Cancer Biomarkers - Volume 22, issue 4

Authors: Zhou, Jian | Ge, Yuyuan | Hu, Yun | Rong, Dawei | Fu, Kai | Wang, Hanjin | Cao, Hongyong | Tang, Weiwei

Article Type: Other

Abstract: Circular RNAs (circRNAs), which were discovered as a special class of endogenous non-coding RNAs, have recently shown huge capabilities as gene regulators in different species in a wide variety of organisms including viruses, plants, archaea and animals. These circRNAs mainly arise from exons or introns in different combinations by special selective splicing and are enriched in cytoplasm. Apart from that, circRNAs usually display patterns of cell-type, tissue-type and developmental-stage specific expression in eukaryotic transcriptome. These findings hint at the vital function of circRNAs in development and diseases. Herein, we summarize the current understanding of the molecular characteristics of circRNAs and …discuss their proposed functions and mechanism-of-action in human diseases, animals as well as botanics. Show more

Keywords: Circular RNA, anti-cancer, diagnosis, botanics, animals

DOI: 10.3233/CBM-181296

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 597-610, 2018

Authors: Shakya, Manjul | Zhou, Aijun | Dai, Danian | Zhong, Qian | Zhou, Zhongguo | Zhang, Yaojun | Li, Xu | Bholee, Ashwin Kumar | Chen, Minshan

Article Type: Research Article

Abstract: BACKGROUND: Transforming acidic coiled-coil protein 2 (TACC2) is a member of TACC family proteins which is mainly involved in the stabilization of spindles and regulation of microtubule dynamics through interactions with molecules involved in centrosomes/microtubules. TACC2 is involved in tumorigenesis of variety of cancers but the clinical significance of TACC2 protein in hepatocellular carcinoma (HCC) is still unclear. OBJECTIVE: This study aims to investigate the expression of TACC2 in HCC and determine if clinical significance and prognostic relevance exists. METHODS: We performed quantitative PCR (qPCR) and western blot to examine TACC2 mRNA and …protein expression in paired HCC tissues and matched adjacent non-cancerous tissues. Immunohistochemistry was performed in 106 postoperative HCC samples. RESULTS: There was higher expression of TACC2 protein and mRNA in HCC tissue. Immunohistochemistry analysis showed high expression of TACC2 in HCC tissue and was significantly associated with the capsular extension, tumor recurrence and shortened overall and disease free survival. The Cox regression analysis suggested that a high expression of TACC2 was an independent prognostic factor for HCC patients. CONCLUSION: This finding suggests that TACC2 may be a useful tool as a candidate biomarker to predict the recurrence and prognosis of HCC. Show more

Keywords: Transforming acidic coiled-coil protein 2, hepatocellular carcinoma, prognosis, survival

DOI: 10.3233/CBM-170091

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 611-619, 2018

Authors: Liu, Hongqian | Cao, Bofeng | Zhao, Yuanyuan | Liang, Haijing | Liu, Xinfeng

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVES: MicroRNA (miR-221/222) is frequently overexpressed in many cancers and is associated with poor prognosis. However, the role of miR-221/222 in retinoblastoma (RB) remains unclear. This study aimed to detect the clinical significance of miR-221/222 in RB patients and explore its role in RB cells in vitro . METHODS: Expression of miR-221/222 was assessed in fresh RB tissue collected from 64 eyes and normal retinal tissues from 18 unrelated donor cadaver eyes by quantitative real time RT-PCR analysis (qRT-PCR), and correlated with the histopathological findings. Human RB Y79 cells were transfected with miR-221/222 precursors …or inhibitors to overexpress or downregulate miR-221/222 expression, respectively, using Lipofectamine 2000 reagent. The biological effects of miR-221/222 were then assessed by cell viability assays, colony formation assays, apoptosis detection assays, Matrigel ® invasion assays, and wound-healing assays. RESULTS: Higher miR-221/222 expression was detected in RB tissues compared to that of the normal retinal tissues (p < 0.001). Higher miR-221/222 expression was correlated with invasion in patients with RB. Targeting of miR-221/222 induced apoptosis and inhibited Y79 cell proliferation, migration, and invasion in vitro . However, overexpression of miR-221/222 promoted Y79 cell proliferation, migration, and invasion in vitro . CONCLUSIONS: Overexpression of miR-221/222 was associated with tumor invasiveness in patients with RB. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. Show more

Keywords: Retinoblastoma, miR-221/222, marker, invasion

DOI: 10.3233/CBM-170721

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 621-629, 2018

Authors: Wang, Shanshan | Cui, Shichang | Zhao, Wenming | Qian, Zhiling | Liu, Hui | Chen, Yuhan | Lv, Fudong | Ding, Hui-Guo

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNAs) play an important role in pathogenesis and development of hepatocellular carcinoma (HCC). However, circRNA expression profiles in hepatitis B Virus (HBV)-related HCC remain to be studied. METHODS: Total 13 HBV-related HCC patients were enrolled for study. Three HCC and 3 paired adjacent non-tumorous (NT) tissues from 3 patients were performed for microarray. Ten pairs of HCC tissues were used to verify the identified up-regulated and down-regulated circRNAs obtained from the microarray data by quantitative real-time reverse transcription PCR (qRT-PCR). Total RNA was isolated and treated with Rnase R to remove linear RNA, then hybridized to …the array to screen for circRNAs. Bioinformatics analyses including clustering, differential expression, annotation of circRNA/microRNA (miRNA) interactions, Go analysis and KEGG pathway analysis, were performed. RESULTS: Based on the microarray data, we found significantly up-regulation of 24 circRNAs and down-regulation of 23 circRNAs in the HCC samples compared to NT samples (fold change ⩾ 2.0 and P < 0.05). Of them, 6 candidate circRNAs (hsa_circRNA_102814, 100381, 103489, 101764, 100327, and 103361) were verified by qRT-PCR. Of them, hsa_circRNA 100381, 103489 up-regulation and 101764 down-regulation were found to be significantly different in the 10 validation HCC tissue. Clusters of circRNAs were aberrantly expressed in HCC compared with NT samples. CircRNA_101764 was the largest nodes in circRNA/microRNA co-expression network, especially co-expression with hsa-miR-181 family, which plays an important role in cell network. Annotation of circRNA/miRNA interactions indicated that the biological effects of circRNA may be achieved by binding of miRNAs. GO analysis revealed that numerous target genes were involved in the biological processes, cellular component and molecular function. There was nearly 30 target genes enrichment on KEGG pathways analysis, PI3K-Akt signaling pathway which the most number of genes involved. CONCLUSION: In this study, we comprehensively explored the expression of differentially expressed circRNAs in HBV-related HCC, and our results indicate that circRNA_101764 may play an important role in the development of HCC. Show more

Keywords: Hepatocellular carcinoma, HBV, circular RNA, microarray

DOI: 10.3233/CBM-170910

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 631-640, 2018

Authors: Gao, Jie | Shao, Zhongjun | Yan, Min | Fu, Ting | Zhang, Lei | Yan, Yongping

Article Type: Research Article

Abstract: STAT3 is an important molecule in Janus kinase (JAK) signal transducer and activator of transcription (STAT) signal pathway, and facilitates expression of various oncogenic genes such as Bcl-2, thus is correlated with tumor onset, progression and drug resistance. MiR-29a down-regulation is associated with the pathogenesis of nasopharyngeal carcinoma. Bioinformatics analysis demonstrated a complementary binding between miR-29a and 3’-UTR of STAT3. This study aims to investigate the role of miR-29a in regulating STAT3, as well as in Taxol resistance of nasopharyngeal carcinoma CNE-1 cells. Dual luciferase reporter gene assay showed a regulatory relationship between miR-29a and STAT3. Rhodamine 123 repository in …CNE-1 and CNE1/Taxol drug resistant cells was measured together with the expression of miR-29a, STAT3, and p-STAT3. Flow cytometry was used to measure cell apoptosis and PCNA expression under Taxol treatment. CNE-1/Taxol cells were treated with miR-29a mimic and or si-STAT3, followed by measuring the expression of miR-29a, STAT3, and p-STAT3 and cell apoptosis. CCK-8 assay was performed to evaluate cell proliferation. MiR-29a inhibited STAT3 expression. Significantly lower Rhodamine 123 repository, miR-29a expression and apoptosis and higher expression of STAT3, p-STAT3 and PCNA were observed in CNE-2/ Taxol cells than those in CNE-1 cells. Transfection of miR-29a mimic and/or si-STAT3 decreased STAT3, p-STAT3 and PCNA expression, inhibited proliferation and promoted cell apoptosis. MiR-29a down-regulation is correlated with drug resistance of nasopharyngeal carcinoma cell line CNE-1 and MiR-29a up-regulation decreases Taxol resistance of nasopharyngeal carcinoma CNE-1 cells possibly via inhibiting STAT3 and Bcl-2 expression. Show more

Keywords: MiR-29a, STAT3, taxol, nasopharyngeal carcinoma, drug resistance

DOI: 10.3233/CBM-170964

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 641-648, 2018

Authors: Liu, Chen-Guang | Cui, Xiao-Long | Wei, Zhi-Gang | Guo, Jian-Sheng

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer is one of the most common malignant tumours. Identifying novel genes that govern the development of gastric cancer will help to elucidate its molecular mechanisms and find novel biomarkers. METHODS: Expression of the ANKRD49 protein was assessed by immunohistochemical analysis of tissue microarrays containing 92 sets of human gastric cancer specimens with adjacent non-cancerous tissue. Associations between ANKRD49 levels and clinicopathological characteristics of the patient were investigated. The correlation between ANKRD49 expression and patient survival was analysed by the Kaplan-Meier method. RESULTS: The results revealed that the expression level of the …ANKRD49 protein in gastric cancer was significantly upregulated and correlated with the tumour size, tumour-node-metastasis (TNM) stage, histological grade, depth of invasion, vessel invasion, lymph node metastasis and distant metastasis. The mean survival time of patients with low expression levels of ANKRD49 was significantly longer than that of patients with high expression levels of ANKRD49. Multivariate Cox regression analysis demonstrated that the ANKRD49 protein expression level was an independent prognostic indicator for the survival rate of patients with gastric cancer. CONCLUSION: The results of the present study highlighted an important role of the ANKRD49 protein in the progression of gastric cancer. The ANKRD49 protein could act as a potential biomarker for prognosis evaluation of gastric cancer and may be used as a molecular target for gastric cancer treatment. Show more

Keywords: ANKRD49, gastric cancer, tissue microarray, immunohistochemistry, prognosis

DOI: 10.3233/CBM-171074

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 649-656, 2018

Authors: Mlak, Radosław | Powrózek, Tomasz | Brzozowska, Anna | Homa-Mlak, Iwona | Mazurek, Marcin | Małecka-Massalska, Teresa

Article Type: Research Article

Abstract: BACKGROUND: Intensified treatment of head and neck cancers (HNC): by radiotherapy (RTH) commonly combined with cytotoxic drugs is associated with oral mucositis (OM). Changes in the functioning of nucleotide synthesis pathway (RNR1, coded by RRM1 gene) can modulate the efficiency of cellular DNA repair mechanisms and influence the risk of occurrence and severity of OM in HNC patients after RTH. OBJECTIVE: The objective of this study was to evaluate the correlation between expression of RRM1 gene measured in free circulating RNA (cfRNA) and the risk of more severe OM and disease-free survival (DFS) and …overall survival (OS) in patients undergoing RTH for HNC. METHODS: The study included 60 patients treated with RTH for HNC. RRM1 gene expression was examined in circulating RNA isolated from peripheral blood plasma (before treatment). RESULTS: High RRM1 gene expression was significantly associated with higher risk of grade 3 OM after 5 (OR = 4.97), 6 (OR = 4.33) and 7 (OR = 3.50) weeks of RTH. Expression of RRM1 gene was not significantly related with risk of DFS and OS shortening (however well separated Kaplan-Meier curves might suggest its potential prognostic impact). CONCLUSIONS: The evaluation of RRM1 gene expression in cfRNA allows for estimation of the risk of severe OM in patients subjected to RTH. Show more

Keywords: cfRNA, DNA repair, head and neck cancer, liquid biopsy, oral mucositis, radiotherapy, RRM1, survival

DOI: 10.3233/CBM-171082

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 657-667, 2018

Authors: Shu, Jian | Yu, Hanjie | Du, Haoqi | Zhang, Jiaxu | Zhang, Kun | Li, Xiaojie | Xie, Hailong | Li, Zheng

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Gastric cancer (GC) is a common and fatal malignancy with a worldwide occurrence. There still lacks effective biomarkers for precisely evaluating GC. Saliva is a biological fluid with enormous diagnostic potentials which emerged many advantages. We aimed to discover the novel biomarkers for accurately distinguishing early GC based on saliva glycopatterns. METHODS: We used Aleuria Aurantia Lectin (AAL)-magnetic particle conjugates to isolate fucosylated glycoproteins in the pooled saliva of healthy volunteers (HV, n = 51) and patients with atrophic gastritis (AG, n = …51) or GC (n = 51), following to release the N - and O -linked glycans from the isolated proteins with PNGase F and NaClO, and further identified the released glycans by MALDI-TOF/TOF-MS, respectively. RESULTS: A total of 9/9, 8/11, and 9/9 fucosylated N -/O -linked glycans were annotated in the isolated salivary proteins from HV, AG, and GC, respectively. Among these, six fucosylated N -linked glycansand four O -linked glycans exhibited significantly increased expression levels in GC, while five fucosylated N -linked glycans and ten fucosylated O -linked glycans exhibited significantly decreased expression levels in GC. The proportion of fucosylated N -linked glycans was decreased in GC (41.66%) compared with AG (43.63%) and HV (52.57%), as well as the fucosylated O -linked glycans was apparently decreased in GC (19.58%) compared with AG (25.43%) and HV (55.54%). CONCLUSIONS: This study could provide pivotal information to distinguish among HV, AG, and GC, and facilitate the discovery of biomarkers for GC diagnosis based on precise alterations of N - and O -linked glycans in saliva. Show more

Keywords: Saliva, gastric cancer, MALDI-TOF/TOF-MS/MS, N- and O-Linked glycan

DOI: 10.3233/CBM-171087

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 669-681, 2018

Authors: Wang, Lijun | Wu, Qi | Zhu, Shan | Li, Zhiyu | Yuan, Jingping | Liu, Lin | Yu, Dehua | Xu, Zhiliang | Li, Juanjuan | Sun, Shengrong | Wang, Changhua

Article Type: Research Article

Abstract: DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The prognostic value of DNER in prostate cancer has not been evaluated. Here we showed that the up-regulation of DNER protein was observed in prostate cancer detected by immunohistochemistry (IHC) and quantum dot-based immunofluorescent imaging and quantitative analytical system (QD-IIQAS). However, a higher accuracy of measurements of DNER expression in prostate cancer was found by QD-IIQAS than by IHC (AUC = 0.817 and 0.617, respectively). DNER was significantly higher in patients undergoing bone metastasis (P = 0.045, RR …= 3.624). In addition, DNER overexpression was associated with poor overall survival (OS) (P = 0.028, adjusted HR = 8.564) and recurrence-free survival (RFS) (P = 0.042, adjusted HR = 3.474) in patients suffering prostate cancer. Thus, QD-IIQAS is an easy and accurate method for assessing DNER and the DNER expression was an independent prognostic factor in prostate cancer. Show more

Keywords: Quantum dot-based immunofluorescent imaging, DNER, prognostic value, prostate cancer

DOI: 10.3233/CBM-171107

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 683-691, 2018

Authors: Liu, Dengxiang | Wang, Na | Sun, Yawei | Guo, Ting | Zhu, Xiaoyan | Guo, Jun

Article Type: Research Article

Abstract: OBJECTIVE: To analysis the expression of VEGF in gastric carcinoma cell and tumor tissue, our study determined the relationship between the expression of VEGF and tumor incidence, metastasis and prognosis in human gastric carcinoma. METHODS: Treatment of ZD6474 at dose of 30 μ mol/L was performed in gastric carcinoma cell BGC823. qPCR and Western-blot were used to analysis the mRNA and protein expression of VEGF. MTT, wound healing and Transwell experiments were conducted to study the effect of VEGF on tumor incidence, metastasis and prognosis. Sixty patients with gastric cancer were selected as the gastric …cancer group, and 30 patients with gastric ulcer receiving main gastric resection were selected as control group. The survival curve of patients with gastric cancer in five years was recorded. The correlation between expression of VEGF to incidence, metastasis and prognosis of gastric cancer was evaluated by Cox multifactor regression. RESULTS: The mRNA and protein expression of VEGF in treatment group were significantly lower than that of control group (P < 0.01). The results of MTT, wound healing and Transwell experiments were showed that the cell proliferation, migration and invasion capacity in treatment group were significantly reduced compared to that of the control group (P < 0.01). The 5-year survival rate for patients with VEGF positive expression was significantly decreased compared to the patients with VEGF expression negative (P < 0.01). The tumor size, differentiation, lymph node metastasis and tumor stage were statistically related to VEGF level (P < 0.05). The results of Cox regression multifactor analysis showed that lymph node metastasis, tumor staging and the expression of VEGF were significantly associated to the prognosis of gastric cancer patients (P < 0.05). CONCLUSION: Our data demonstrated that the expression of VEGF was significantly related to the tumor incidence, metastasis and prognosis of patients with gastric cancer, which provides new leads to the diagnosis of gastric cancer. Show more

Keywords: Gastric carcinoma, VEGF, prognosis, metastasis

DOI: 10.3233/CBM-171163

Citation: Cancer Biomarkers, vol. 22, no. 4, pp. 693-700, 2018