Cancer Biomarkers - Volume 24, issue 1

Authors: Mo, Ha Yoon | Jo, Yun Sol | Yoo, Nam Jin | Kim, Min Sung | Song, Sang Yong | Lee, Sug Hyung

Article Type: Research Article

Abstract: BACKGROUND: Both QKI and TMEFF2 genes are considered putative tumor suppressor genes (TSGs). In gastric (GC) and colorectal (CRC) cancers, downregulation of their expressions is known to be frequent. However, QKI and TMEFF2 mutations that could potentially inactivate their functions are not reported in cancers. METHODS: In a genome database, we observed that both QKI and TMEFF2 harbor mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we studied 79 GCs and 124 CRCs for the mutations and their intratumoral heterogeneity (ITH). RESULTS: Six of 34 GCs …(17.6%) and 10 of 79 CRCs (12.7%) with MSI-H exhibited QKI frameshift mutations while five of 79 CRCs (6.3%) with high MSI (MSI-H) exhibited TMEFF2 frameshift mutations. However, we found no such mutation in microsatellite stable/low MSI (MSS/MSI-L) cancers within the mononucleotide repeats. We also studied ITH for the detected frameshift mutations in 16 cases of CRCs and detected that QKI and TMEFF2 frameshift mutations showed regional ITH in 2 (12.5%) and 1 (6.3%) cases, respectively. CONCLUSIONS: Our data show that candidate TSG genes QKI and TMEFF2 harbor mutational ITH as well as the frameshift mutations in GC and CRC with MSI-H. From this observation, frameshift mutations of QKI and TMEFF2 may play a role in tumorigenesis through their TSG inactivation in GC and CRC. Show more

Keywords: QK1, TMEFF2, tumor suppressor gene, methylation, frameshift mutation, cancer, microsatellite instability

DOI: 10.3233/CBM-160559

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 1-6, 2019

Authors: Zhang, Nan | Cong, Xiaoqiang | Zhou, Dan | Guo, Liang | Yuan, Congwang | Xu, Dahai | Su, Chang

Article Type: Research Article

Abstract: BACKGROUND: The significance of serum dipeptidyl peptidase-IV (DPP-IV) in papillary thyroid carcinoma (PTC) has not been elucidated. OBJECTIVE: This study aimed to assess the role of serum DPP-IV in the carcinogenesis and prognosis of PTC. METHODS: The serum DPP-IV concentration was measured in 171 male patients with PTC, 81 male patients with a benign thyroid nodule (BTN), and 52 male healthy controls (HCs). Multivariate logistic regression and Cox regression analyses were performed to evaluate the correlations between variables. Receiver operating characteristic (ROC) curves were used to calculate the diagnosis accuracy. RESULTS: …The ROC curve indicated a good performance of DPP-IV for discriminating PTC from BTN, with an area under the curve (AUC) of 0.881 (95% CI, 0.840–0.922). Serum DPP-IV demonstrated a modest performance in predicting nonstructurally persistent disease/recurrent disease (NSPRD) survival, with an AUC of 0.778 (95% CI, 0.635–0.922). A serum DPP-IV level ⩾ 250 nkat/L (HR, 6.529; 95% CI, 2.090–20.398; P = 0.001) and an advanced tumor, lymph node, metastasis (TNM) stage (HR, 4.677; 95% CI, 1.498–14.605; P = 0.008) were found to be independent factors for predicting SPRD. PTC patients with a DPP-IV level ⩾ 250 nkat/L had a worse outcome than those with a DPP-IV level < 250 nkat/L (P < 0.001). CONCLUSIONS: Serum DPP-IV may be a predictive biomarker for PTC diagnosis and prognosis in Chinese male patients. Show more

Keywords: Dipeptidyl peptidase-IV, CD26, papillary thyroid carcinoma, structurally persistent, recurrent disease

DOI: 10.3233/CBM-170908

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 7-17, 2019

Authors: Ries, Jutta | Baran, Christoph | Wehrhan, Falk | Weber, Manuel | Motel, Constantin | Kesting, Marco | Nkenke, Emeka

Article Type: Research Article

Abstract: BACKGROUND: Altered expressions of miR-186, miR-494 and miR-3651 in whole blood of OSCC patients have already been demonstrated. However, nothing is known about their expression in tumor tissues. This study aimed at evaluating differences in miRNA expression in OSCC tissues compared to healthy oral mucosa and at checking if the altered expression is reflected in corresponding blood. METHODS: In 53 OSCC and 40 healthy mucosal tissues the expression of miR-186, -494 and -3651 was determined by RT-qPCR and expression levels were compared between the groups. The altered expression in tissues was compared with that determined for …corresponding blood. MiR-3651 target genes were identified using TargetScan software. RESULTS: Differential expression of miR-186 and miR-494 could not be observed in tumor tissues compared to normal mucosa (p miR-186 = 0.13; p miR-494 = 0.35). Contrary to the detected upregulation of the miR-3651 in the blood of OSCC patients, a significant downregulation was observed in OSCC tissues. A significant correlation between underexpression and diagnosis was ascertained (p = 0.0001). 1710 possible target genes of miR-3651 were identified. CONCLUSIONS: Decreased expression of miR-3651 in OSCC tissues may be a diagnostic biomarker. The opposite change in expression level in the blood might indicate different functions of this miRNA in circulation and tissue. Show more

Keywords: Oral squamous cell carcinoma, whole peripheral blood, tumor tissue, miRNA expression, RT-qPCR

DOI: 10.3233/CBM-180032

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 19-30, 2019

Authors: Zhang, Li-Ya | Chen, Yuan | Jia, Jue | Zhu, Xi | He, Yan | Wu, Li-Ming

Article Type: Research Article

Abstract: BACKGROUND: Ovarian cancer (OC) is the fifth most common type of cancer in women worldwide. MiR-27a plays an important role in the development of ovarian cancer. However, the exact function and molecular mechanism of miR-27a in epithelial-mesenchymal transition (EMT) has not been thoroughly elucidated to date. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of miR-27a and FOXO1 mRNA in ovarian tissues and cells. The function of miR-27a in ovarian cancer was investigated through overexpression and knockdown of miR-27a in vitro. Wound healing and Transwell assays were performed to evaluate the migration and …invasive capacity of the cells. A luciferase reporter assay was conducted to confirm the interaction between miR-27a and FOXO1. Western blotting was used to evaluate FOXO1, EMT and Wnt/β -catenin relative protein expression. RESULTS: In our study, we found that the mRNA expression level of miR-27a was significantly higher in ovarian cancer tissues and in HO8910 and OV90 cells. Functional experiments showed that miR-27a overexpression potentiated the migration and invasion of HO8910 and OV90 cells, while miR-27a inhibition reduced the cells’ migration and invasion. Moreover, miR-27a upregulated the expression of mesenchymal cell markers and downregulated the expression of epithelial cell markers, which were restored via silencing of miR-27a expression. Subsequently, miR-27a was found to directly target and suppress the expression of FOXO1. Finally, we demonstrated that miR-27a promoted the progression of ovarian cancer cells and induced the process of EMT via the Wnt/β -catenin signalling pathway through inhibition of FOXO1. CONCLUSIONS: Taken together, these results indicate that targeting miR-27a and FOXO1 could represent a strategy for anticancer therapy in ovarian cancer. Show more

Keywords: Ovarian cancer, microRNA-27a, FOXO1, EMT, Wnt/β-catenin

DOI: 10.3233/CBM-181229

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 31-42, 2019

Authors: Zhang, Huiping | Wang, Jianfeng | Wang, Zhanying | Ruan, Cailian | Wang, Lu | Guo, Hongtao

Article Type: Research Article

Abstract: BACKGROUND: It is well known that some circulating microRNAs (miRNAs) are highly stable and might serve as promising biomarkers for many types of human cancer including glioblastoma (GBM). However, the potential clinical significance of serum miR-100 in GBM remained unknown. OBJECTIVE: We aimed to detect the expression level of serum miR-100 in patients with GBM and assess its potential diagnostic and prognostic value. METHODS: Quantitative real-time PCR was performed to measure serum miR-100 levels in 95 GBM patients and 60 healthy volunteers. The association between serum miR-100 level and clinicopathological parameters as well …survival of GBM patients was evaluated. RESULTS: Our results revealed that serum miR-100 levels were significantly decreased in GBM patients compared with the healthy controls. Additionally, miR-100 levels were significantly elevated after treatment. Low miR-100 expression was closely correlated with worse clinicopathological characteristics. Further receiver operating characteristic (ROC) curve analysis showed that serum miR-100 could effectively discriminate GBM cases from normal controls. Moreover, survival analyses revealed that patients with high serum miR-100 levels had significantly longer survival time than those with low serum miR-100 levels. Finally, multivariate analysis identified serum miR-100 as an independent prognostic indicator for GBM. CONCLUSIONS: Our findings suggested that serum miR-100 might serve as promising biomarker for GBM diagnosis and prognosis. Show more

Keywords: Glioblastoma, serum miR-100, prognosis, biomarker

DOI: 10.3233/CBM-181416

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 43-49, 2019

Authors: Li, Hong | Wang, Huogang | Deng, Ke | Han, Wei | Hong, Bo | Lin, Wenchu

Article Type: Short Communication

Abstract: BACKGROUND: Cisplatin-based chemotherapy and radiotherapy are the most commonly used treatments for small cell lung cancer (SCLC). However, despise initially dramatic response, the response duration of SCLC patients is variable and resistance to chemo- and radio-therapy inevitably develops. OBJECTIVE: The aim of the study is to investigate the role of Bcl-2 family proteins in predicting SCLC sensitivity to cisplatin treatment, and to identify the potential sensitizer of cisplatin or ratiation treatment in SCLC. METHODS: We collected cisplatin sensitivity data from public available database, and evaluated its possible association with mRNA or protein expression …of Bcl-2 family members in SCLC cell lines. RESULTS: The IC 50 value of cisplatin was significantly correlated with the ratio of Bcl-2/Bim mRNA expression in 33 SCLC cell lines (P = 0.041) as well as the ratio of Bcl-2/Bim protein expression in 7 SCLC cell lines (P = 0.0252). Furthermore, a BH3-mimetic ABT-263 was found to be able to sensitize SCLC cells to cisplatin or radiation. The synergistic and additive antitumor activity of ABT-263 combined with cisplatin or radiation was associated with the enhanced apoptosis, which may be caused by the disruption of Bcl-2 binding to Bim by ABT-263. CONCLUSIONS: Our study indicates that the ratio of Bcl-2/Bim could be a SCLC response predictor to cisplatin, and ABT-263 addition could be an effective strategy to improve the activity of chemo- or radio-therapy in SCLC. Show more

Keywords: Small cell lung cancer, Bcl-2, Bim, ABT-263, cisplatin, radiation

DOI: 10.3233/CBM-181692

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 51-59, 2019

Authors: Wu, Yibin | Fang, Guojiu | Wang, Xin | Wang, Huipeng | Chen, Wenjie | Li, Liang | Ye, Tao | Gong, Lifeng | Ke, Chongwei | Cai, Yuankun

Article Type: Research Article

Abstract: BACKGROUND : Nucleoporin NUP153 (NUP153) is well known to be involved in the regulating of nuclear transport. Although NUP153 is associated with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. OBJECTIVE: The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation. METHODS: The expression levels of NUP153 in CRC tissues and matched normal colon tissues were examined by real-time quantitative PCR and immunohistochemistry. Then the association between NUP153 levels with clinical variables as well …as survival time was investigated. Moreover, overexpression of NUP153 in HCT116 cells was established to study its influence on cell proliferation in vitro , and a xenograft model was performed to explore this effect in vivo . RESULTS: We found that NUP153 was highly expressed in adjacent normal tissues than in cancer tissues, and elevated NUP153 expression was negatively associated with pathological grade (P = 0.015), T stage (P = 0.048) and distant metastasis (P = 0.006). Kaplan-Meier analysis revealed that patients with higher NUP153 expression had a longer overall survival (OS) (P = 0.01) and recurrence free disease (RFS) (P = 0.001). Logistic regression analysis further identified NUP153 as an independent prognostic safe factor for OS and recurrence. Moreover, NUP153 overexpression suppressed CRC cells proliferation and inhibited tumor growth in a xenograft model. Its mechanistic investigations showed that NUP153 overexpression inhibited β -catenin transcriptional activity and down-regulated the mRNA expression levels of Wnt downstream proteins-Axin2, cyclinD1, c-myc and lef-1. CONCLUSIONS: NUP153 might be a promising prognostic factor, a potential tumor suppressor and therapeutic target in human CRC through an interaction with the Wnt/β -catenin signaling pathway. Show more

Keywords: NUP153, colorectal cancer, suppressor gene, prognosis, proliferation, Wnt/β-catenin pathway

DOI: 10.3233/CBM-181703

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 61-70, 2019

Authors: Reyes, Ismael | Reyes, Niradiz | Suriano, Robert | Iacob, Codrin | Suslina, Nina | Policastro, Anthony | Moscatello, Augustine | Schantz, Stimson | Tiwari, Raj K. | Geliebter, Jan

Article Type: Research Article

Abstract: BACKGROUND: Thyroid cancer is the most common endocrine malignancy worldwide, with the predominant form papillary thyroid carcinoma (PTC) representing approximately 80% of cases. OBJECTIVE: This study was addressed to identify potential genes and pathways involved in the pathogenesis of PTC and potential novel biomarkers for this disease. METHODS: Gene expression profiling was carried out by DNA microarray technology. Validation of microarray data by qRT-PCR, western blot, and enzyme linked immunosorbent assay was also performed in a selected set of genes and gene products, with the potential to be used as diagnostic or prognostic …biomarkers, such as those associated with cell adhesion, extracellular matrix (ECM) remodeling and immune/inflammatory response. RESULTS: In this study we found that upregulation of extracellular activities, such as proteoglycans, ECM-receptor interaction, and cell adhesion molecules, were the most prominent feature of PTC. Significantly over-expressed genes included SDC1 (syndecan 1), SDC4 (syndecan 4), KLK7 (kallikrein-related peptidase 7), KLK10 (kallikrein-related peptidase 10), SLPI (secretory leukocyte peptidase inhibitor), GDF15 (growth/differentiation factor-15), ALOX5 (arachidonate 5-lipoxygenase), SFRP2 (secreted Frizzled-related protein 2), among others. Further, elevated KLK10 levels were detected in patients with PTC. Many of these genes belong to KEGG pathway “Proteoglycans in cancer”. CONCLUSIONS: Using DNA microarray analysis allowed the identification of genes and pathways with known important roles in malignant transformation, and also the discovery of novel genes that may be potential biomarkers for PTC. Show more

Keywords: Biological Markers, gene expression, kallikrein-related peptidase, thyroid carcinoma

DOI: 10.3233/CBM-181758

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 71-83, 2019

Authors: Ma, Baofeng | Liu, Xiaoming | Yu, Zhaoxiao

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the effects of high intensity focused ultrasound on liver function, tumor markers and survival rate of hepatocellular carcinoma patients. METHODS : Ninety six cases with primary liver cancer patients, consisting of 66 males and 30 females, were enrolled in this study and treated with high intensity focused ultrasound combined with stereotactic segmentation dose radiation, low frequency for 10 times, followed by analysis of KPS score of liver cancer, Child-Pugh, grading and staging of liver cancer, 3 months, 6 months, 1 year of clinical symptom remission rate, tumor markers, liver function, survival rate, as well as the change of immune related …cytokines. RESULTS: Three months after high intensity focused ultrasound treatment, abdominal distension abdominal pain, jaundice symptoms, anorexia and ascites were significantly relieved compared with before treatment (P < 0.05). At 3 months after treatment, levels of AFP and CA199 were significantly reduced than before treatment (P < 0.05). Meanwhile, Child-Pugh classification score was significantly decreased at 3 months after treatment compared with before treatment, which was further decreased at 6 months after treatment than 3 months after treatment (P < 0.05). In addition, ALT, AST, AKP, propagated and TBIL level at 3 months after treatment displayed no differences to those before treatment but was significantly decreased at 6 months treatment (P < 0.05). Moreover, the late stages of liver cancer, the lower survival rate after treatment. Furthermore, the levels of NK, CD3, CD4, CD8 and CD4/CD8 cytokines were significantly increased at 3 months after treatment (P < 0.05), together with significantly increased levels of IFN-r and IL-2 and decreased levels of IL-4 and IL-10 (P < 0.05). CONCLUSION: High intensity focused ultrasound can effectively improve liver function, increase the survival rate and enhance immune function of patients with liver cancer. Show more

Keywords: Ultrasonic treatment, liver cancer, curative effect, immunizing

DOI: 10.3233/CBM-181822

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 85-90, 2019

Authors: Nomura, Megumi | Matsumoto, Kazumasa | Shimizu, Yuriko | Ikeda, Masaomi | Amano, Noriyuki | Nishi, Mayuko | Ryo, Akihide | Nagashio, Ryo | Sato, Yuichi | Iwamura, Masatsugu

Article Type: Research Article

Abstract: BACKGROUND: New biomarkers may help us provide individualized prognosis and allow risk-stratified clinical decision making about radical treatment. OBJECTIVES: This study aimed to determine the tumor necrosis factor of receptor superfamily 19 (TROY) expression in urothelial carcinoma and its relationship to clinicopathological findings. METHODS: Immunohistochemical staining for TROY was carried out in 136 archival radical cystectomy specimens with immunoreactivity being stratified on a 0–9 scale. Expression scores for TROY were further stratified into negative (score 0) and positive (score 1 or greater). Median age was 65 years, and the median follow-up period was …50.7 months. RESULTS: Expression of TROY was significantly associated with the pathological stage (p = 0.019) and expression of nestin (p = 0.013). Log-rank tests indicated that expression of TROY was significantly associated with disease progression and cancer-specific mortality (p = 0.044 and 0.008, respectively). In multivariate Cox regression analysis, lymph node status was the only independent prognostic factor for disease progression and cancer-specific survival. Expression of TROY was a marginal prognostic factor for cancer-specific survival. CONCLUSIONS: TROY may therefore be a new molecular marker to aid in identifying and selecting patients undergoing radical cystectomy who could potentially benefit from multimodal treatment. Show more

Keywords: Bladder cancer, cystectomy, nestin, urothelial carcinoma, TROY

DOI: 10.3233/CBM-181911

Citation: Cancer Biomarkers, vol. 24, no. 1, pp. 91-96, 2019