Cancer Biomarkers - Volume 22, issue 1

Authors: Yan, Jinhua | Wu, Guohe | Chen, Jianlan | Xiong, Lifang | Chen, Guoan | Li, Ping

Article Type: Research Article

Abstract: BACKGROUND: Circulating microRNAs (miRNAs) play an essential role in the development and progression of acute myeloid leukemia (AML). However, the clinical value of serum miR-217 in AML remained poorly known. OBJECTIVE: This study aimed to explore the clinical significance of serum miR-217 in AML. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to detect miR-217 levels in the blood samples obtained from 89 AML patients and 60 healthy controls. RESULTS: The results showed that miR-217 expression was significantly decreased in AML patients compared to controls. Likewise, serum miR-217 levels were greatly downregulated …in the AML patients with poor risk cytogenetic. ROC analysis demonstrated that serum miR-217 could effectively differentiate AML patients from normal controls. Also, miR-217 expression was markedly increased in patients achieving complete remission after their treatment. In addition, low miR-217 expression was associated with aggressive clinical features. Moreover, Kaplan-Meier analysis showed that AML patients with low miR-217 expression tended to have shorter overall survival and disease free survival. In the multivariate analysis stratified for prognostic parameters, miR-217 was proved to be an independent prognostic indicator. CONCLUSIONS: Collectively, miR-217 was identified as an independent marker for the diagnosis and prognosis of AML. Show more

Keywords: Acute myeloid leukemia, prognostic biomarker, miR-217, serum

DOI: 10.3233/CBM-170936

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 73-78, 2018

Authors: Guo, Tao | Pan, Guobiao

Article Type: Research Article

Abstract: BACKGROUND: Accumulating studies have reported the abnormal expression of microRNA-136 (miR-136) in numerous types of human cancer, and its involvement in cancer initiation and progression. However, there are no investigations of miR-136 in osteosarcoma (OS). OBJECTIVE: To explore the expression pattern, clinical significance and potential roles of miR-136 in OS. METHODS: miR-136 expression in clinical OS tissues and human OS cell lines were detected by qPCR, and its associations with clinicopathological characteristics of OS patients were statistically analyzed. Then, the effects of miR-136 on OS cell proliferation, migration and invasion were assessed in vitro . …Its underling mechanisms were also investigated. RESULTS: miR-136 expression in OS tissues and cells were dramatically decreased compared with corresponding non-cancerous tissues and cells, respectively. Low miR-136 expression was significantly associated with aggressive clinical features, including the advanced clinical stage, the presence of lung and distant metastasis (all P < 0.05). Additionally, enforced expression of miR-136 obviously inhibited the proliferation, migration and invasion of OS cells in vitro . Mechanistically, metadherin (MTDH) was predicted and verified as a target gene of miR-136. Further functional experiments indicated that the loss of MTDH abrogated the tumor suppressive roles of miR-136 in OS cells. CONCLUSION: Our findings provide the first evidence that the aberrant expression of miR-136 may be implicated into carcinogenesis and cancer progression of OS. Functionally, miR-136 may inhibit the proliferation, migration and invasion of OS cells via negatively regulating its target gene MTDH. Thus, miR-136-MTDH axis may be a potential therapeutic targets for the treatment of OS. Show more

Keywords: Osteosarcoma, microRNA-136, metadherin, clinicopathologic characteristics, proliferation, migration, invasion

DOI: 10.3233/CBM-170970

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 79-87, 2018

Authors: Janikowska, Grażyna | Janikowski, Tomasz | Pyka-Pająk, Alina | Mazurek, Urszula | Janikowski, Marcin | Gonciarz, Maciej | Lorenc, Zbigniew

Article Type: Research Article

Abstract: BACKGROUNDS: Colorectal cancer is the third most common cancer in economically developed countries. Molecular studies and, in particular, gene expression have contributed to advances in the diagnosis and treatment of many cancers. Genes can be molecular and therapeutic markers, but because of the large molecular diversity in colorectal cancer the knowledge is not yet fully established. Probably one of the most crucial processes during early cancer development is inflammation. The inflammatory response in the tumor is an important indicator of molecular etiology and later of cancer progression. OBJECTIVE: The aim of this work is to identify …potential biomarkers for early stage of colorectal adenocarcinoma in patients’ bowel tissues using transcriptomic analysis. METHODS: Expression of the inflammatory response genes of colorectal cancer at all clinical stages (I–IV) and control of the bowel were evaluated by oligonucleotide microarrays. RESULTS: Based on statistical analysis many differentially expressed genes were selected. LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase), GNLY (granulysin), SLC6A6 (Solute-Carrier Family 6 Member 6) and LAMP2 (Lysosomal Associated Membrane Protein 2) were specific for the early stage of the disease. These genes had the properties of the good biomarkers. CONCLUSIONS: The expression of LCK , GNLY , SLC6A6 and LAMP2 genes could be valuable potential diagnostic biomarkers of the early stage of colorectal adenocarcinoma. Show more

Keywords: Colorectal adenocarcinoma, clinical stage, microarray, LCK, GNLY, SLC6A6, LAMP2, biomarkers

DOI: 10.3233/CBM-170984

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 89-99, 2018

Authors: Krejcik, Zdenek | Belickova, Monika | Hrustincova, Andrea | Votavova, Hana | Jonasova, Anna | Cermak, Jaroslav | Dyr, Jan E. | Merkerova, Michaela Dostalova

Article Type: Research Article

Abstract: BACKGROUND: Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction of AZA responsiveness is important for the therapy management. METHODS: Using microarrays and reverse-transcription quantitative-PCR, we analyzed microRNA (miRNA) expression in bone marrow CD34+ cells of 27 patients with higher-risk myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia-related changes before and during AZA treatment. RESULTS: At baseline, we found that future overall response rate was significantly higher in patients with upregulated miR-17-3p and downregulated miR-100-5p and miR-133b. Importantly, the high level of miR-100-5p at baseline was associated with …shorter overall survival (HR = 4.066, P = 0.008). After AZA treatment, we observed deregulation of 30 miRNAs in responders (including downregulation of miR-10b-5p, miR-15a-5p/b-5p, miR-24-3p, and miR-148b-3p), while their levels remained unchanged in non-responders. CONCLUSIONS: Our study demonstrates that responders and non-responders have distinct miRNA patterns and that the level of specific miRNAs before therapy may predict the efficacy of AZA treatment. Show more

Keywords: Myelodysplastic syndromes, microRNA, azacitidine, response prediction

DOI: 10.3233/CBM-171029

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 101-110, 2018

Authors: Wu, Yuanyu | Wan, Xiaoyu | Ji, Fujian | Song, Zheyu | Fang, Xuedong

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

Keywords: Met proto-oncogene, metastasis of gastric carcinoma, miR-658, paired box gene 3

DOI: 10.3233/CBM-171045

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 111-118, 2018

Authors: Feng, Runhua | Beeharry, Maneesh K. | Lu, Sheng | Sah, Birendra K. | Yuan, Fei | Yan, Min | Liu, Bingya | Li, Chen | Zhu, Zhenggang

Article Type: Research Article

Abstract: BACKGROUND: miR-126 functions as a tumor suppressor in gastric cancer (GC), however, the clinical significance of serum miR-126 in GC remains unclear. OBJECTIVE: To investigate the associations of serum miR-126 level with the clinicopathological characteristics and prognosis of GC patients. METHODS: Quantitative real-time polymerase chain reaction was performed to examine the expression levels of miR-126 in 338 GC patients’ tissues and sera, and 50 healthy controls’ sera. The associations of serum miR-126 with clinicopathological characteristics and clinical outcome were evaluated. RESULTS: Compared with the matched adjacent non-tumor tissues and normal sera, miR-126 expression was …significantly down-regulated in both tumor tissues and sera of GC patients. Importantly, there was a positive correlation between tissue and serum levels of miR-126 in GC patients. A reduced serum miR-126 level statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Notably, multivariate analysis identified reduced serum miR-126 level as an independent predictor for the unfavorable prognosis of GC. CONCLUSIONS: These results indicate for the first time that serum miR-126 may serve as a novel prognostic biomarker in GC. Show more

Keywords: Gastric cancer, microRNA, miR-126, serum, prognosis

DOI: 10.3233/CBM-171099

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 119-126, 2018

Authors: Yao, Z.-S. | Li, C. | Liang, D. | Jiang, X.-B. | Tang, J.-J. | Ye, L.-Q. | Yuan, K. | Ren, H. | Yang, Z.-D. | Jin, D.-X. | Zhang, S.-C. | Ding, J.-Y. | Tang, Y.-C. | Xu, J.-X. | Chen, K. | Xie, W.-X. | Guo, D.-Q. | Cui, J.-C.

Article Type: Research Article

Abstract: Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 …expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma. Show more

Keywords: MiR-101, serum, osteosarcoma, biomarker

DOI: 10.3233/CBM-171103

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 127-133, 2018

Authors: Zhang, Xianwei | Qiu, Shili | Luo, Ping | Zhou, Hu | Jing, Wei | Liang, Chuizi | Tu, Jiancheng

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNA)are involved in the progression of cancers, and previous study showed that hsa_circ_0001649 expression is down-regulated in hepatocellular carcinoma (HCC). OBJECTIVE: To explore whether hsa_circ_0001649 is a prognostic biomarker for HCC and to investigate the biological functions of hsa_circ_0001649 in HCC. METHODS: Hsa_circ_0001649 expression was measured in 77 pairs of HCC and adjacent no-tumor tissues by quantitative Real-Time polymerase chain reaction. Kaplan-Meier curve and Cox regression were used to analyze its prognostic significance for HCC patients. In addition, the hsa_circ_0001649 was over-expressed using a circRNA-forming plasmid in HCC cells, and the biological …function of hsa_circ_0001649 was investigated in vitro . RESULTS: We verified that hsa_circ_0001649 was down-regulated in HCC tissues compared with adjacent non-tumor tissues. In addition, low hsa_circ_0001649 expression was associated with the poor overall survival of HCC patients, and Cox multivariate analysis showed that hsa_circ_0001649 is a novel independent prognostic factor for HCC patients. Furthermore, the in vitro experiments demonstrated that over-expressed hsa_circ_0001649 inhibits the proliferation, migration, and invasion and promotes the apoptosis of HCC cells. CONCLUSIONS: Hsa_circ_0001649 could act as a novel prognostic biomarker for HCC patients. In addition, hsa_circ_ 0001649 might be a potential therapeutic target for HCC. Show more

Keywords: Hsa_circ_0001649, hepatocellular carcinoma, prognosis, biomarker

DOI: 10.3233/CBM-171109

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 135-142, 2018

Authors: Bozkaya, Yakup | Özdemir, Nuriye Yıldırım | Sezer, Sevilay | Köstek, Osman | Demirci, Nebi Serkan | Yazıcı, Ozan | Erdem, Gökmen Umut | Eren, Tülay | Zengin, Nurullah

Article Type: Research Article

Abstract: BACKGROUND: The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE: Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS: Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS : Median survivin level …was 147 IU/L (range = 4.4–4936) at baseline and was 27 IU/L (range = 4.2–4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8–1430) and pre-treatment patient group was statistically significant (p < 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p = 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p < 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p = 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p = 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p = 0.14). CONCLUSION: It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results. Show more

Keywords: Modified DCF, locally advanced gastric cancer, neoadjuvant chemotherapy, survivin, predictive

DOI: 10.3233/CBM-171119

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 143-149, 2018

Authors: Zhang, Yongyu | Yang, Lewei | Wang, Shiji | Liu, Zhongmin | Xiu, Ming

Article Type: Research Article

Abstract: OBJECTIVES: MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a acts as tumor suppressor in hepatocellular carcinoma (HCC) progression. However, the underlying functions for miR-29a in HCC still to be investigated. METHODS: The expression of miR-29a expression in HCC tissues and corresponding adjacent normal tissues was detected using qRT-PCR analyses. Cell proliferation ability was assessed using CCK8 assay, cell colony forming and flow cytometry analysis. Bioinformatics, the dual luciferase reporter assay, qRT-PCR and western blot analysis …were used to demonstrate that SIRT1 was a target of miR-29a. RESULTS: Here, we demonstrated that miR-29a was significantly downregulated in HCC tissues compared with corresponding adjacent normal tissues. Lower miR-29a expression associated with tumor size and vascular invasion of HCC. Furthermore, Lower miR-29a predicted a poor disease free survival (DFS) and overall survival (OS) time for HCC patients. Function assays showed that overexpression of miR-29a effectively suppressed cell proliferation, cell colony forming ability, and cell cycle progression. MiR-29a overexpression also inhibited the cell cycle related protein expression of CyclinD1 and CDK4, but increasing the P21 expression. Furthermore, Bioinformatics and the dual luciferase reporter assay analysis results demonstrated that miR-29a specifically targeted the 3’-UTR of SIRT1 mRNA and regulated its protein expression. Increased SIRT1 expression rescued the inhibited effects induced by miR-29a overexpression in HCC cells. CONCLUSIONS: Thus, these results indicated that miR-29a may serve as a potential target of HCC treatment. Show more

Keywords: Hepatocellular carcinoma, miR-29a, SIRT1, cell proliferation, prognosis

DOI: 10.3233/CBM-171120

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 151-159, 2018

Authors: Chang, Shu-Jian | Ge, Xiao-Song | Xu, Zhen-Yu | Qi, Xiao-Wei | Chen, Xiao-Ping

Article Type: Research Article

Abstract: BACKGROUND: Adjuvant chemotherapy plays important role in the comprehensive treatment of patients with stage III colorectal cancer. However, there is few molecular markers for predicting the therapeutic effect. OBJECTIVE: To identify factors that could predict adjuvant chemotherapy benefits in patients with stage III colorectal cancer. Methods: The medical records of 294 patients were reviewed and analyzed using the Kaplan–Meier method and Cox analysis. RESULTS: Lower CA125 (⩽ 35 u/ml, P = 0.0015) serum levels, stage IIIa (P = 0.0027), …1-3 positive lymph nodes (P = 0.0256), negative vascular invasion (P = 0.0215), lower CA199 (⩽ 27 u/ml, P = 0.0038) serum levels, and wild-type BRAF status (P = 0.0125) were significantly associated with a higher 2-year DFS rate in patients with stage III colorectal cancer. However, in multivariate COX analysis, the association remained significant only for CA125 levels (vs. ⩽ 35 u/ml group, HR 3.341; 95% CI, 1.198–9.316; P = 0.0212), vascular invasion (vs. negative vascular invasion, HR, 2.349; 95% CI, 1.227–4.499; P = 0.01), and BRAF (V600E) (vs. wild Braf, HR, 7.794; 95% CI, 1.867–32.531; P = 0.0049). CONCLUSION: Lower CA125 serum levels, negative vascular invasion, and wild-type BRAF status were significantly associated with improved 2-year DFS rates among patient with stage III disease who received adjuvant chemotherapy. Show more

Keywords: CA125, vascular invasion, BRAF, adjuvant chemotherapy, colorectal cancer

DOI: 10.3233/CBM-181179

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 161-168, 2018

Authors: Wang, Libin | Wang, Feng | Na, Li | Yu, Jingjing | Huang, Liya | Meng, Zhi-Qiang | Chen, Zhen | Chen, Hao | Ming, Liu-Lu | Hua, Yong-Qiang

Article Type: Research Article

Abstract: BACKGROUND: Recent study revealed that abnormal long noncoding RNAs (lncRNAs) expression are association with chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC). OBJECTIVE: The present study was aimed to investigate the effects of lncRNA AB209630 expression for gemcitabine resistance in PDAC cells. METHODS: In the study, increased expression of lncRNA AB209630 could suppress cell proliferation and cell colony formation ability in gemcitabine resistance cells of PDAC. Furthermore, western blot results demonstrated that upregulation of lncRNA AB209630 suppressed the PI3K/AKT signaling pathway in gemcitabine resistance cells. Besides, we found that lncRNA AB209630 expression was dramatically …downregulated in PDAC tissues compared to adjacent normal tissues. Lower PDAC expression predicted a poor prognosis in PDAC patients. CONCLUSIONS: Thus, these results indicated that lncRNA AB209630 may be a potential target of PDAC. Show more

Keywords: Pancreatic ductal adenocarcinoma, long non-coding RNA, AB209630, gemcitabine resistance, PI3K/AKT signaling

DOI: 10.3233/CBM-181182

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 169-174, 2018

Article Type: Research Article

DOI: 10.3233/CBM-179671

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 175-, 2018

Article Type: Research Article

DOI: 10.3233/CBM-179650

Citation: Cancer Biomarkers, vol. 22, no. 1, pp. 177-, 2018