal, Gabriella De | Morra, Enrica | Cairoli, Roberto

Article Type: Research Article

Abstract: BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions.

DOI: 10.3233/CBM-170209

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 41-53, 2018

Authors: Bao, Xu | Duan, Junyao | Yan, Yongji | Ma, Xin | Zhang, Yu | Wang, Hanfeng | Ni, Dong | Wu, Shengpan | Peng, Cheng | Fan, Yang | Gao, Yu | Li, Xintao | Chen, Jianwen | Du, Qingshan | Zhang, Fan | Zhang, Xu

Article Type: Research Article

Abstract: BACKGROUND: Renal cell carcinoma (RCC) is one of the most malignant genitourinary diseases worldwide. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs in the human genome that are involved in RCC initiation and progression. OBJECTIVE: To investigate the expression of PVT1 in ccRCC and evaluate its correlation with clinicopathologic characteristics and patients’ survival. METHODS: Quantitative real-time PCR was performed to examine PVT1 expression in 129 ccRCC tissue samples and matched adjacent normal tissue samples. The relationship of PVT1 expression with clinicopathologic characteristics and clinical outcome was evaluated. RESULTS: …We identified the lncRNA PVT1, which was upregulated in clear cell renal cell carcinoma (ccRCC) tissues when compared with corresponding controls. Furthermore, PVT1 expression was positively associated with gender, tumor size, pT stage, TNM stage, and Fuhrman grade. Kaplan-Meier survival analysis showed that patients with high PVT1 expression had shorter disease-free survival (DFS) and overall-survival (OS) than those with low PVT1 expression, and multivariate analysis identified PVT1 as an independent prognostic factor in ccRCC. CONCLUSIONS: PVT1 may be an oncogene as well as may promote metastasis in ccRCC and could serve as a potential biomarker to predict the prognosis of ccRCC patients. Show more

Keywords: Long noncoding RNA, PVT1, clear cell renal cell carcinoma, prognosis

DOI: 10.3233/CBM-170251

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 55-63, 2018

Authors: Zhou, Rong-Miao | Li, Yan | Liu, Jiang-Hui | Wang, Na | Huang, Xi | Cao, Shi-Ru | Shan, Bao-En

Article Type: Research Article

Abstract: BACKGROUND: The most important anti-tumor immune response is mediated by T lymphocytes. The interaction of programmed death-1 ligand-1 (PD-L1) with its receptor provides an inhibitory signal in T lymphocytes activation and proliferation. OBJECTIVE: This study aimed to investigate whether polymorphisms of PD-L1 were associated with the risk and prognosis of esophageal squamous cell carcinoma (ESCC) in a high-incidence population from Northern China. METHODS: PD-L1 rs2890658 A/C and rs4143815 C/G single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method in 575 ESCC patients and 577 healthy controls. …RESULTS: There was no significant difference in the genotype frequencies of these two SNPs between the ESCC patients and the healthy controls. However, for rs2890658 A/C SNP, compared with the C/C genotype, the A/C genotype increased the risk of ESCC for the smokers (OR = 1.513, 95% CI = 1.006–2.287). Among the 575 ESCC patients, the survival information of 202 ESCC patients was collected. Neither the rs2890658 A/C SNP nor the rs4143815 C/G SNP was associated with the survival of ESCC patients. CONCLUSIONS: PD-L1 rs2890658 A/C SNP might be used as risk marker of the susceptibility to ESCC for the Han nationality in a high-incidence population from Northern China. Show more

Keywords: Esophageal squamous cell carcinoma, programmed death-1 ligand-1, polymorphism, prognosis, risk

DOI: 10.3233/CBM-170269

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 65-71, 2018

Authors: Zhu, Xiaoqin | Chen, Fang | Shao, Yongfu | Xu, Dingli | Guo, Junming

Article Type: Research Article

Abstract: BACKGROUND: Accumulating evidences have shown that long non-coding RNAs (lncRNAs), longer than 200 nucleotides in length, play a crucial role in cancer occurrence and development. However, the relationships between most lncRNAs and gastric carcinogenesis remain poorly understood. OBJECTIVE: To explore the diagnostic value of one typical lncRNA, long intergenic non-protein coding RNA 1006 (LINC01006), in gastric cancer. METHODS: First, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression levels of LINC01006 in various gastric tissues from gastric cancer patients, healthy controls, and gastric dysplasia. Next, the correlation between LINC01006 …expression levels and clinicopathological features of patients with gastric cancer was assessed. Finally, the relative levels of LINC01006 in gastric cancer cell lines comparing to normal gastric epithelial cell line were analyzed. RESULTS: LINC01006 levels in cancer tissues were significantly lower than those in adjacent normal tissues (P < 0.001) and healthy control tissues (P < 0.001). Its expression was associated with age (P = 0.013), tumor location (P = 0.022), tumor size (P = 0.030), and venous invasion (P = 0.018). Moreover, expression of LINC01006 was downregulated in two gastric cancer cell lines, MGC-803 (P < 0.05) and AGS (P < 0.001) compared to normal gastric epithelial cell line GES-1. CONCLUSIONS: All the data implied that LINC01006 may be a novel biomarker for gastric cancer. Show more

Keywords: Cancer diagnosis, gastric cancer, long non-coding RNA, LINC01006, tumor biomarker

DOI: 10.3233/CBM-170273

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 73-80, 2018

Authors: Guo, Xiaojing | Liu, Yujie | Huang, Xia | Wang, Yun | Qu, Jin | Lv, Yingpin

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Relaxin is a short circulating peptide hormone. The aim of this study was to understand the role of relaxin in progression of epithelial ovarian cancer (EOC) and to assess its diagnostic and prognostic significance. METHODS: A total of 124 patients with EOC, 46 patients with benign ovarian diseases, and 50 healthy controls were recruited. Serum levels of relaxin were determined by ELISA method. The relationship between serum relaxin level and each of the clinicopathological parameters was analyzed using the χ 2 test. Survival curves were plotted using the Kaplan-Meier …method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: The results showed that serum relaxin level was significantly higher in patients with EOC than those with benign ovarian diseases and healthy controls (p < 0.01). Serum relaxin level was associated with FIGO stage, lymph node metastasis, tumor resectability, survival of the patients, chemotherapy and tumor recurrence (p < 0.05). Analysis using the Kaplan-meier method indicated that patients with high serum relaxin had significantly shorter overall survival time than those with low relaxin (p < 0.01). In a multivariate analysis along with clinical prognostic parameters, serum relaxin was identified as an independent adverse prognostic variable for survival. CONCLUSIONS: These results indicated that serum relaxin may be a clinically useful indicator for diagnostic and prognostic evaluation in EOC patients. Show more

Keywords: Epithelial ovarian cancer, metastasis, prognosis, marker, relaxin

DOI: 10.3233/CBM-170278

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 81-87, 2018

Authors: Zhang, Yijun | Jin, Xintian | Wang, Zhe | Zhang, Xiaokai | Liu, Shen | Liu, Gang

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) exert important functions involved in tumorigenesis and cancer progression including esophageal squamous cell cancer (ESCC), however, the clinical role and underlying biological function of Small Nucleolar RNA Host Gene 1 (SNHG1) in ESCC is not well known. METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) was used to detect the SNHG1 expression levels in ESCC tissues and adjacent non-cancerous tissues. Chi-square test was used to evaluate the association between clinicopathological features and SNHG1 expression in ESCC patients, Kaplan-Meier curve and log rank test was performed to analyze the association between overall survival …and SNHG1 expression. Cell proliferation and invasion was assessed by MTT assay, colony formation, and transwell cell invasion assays. Western blot were also performed to examine protein expression levels of E-cadherin, Vimentin and N-cadherin, Notch 1 and Hes-1. RESULTS: We demonstrated that lncRNA SNHG1 was significantly up-regulated in ESCC tissues compared with adjacent non-cancerous tissues in ESCC patients. Meanwhile, increased lncRNA SNHG1 expression levels markedly correlated with lymph node metastasis, depth of invasion, TNM stage and reduced over survival time in ESCC patients. Furthermore, MTT assay, colony formation, transwell cell invasion, qRT-PCR and Western-blot assays demonstrated that knockdown of lncRNA SNHG1 could inhibit cell proliferation and cell invasion capacity and cell Epithelial-Mesenchymal Transition (EMT) phenomenon by up-regulation E-cadherin and down-regulating Vimentin and N-cadherin in ESCC cells. Besides, we demonstrated that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 and Hes-1 expression levels in ESCC cells. CONCLUSIONS: These results indicated that lncRNA SNHG1 may be a potential predictor of prognosis in ESCC patients and a novel target for ESCC treatment. Show more

Keywords: Long non-coding RNA, esophageal squamous cell cancer, SNHG1, cell invasion, cell proliferation

DOI: 10.3233/CBM-170286

Citation: Cancer Biomarkers, vol. 21, no. 1, pp. 89-96, 2018