Cancer Biomarkers - Volume 20, issue 3

Authors: D’Andrea, Vito | Panarese, Alessandra | Tonda, Maya | Biffoni, Marco | Monti, Massimo

Article Type: Research Article

Abstract: According to the American Association of Cancer Research (AACR), a Cancer Stem Cell is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that constitutes the tumor [1 ]. Cancer Stem Cells (CSCs) are involved in the metastatic process, in the resistance to therapeutic treatments of many types of human cancers and consequently in the onset of recurrences. Numerous translational studies have been conducted to understand CSC characteristics and evaluate association between CSC-related biomarkers and clinical outcomes. The CSC theory can explain also a tumor relapse after that a tumor …has been completely surgically removed (R0 macroscopical zero residual resection) or after an apparently complete response to chemotherapy. CSCs, in fact, showed a marked ability to reduce intracellular accumulation of chemotherapic agents by active drug extrusion, increased chemoresistance and survival, as well as elevated membrane transporter activity. In addition, it is possible that these cancer stem cells may nest in the “secured” (niche) sites of our body, where they may remain undisturbed for a long time, even years, until a stimulus arrives to awaken them, causing the disease to resume. CSCs, in fact, are able to use a variety of cellular pathways to survive to anticancer treatments. More recently CSCs have been described in several solid tumors, expressing specific biomarkers. Another field of research should be focused on the realization of diagnostic instruments to follow up patients after R0 surgical resection or after a complete response for an early detection and management of relapse and metastasis. Show more

Keywords: Cancer stem cells, biomarkers, target therapy, niche

DOI: 10.3233/CBM-151176

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 231-234, 2017

Authors: Li, Peng | Liu, Ping | Zhang, Hui

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to evaluate the diagnostic value of ultrasound in thyroid Hürthle cell tumors. METHODS: A retrospective analysis was carried out on 27 patients with thyroid Hürthle cell tumors, in terms of the size, shape, boundary, echo, aspect ratio, cystic degeneration, calcification, peripheral halo sign and blood supply of the tumor, through surgical pathological validation. Then, these were compared with postoperative pathological results. RESULTS: The maximum diameter of the thyroid Hürthle cell tumors is between 0.6 cm and 4.6 cm. It had an oval nodule with clear boundaries, an aspect ratio …> 1, and peripheral low-echo halos. Furthermore, 29.6% of tumors have even low-echo nodules without cystic changes, 48.1% and 22.1% have even medium or medium-low mixed echo nodules, and 44.4% have cystic changes in varying degrees. One nodule appeared with “micro-calcification”, but pathological results confirmed that it was local collagen. Color Doppler blood flow imaging revealed that 88.8% of the nodules were surrounded with blood flow, filled with rich blood inside, and only 12.2% of the nodules had a little blood inside. CONCLUSION: Thyroid Hürthle cell tumors have nodules with even or uneven echoes on the background of the normal echoes of the thyroid, with an aspect ratio of > 1, clear boundaries and peripheral acoustic halos. Cystic changes, colloid crystallization and fibrosis can be seen inside in varying degrees. Ultrasonography has no significant value for the differential diagnosis of benign and malignant Hürthle cell tumors. Show more

Keywords: Hürthle cell neoplasm, papillary thyroid carcinoma, thyroid follicular neoplasm, ultrasonography

DOI: 10.3233/CBM-160544

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 235-240, 2017

Authors: Shi, Hongbin | Yu, Jianping | Li, Jie

Article Type: Research Article

Abstract: BACKGROUND: The nephroblastoma overexpressed gene (NOV) expressions in tissues and organs has become abnormal during tumorigenesis and progression. This study intended to investigate the correlation between clinical outcomes and NOV expression in renal cell carcinoma (RCC) patients. METHODS: Fifty RCC patients who attended the hospital from January 2013 to January 2015 were enrolled in this study. NOV expression in cancerous tissues and adjacent non-tumor (ANT) renal tissues of RCC patients was detected by immunohistochemistry (IHC). According to the percentage of NOV-positive cells, cases were divided into NOV-positive and NOV-negative groups. The correlations between age, gender, disease …course, tumor diameter, pathological grades (WHO/ISUP grading system) or tumor-node-metastasis (TNM) staging and NOV-positive rate were determined. Kaplan-Meier method was utilized for analyzing the 3- and 5-survial rates of RCC patients. The Cox proportional hazards regression model was used for the multivariate analysis. RESULTS: NOV-positive rate was uncorrelated with age, gender, disease course or TNM classification while was negatively correlated with pathological grades. NOV-positive rate in RCC tumor and ANT tissues was 58% and 100%, respectively. Five-year survival rate in NOV-positive group was significantly lower than that in NOV-negative group. CONCLUSION: Our data suggested that NOV down-regulation might be a biomarker for RCC but its positivity might be an indicator of poor prognosis. Show more

Keywords: Nephroblastoma overexpressed gene, renal clear cell carcinoma, immunohistochemistry, clinical outcome

DOI: 10.3233/CBM-170017

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 241-246, 2017

Authors: Zhao, Dahua | Zhang, Ying | Wang, Nana | Yu, Ning

Article Type: Research Article

Abstract: BACKGROUND: Studies have shown that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is related to breast cancer progression, however, the role of NEAT1 remains largely unknown. The aim of the current study was to further investigate the function of NEAT1 involved in breast cancer. METHODS: QRT-PCR was used to analyze lncRNA NEAT1 expression in breast cancer tissues and determine the association between NEAT1 and clinicopathologic features in patients. Kaplan-Meier analysis and the log-rank test were used to establish the relationship between NEAT1 and overall survival. Cell proliferation and invasion were evaluated based on CCK8 cell proliferation, cell …colony formation and Transwell cell invasion assays results. Bioinformatics analysis and the luciferase reporter assay were performed to demonstrate the association between NEAT1 and miR-218. RESULTS: NEAT1 expression was significantly up-regulated in breast cancer tissues compared to adjacent normal tissues, and higher NEAT1 was positively associated with lymph node metastasis and TNM stage. Patients with higher NEAT1 had a poor prognosis. Furthermore, miR-218 was shown to be a direct target of NEAT1 in breast cancer cells. In addition, NEAT1 promoted cell invasion and proliferation by negatively regulating miR-218 in breast cancer. CONCLUSION: NEAT1 is a potential biomarker for prognosis and the target of treatment in breast cancer patients. Show more

Keywords: NEAT1, miR-218, cell proliferation, cell invasion, prognosis

DOI: 10.3233/CBM-170027

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 247-254, 2017

Authors: Suwandittakul, Nantana | Reamtong, Onrapak | Molee, Pattamaporn | Maneewatchararangsri, Santi | Sutherat, Maleerat | Chaisri, Urai | Wongkham, Sopit | Adisakwattana, Poom

Article Type: Research Article

Abstract: BACKGROUND: Alterations and mutations of endo-lysosomal trafficking proteins have been associated with cancer progression. Identification and characterization of endo-lysosomal trafficking proteins in invasive cholangiocarcinoma (CCA) cells may benefit prognosis and drug design for CCA. OBJECTIVE: To identify and characterize endo-lysosomal trafficking proteins in invasive CCA. METHODS: A lysosomal-enriched fraction was isolated from a TNF-α induced invasive CCA cell line (KKU-100) and uninduced control cells and protein identification was performed with nano-LC MS/MS. Novel lysosomal proteins that were upregulated in invasive CCA cells were validated by real-time RT-PCR. We selected Rab7 for …further studies of protein level using western blotting and subcellular localization using immunofluorescence. The role of Rab7 in CCA invasion was determined by siRNA gene knockdown and matrigel transwell assay. RESULTS: Rab7 mRNA and protein were upregulated in invasive CCA cells compared with non-treated controls. Immunofluorescence studies demonstrated that Rab7 was expressed predominantly in invasive CCA cells and was localized in the cytoplasm and lysosomes. Suppression of Rab7 translation significantly inhibited TNF-α -induced cell invasion compared to non-treated control (p = 0.044). CONCLUSIONS: Overexpression of Rab7 in CCA cells was associated with cell invasion, supporting Rab7 as a novel candidate for the development of diagnostic and therapeutic strategies for CCA. Show more

Keywords: Cholangiocarcinoma, invasion, endo-lysosomal trafficking protein, Rab7

DOI: 10.3233/CBM-170030

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 255-266, 2017

Authors: Wang, Jing | Xie, Xin | Cheng, Feng | Zhou, Xin | Xia, Jun | Qian, Xifeng | Wang, Lingling | Guo, Hongfeng

Article Type: Research Article

Abstract: BACKGROUND: Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma (MM) has been less explored. OBJECTIVE: We aimed to investigate the association between RDW and the response to treatment and overall survival (OS) in patients with MM. METHODS: We retrospectively analyzed the data for 196 MM patients between January 1, 2007 and December 31, 2015. Kaplan-Meier analysis and Cox regression model were used. RESULTS: High …RDW values were associated with lower platelet count, lower hemoglobin levels, lower albumin levels, and higher lactate dehydrogenase (LDH) level. Among the entire cohort, the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy. The patients with low-RDW at diagnosis had better OS when compared to those with high-RDW. CONCLUSIONS: Elevated RDW was associated with worse survival in patients with MM and could predict treatment responses. Further larger and prospective studies are required. Show more

Keywords: Multiple myeloma, red cell distribution width, survival, prognostic

DOI: 10.3233/CBM-170032

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 267-272, 2017

Authors: Ogawa, Hiroomi | Kaira, Kyoichi | Takahashi, Kengo | Shimizu, Akira | Altan, Bolag | Yoshinari, Daisuke | Asao, Takayuki | Oyama, Tetsunari

Article Type: Research Article

Abstract: PURPOSE: The glucose-regulated protein 78 (GRP78), also referred to as immunoglobulin heavy chain binding protein (BiP) (BiP/GRP78), is a major molecular chaperone in the endoplasmic reticulum (ER) and is extensively expressed in human neoplasms. Although the enhanced expression of BiP/GRP78 has been described to be associated with poor prognosis in gastric cancer (GC), details regarding its prognostic significance remain unclear. The aim of this study was to elucidate the prognostic role of BiP/GRP78 in patients with GC. METHODS: Study subjects included 328 patients who underwent surgical resection. Tumor specimens of primary tumors underwent immunohistochemical staining for …BiP/GRP78. RESULTS: BiP/GRP78 was highly expressed in 57% (188/328) of patients. High expression of BiP/GRP78 was significantly associated with older age, male, disease staging, T factor, lymph node metastases, differentiation, lymphatic permeation, and vascular invasion. According to univariate analysis, age, disease staging, T factor, N factor, lymphatic permeation, vascular invasion, and BiP/GRP78 expression were significant prognostic factors for OS. In particular, high BiP/GRP78 expression was proven to be a significant predictor of prognosis in patients with older age, female sex, early disease stage, T1-2 factor, well or moderately differentiated tumors, and negative vascular invasion. CONCLUSION: BiP/GRP78 is significantly associated with tumor aggressiveness and progression. The increased expression of BiP/GRP78 was identified as an independent factor for predicting poor OS in patients with early stage of disease, especially T1-2 factor. Show more

Keywords: ER stress, BiP, GRP78, Gastric Cancer, prognosis, immunohistochemistry

DOI: 10.3233/CBM-170062

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 273-281, 2017

Authors: Wang, Kaichao | Dong, Liyuan | Fang, Qinmu | Xia, Hongwei | Hou, Xinlei

Article Type: Research Article

Abstract: BACKGROUND: Blood-circulating miRNAs have been reported to act as potential biomarkers in various cancers including non-small cell lung cancer (NSCLC). OBJECTIVE: This study was to assess serum miR-98 levels in NSCLC patients and explore its potential prognostic value. METHODS: The relative expression levels of miR-98 were detected by quantitative RT-PCR in the sera of 127 NSCLC patients and 60 healthy controls. RESULTS: Our results showed that serum miR-98 expression was down-regulated in NSCLC patients compared with healthy controls. Receiver operating characteristic (ROC) curve analysis suggested that serum miR-98 could be used …as a potential marker in the diagnosis of NSCLC. In addition, decreased serum miR-98 was positively correlated with worse TNM stage, lymph node metastasis, as well as unfavorable overall survival. Multivariate Cox regression analysis confirmed that serum miR-98 expression was an independent prognostic factor for NSCLC. CONCLUSIONS: Therefore, serum miR-98 might be useful as a promising biomarker for prognosis prediction of NSCLC. Show more

Keywords: Non-small cell lung cancer, serum miR-98, biomarker, diagnosis, prognosis

DOI: 10.3233/CBM-170124

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 283-288, 2017

Authors: Liu, De-Zhi | Zhao, Hui | Zou, Qin-Guang | Ma, Qing-Jie

Article Type: Research Article

Abstract: BACKGROUND: Previous studies indicated that microRNA-338-5p (miR-338-5p) functions as tumor suppressor in some cancer types including glioma. However, the clinical significance and biological function of miR-338-5p in glioma still need to be explored. METHODS: We used quantitative real time PCR (qRT-PCR) to detect the miR-338-5p expression in the 44 cases of glioma tissues and adjacent normal tissues. In vitro , CCK8 cell proliferation, cell colony formation, transwell invasion assay and flow cytometry analysis were performed to explore the effects of miR-338-5p on cell proliferation, cell invasion and cell cycle distribution. Dual luciferase assay, qRT-PCR and western …blot analysis were applied to validate CTBP2 was a direct target of miR-338-5p in glioma cells. RESULTS: we demonstrated that miR-338-5p was significantly lower expression in 44 glioma patients, compared with adjacent normal tissues. MiR-338-5p expression was significantly correlated with glioma grades and Karnofsky Performance Status in patients. We then validated that increased miR-338-5p significantly inhibited the cell proliferation, cell invasion and epithelial-mesenchymal transition (EMT) in vitro . Moreover, Dual luciferase assay results indicated that CTBP2 was direct target of miR-338-5p in glioma cells. Meanwhile, CTBP2 silencing can rescued the phenotype changes induced by miR-338-5p inhibitor on cell proliferation and invasion in glioma. CONCLUSION: Our results suggested that miR-338-5p acts as tumor suppressor and could be a potential therapeutic target for glioma. Show more

Keywords: Glioma, miR-338-5p, CTBP2, cell proliferation, cell invasion

DOI: 10.3233/CBM-170128

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 289-297, 2017

Authors: Giamanco, Nicole M. | Jee, Youn Hee | Wellstein, Anton | Shriver, Craig D. | Summers, Thomas A. | Baron, Jeffrey

Article Type: Research Article

Abstract: BACKGROUND/OBJECTIVE: Midkine (MDK) and pleiotrophin (PTN) are two closely related heparin-binding growth factors which are overexpressed in a wide variety of human cancers. We hypothesized that the concentrations of these factors in washout of biopsy needles would be higher in breast and lung cancer than in benign lesions. METHODS: Seventy subjects underwent pre-operative core needle biopsies of 78 breast masses (16 malignancies). In 11 subjects, fine needle aspiration was performed ex vivo on 7 non-small cell lung cancers and 11 normal lung specimens within surgically excised lung tissue. The biopsy needle was washed with buffer …for immunoassay. RESULTS: The MDK/DNA and the PTN/DNA ratio in most of the malignant breast masses were similar to the ratios in benign masses except one lobular carcinoma in situ (24-fold higher PTN/DNA ratio than the average benign mass). The MDK/DNA and PTN/DNA ratio were similar in most malignant and normal lung tissue except one squamous cell carcinoma (38-fold higher MDK/DNA ratio than the average of normal lung tissue). CONCLUSIONS: Both MDK and PTN are readily measurable in washout of needle biopsy samples from breast and lung masses and levels are highly elevated only in a specific subset of these malignancies. Show more

Keywords: Midkine, pleiotrophin, needle biopsy, breast mass, lung mass

DOI: 10.3233/CBM-170145

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 299-307, 2017