Cancer Biomarkers - Volume 21, issue 2

Authors: Xu, Xiaohui | Cao, Lei | Zhang, Ye | Lian, Hongjian | Sun, Zhiwei | Cui, Yushang

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM229007.

Keywords: microRNA-1246, lung cancer, cell invasion, epithelial mesenchymal transition, CXCR4

DOI: 10.3233/CBM-170317

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 251-260, 2018

Authors: He, H.W. | Wang, N.N. | Yi, X.M. | Tang, C.P. | Wang, D.

Article Type: Research Article

Abstract: BACKGROUND: colorectal cancer (CRC) is the second leading cause of cancer and cancer-related death in the world. Noninvasive biomarkers for early diagnosis of CRC are highly demanded. OBJECTIVE: The up-regulation of specific microRNAs (miRNAs) in serum has been considered a promising biomarker of CRC and miR-24-2 may be a potential biomarker in the diagnosis the progression of CRC. METHODS: Sixty-eighty healthy subjects and 228 CRC patients were divided into six groups: control group, CRC 0, CRC I, CRC II, CRC III, CRC IV and CRC V. Serum level of miR-24-2 was measured by …real-time qPCR. Serum lipid profiles and oxidative-related molecules were also measured. RESULTS: Serum levels of miR-24-2 in CRC patients were significantly higher than healthy subjects (p < 0.05). In addition, the expression level of the miR-24-2 was decreased with the progression of CRC and reached the lowest level in CRC V. Spearman Rank Correlation analysis showed that miR-24-2 level was negatively related to the levels of superoxide dismutase (SOD) and reduced glutathione (GSH), aspartate transaminase (AST), alanine transaminase (ALT), cholesterol and triglyceride (p < 0.05). CONCLUSIONS: Serum miR-24-2 is a potential negative biomarker in the diagnosis of the progression of CRC patients and associated with biochemical indices. Show more

Keywords: miR-24-2, colorectal cancer, diagnostic biomarker, qRT-PCR

DOI: 10.3233/CBM-170321

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 261-267, 2018

Authors: Hong, Ze | Zhang, Rongrong | Qi, Haixiao

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA-195 acts as a tumor suppressor in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) remains largely undefined. OBJECTIVE: To investigate the diagnostic and prognostic relevance of miR-195 in this malignancy. METHODS: Expression levels of miR-195 in peripheral blood and bone marrow samples of patients with pediatric AML and normal controls were detected by real-time quantitative PCR. Then, receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression analysis were performed to evaluate the diagnostic and prognostic relevance of serum miR-195 in pediatric AML. …RESULTS: Compared to normal controls, the expression levels of miR-195 in both bone marrow and patients’ sera were significantly decreased (both P < 0.001). In addition, serum miR-195 had an optimal diagnostic cut-off point (2.09) for pediatric AML with sensitivity of 68.87% and specificity of 96.23%. The area under the ROC curve (AUC) based on serum miR-195 was 0.910. Moreover, patients with low serum miR-195 level more often had French-American-British classification subtype M7 (P = 0.02), unfavorable karyotypes (P = 0.01), and shorter relapse-free and overall survivals (both P = 0.001) than those with high serum miR-195 level. Furthermore, the multivariate analysis identified serum miR-195 level as an independent prognostic factor for both relapse-free and overall survivals. CONCLUSION: The findings of this study suggest that the aberrant expression of miR-195 may play crucial roles in the development and progression of pediatric AML patients. Serum miR-195 may serve as a promising marker for monitoring the occurrence of this disease and predicting the clinical outcome of patients. Show more

Keywords: Pediatric acute myeloid leukemia, microRNA-195, serum, real-time quantitative PCR, prognosis

DOI: 10.3233/CBM-170327

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 269-275, 2018

Authors: Liao, Xinhui | Chen, Jieqing | Liu, Yuchen | He, Anbang | Wu, Jianting | Cheng, Jianli | Zhang, Xintao | Lv, Zhaojie | Wang, Feng | Mei, Hongbing

Article Type: Research Article

Abstract: OBJECTIVES: To study the expression pattern of long non-coding RNA FGFR3 antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer. METHODS: The differential expression levels of FGFR3-AS1 and FGFR3 in tumor tissues and paired normal tissues were determined using Real-Time qPCR in a total of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson’s coefficient correlation was used for expression correlation assay. Expression differences of FGFR3-AS1 were analyzed according to grading and staging. FGFR3 protein was detected by western blot assay. Human bladder cancer T24 and …5637 cell lines were transiently transfected with FGFR3-AS1-specific siRNA or negative control siRNA. The cell proliferation changes of transfected bladder cancer cells were determined using CCK-8 assay. Apoptosis caused by knockdown of FGFR3-AS1 was evaluated using ELISA assay. Motility changes induced by knockdown of FGFR3-AS1 were measured using wound healing assay and transwell assay. RESULTS: Both FGFR3-AS1 and FGFR3 were overexpressed in bladder cancer tissues compared to matched normal tissues. They were also positively expressed in bladder cancer. FGFR3-AS1 expression levels were higher in high grade tumors than those in low grade tumors. FGFR3-AS1 expression levels were higher in invasive tumors than those in non-invasive tumors. Cell proliferation inhibition, increased apoptosis, and decreased motility were observed in FGFR3-AS1 siRNA-transfected T24 and 5637 cell lines. CONCLUSIONS: FGFR3-AS1 plays an oncogenic role in human bladder cancer. Knockdown of FGFR3-AS1 may provide a potential new therapeutic approach to this disease. Show more

Keywords: lncRNA, FGFR3-AS1, bladder cancer

DOI: 10.3233/CBM-170354

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 277-285, 2018

Authors: Tan, Dan | Sheng, Li | Yi, Qing-Hua

Article Type: Research Article

Abstract: OBJECTIVE: To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. METHODS: A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. RESULTS: PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk …for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1 /PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. CONCLUSION: PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer. Show more

Keywords: Ovarian cancer, PD-1, PD-L1, polymorphism, clinicopathologic features, prognosis

DOI: 10.3233/CBM-170357

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 287-297, 2018

Authors: Sun, Handong | Tang, Weiwei | Rong, Dawei | Jin, Hui | Fu, Kai | Zhang, Wenling | Liu, Zhaojing | Cao, Hongyong | Cao, Xiufeng

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNAs) have been found playing important roles in regulating cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we are aimed to investigate the relationship between a new circular RNA named hsa_circ_0000520 and gastric cancer development. METHODS: The hsa_circ_0000520 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue, cell and plasma levels, respectively. Then, the association between the expression level of hsa_circ_0000520 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of …hsa_circ_0000520-miRNA-mRNA interactions was predicated. RESULTS: In this study, hsa_circ_0000520 was first found to be significantly down-regulated in gastric cancer tissues, plasma and gastric cancer cell lines compared with control cases. Clinicopathological features showed that hsa_circ_0000520 level in GC tissues was negatively associated with TNM stage and in GC plasma linked with CEA expression. Finally, a total of 9 miRNAs and 9 candidate mRNA were predicted to have an interaction with hsa_circ_0000520. CONCLUSIONS: We first identified that hsa_circ_0000520 was significantly down-regulated in gastric cancer. Our study indicated hsa_circ_0000520 might serve as a novel biomarker for gastric cancer and is involved in gastric carcinoma development. Show more

Keywords: Gastric cancer, hsa_circ_00000520, diagnosis, miRNA, mRNA

DOI: 10.3233/CBM-170379

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 299-306, 2018

Authors: Ji, Juanli | Zhen, Weiguo | Si, Yuan | Ma, Wenjing | Zheng, Lanlan | Li, Chen | Zhang, Yonghong | Qin, Shanshan | Zhang, Te | Liu, Pengfei | Zheng, Xin | Liu, Ying

Article Type: Research Article

Abstract: BACKGROUND: The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which involves in the progression of several human malignancies. Development of cisplatin (DDP) resistance is the obstacle to an effective control of gastric cancer (GC) clinically. OBJECTIVE: We thus assessed whether CIP2A expression is associated with sensitivity of GC to DDP. METHODS: Real-time quantitative PCR, immunohistochemical analysis, or western blotting was performed to detect CIP2A expression in GC patients’ tissues. SGC7901/DDP cells were transfected with CIP2A siRNA. MTT assay was used to determine the DDP-sensitivity of cells. Flow cytometry was used …to measure cell apoptosis. RESULTS: CIP2A has higher expression in DDP-resistant GC patients. DDP-resistant GC patients with high CIP2A expression presented with poorer overall survival rates than those with low CIP2A expression. CIP2A knockdown in DDP-resistant GC cells resulted in attenuated proliferative abilities and increased apoptosis level. CIP2A depletion sensitizes DDP-resistant cells to DDP and CIP2A overexpression antagonizes DDP-sensitive cells to DDP. CIP2A influences the expression of multidrug resistance-related proteins in GC cells. CONCLUSIONS: Our results suggested that CIP2A oncoprotein plays an important role in DDP resistance of GC and could serve as a novel therapeutic target for the treatment of GC patients with DDP resistance. Show more

Keywords: CIP2A, gastric cancer, DDP, chemoresistance, apoptosis

DOI: 10.3233/CBM-170416

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 307-316, 2018

Authors: Fu, Shuang | Niu, Ye | Zhang, Xin | Zhang, Ji-Rong | Liu, Zhi-Ping | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Squamous cell cervical carcinoma is the most common gynecological malignant disorder worldwide. Early detection of squamous cell cervical carcinoma is needed for proper clinical management. Squamous cell carcinoma antigen (SCCA) is commonly used as a tumor marker for squamous cell cervical carcinoma. Platelet distribution width (PDW) is an indicator of platelet activation. Prealbumin is a negative acute-phase protein. OBJECTIVE: The aim of this study was to investigate the ability of SCCA, PDW, and prealbumin individually or in combination, to distinguish between cervical carcinoma and control subjects. MEHTODS: Two hundred and twenty patients …with squamous cell cervical carcinoma and 211 control subjects were included in the study. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. RESULTS: Our results showed that SCCA and PDW were higher, and prealbumin was lower in cervical carcinoma patients than in control subjects. Single biomarker had AUC value ranging from 0.753 for SCCA to 0.845 for PDW. The combination of SCCA and PDW increased the AUC to 0.900 (p < 0.0001). In addition, the combination of SCCA, PDW and prealbumin exhibited a significantly larger AUC of 0.917 (0.887–0.942), significantly higher than those of any single marker. CONCLUSIONS: The combined use of SCCA, PDW and prealbumin can accurately distinguish squamous cell cervical carcinoma from control subjects. This promising approach could be helpful in early detection of squamous cell cervical carcinoma. Show more

Keywords: Cervical carcinoma, platelet distribution width, prealbumin, squamous cell carcinoma antigen

DOI: 10.3233/CBM-170442

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 317-321, 2018

Authors: Masetti, Michele | Acquaviva, Giorgia | Visani, Michela | Tallini, Giovanni | Fornelli, Adele | Ragazzi, Moira | Vasuri, Francesco | Grifoni, Daniela | Di Giacomo, Simone | Fiorino, Sirio | Lombardi, Raffaele | Tuminati, David | Ravaioli, Matteo | Fabbri, Carlo | Bacchi-Reggiani, Maria Letizia | Pession, Annalisa | Jovine, Elio | de Biase, Dario

Article Type: Research Article

Abstract: BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS , TP53 , SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery (“LS”) were analyzed for KRAS , TP53 , IDH1 , NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 …was tested using immunohistochemistry. MGMT promoter methylation was investigated. RESULTS: Tumors from “LS” have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. CONCLUSIONS: Our data indicate that absence of KRAS , TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome. Show more

Keywords: Pancreatic adenocarcinoma, KRAS, TP53, SMAD4, mutation

DOI: 10.3233/CBM-170464

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 323-334, 2018

Authors: Feng, Runhua | Sah, Birendra K. | Beeharry, Maneesh K. | Yuan, Fei | Su, Liping | Jin, Xiaolong | 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) by negatively regulating Crk protein expression post-transcriptionally. OBJECTIVE: The aim of this study was to investigate the associations of miR-126 and Crk protein expression levels, alone or in combination, with the clinicopathological characteristics and prognosis of GC patients. METHODS: The expression levels of miR-126 and Crk protein in 338 GC patients were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. The relationship of miR-126 and Crk protein expression with clinicopathologic characteristics and clinical outcome was evaluated. RESULTS: …Compared with matched adjacent non-tumor tissues, miR-126 was significantly down-regulated while Crk protein was significantly up-regulated in tumor tissues. A reduced miR-126 expression and an elevated Crk protein expression, alone or in combination, statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Multivariate analysis showed that combined miR-126-low/Crk protein-high expression was an independent unfavorable prognostic factor of GC. CONCLUSIONS: These results indicate for the first time that miR-126 down-regulation and Crk protein up-regulation may be synergistically associated with tumor progression in GC and may predict unfavorable prognosis of GC. Show more

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

DOI: 10.3233/CBM-170472

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 335-343, 2018