Cancer Biomarkers - Volume 23, issue 3

Authors: Lv, Tu | Liu, Youyu | Li, Zihuan | Huang, Ruoqiang | Zhang, Zhaoyi | Li, Jianjun

Article Type: Research Article

Abstract: We analyzed the expression of miR-503 in osteosarcoma tissues (OS) and discussed the clinical significance of our findings. To provide a theoretical basis for clinical applications, prognosis prediction and treatment of osteosarcoma, we studied the biological function of miR-503 and its mechanism in MG63 osteosarcoma cells. Real-time polymerase chain reaction (PCR) was used to detect the expression of miR-503 in 45 OS tissues and 20 osteochondroma tumors, analyzing the relationship between clinical pathology and follow-up data. Cox multivariate analysis revealed the clinical and pathological features of the osteosarcoma index and the influence of miR-503 expression on OS prognosis. To observe the effect …on cell proliferation and invasion, MG-63 cells were transfected with miR-503. The TargetScan and PicTar bioinformatics method was used to analyze the probable target gene of miR-503 and, combined with the function of the target genes, resulted in a final validation of related pathways. miR-503 was significantly down-regulated in primary OS samples (26/45, 57.8%). The median miR-503 expression level in osteosarcoma was two-fold lower than that in osteochondroma (median expression 6.4 and 13.09, respectively, P < 0.05). The less-expressed miR-503 was associated with Enneking stage (p = 0.004) and invasion (p = 0.015) of OC. Patients with low miR-503 expression had poorer overall survival time. In the multivariate analysis, miR-503 was a significant prognostic factor (P = 0.010). miR-503 can inhibit proliferation and invasion in the MG63 cell line. Using bioinformatics, VEGFA and Rictor were determined to be the likely downstream target genes of miR-503. VEGFA, Rictor, Akt and Erk1/2 were negatively regulated by the overexpression of miR-503. In conclusion, miR-503 has significant tumor-suppressor biological activity and is thus likely to become a new target for the treatment of osteosarcoma. Show more

Keywords: Osteosarcoma, miR-503, prognosis, VEGFA, Rictor

DOI: 10.3233/CBM-170906

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 315-322, 2018

Authors: Chen, Guan-Yu | Zheng, Hua-Chuan

Article Type: Research Article

Abstract: BACKGROUND: Dkk3 protein attenuates the expression of Wnt3a, Wnt5a and LRP6, and their interaction, and interacts with β TrCP to suppress wnt/β -catenin pathway. METHODS: We performed a bioinformatics analysis of Dkk3 mRNA expression through Oncomine, TCGA and Kaplan-Meier plotter databases up to July 10, 2017. RESULTS: Up-regulated Dkk3 expression was higher in gastric, breast, and ovarian cancers than normal tissues (p < 0.05). Bitter’s database showed a higher Dkk3 expression in ovarian cytoadenocarcinoma than clear cell adenocarcinoma (p < …0.05). Dkk3 was more expressed in ductal breast cancer in situ than invasive ductal breast cancer (p < 0.05), in mixed lobular and ductal cancer, and lobular cancer than ductal breast cancer (p < 0.05). In TCGA data, Dkk3 expression was lower in gastric cancers with than without Barret’s esophagus (p < 0.05), in intestinal-type than diffuse-type cancers (p < 0.05), and in the cancers of elder than younger patients (p < 0.05). Dkk3 expression was higher in squamous cell carcinoma than adenocarcinoma (p < 0.05). Dkk3 expression was higher in ductal than lobular breast cancer, or in younger than elder patients with breast cancer (p < 0.05). According to Kaplan-Meier plotter, Dkk3 expression was negatively correlated with overall, progression-free, relapse-free or distant-metastasis-free survival rate of gastric, breast or ovarian cancer patients, but versa for lung cancer patients (p < 0.05). CONCLUSION: Dkk3 expression might be employed as a potential marker to indicate carcinogenesis and histogenesis, even prognosis. Show more

Keywords: Dkk3, carcinogenesis, aggressiveness, prognosis, bioinformatics analysis

DOI: 10.3233/CBM-181245

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 323-331, 2018

Authors: Chen, Liang | Hu, Jing | Pan, Lina | Yin, Xiaochun | Wang, Qibao | Chen, Hui

Article Type: Research Article

Abstract: BACKGROUND: Despite progress in the treatment of oral squamous cell carcinoma (OSCC) over past years, the prognosis for OSCC patients remains dismal. MicroRNA-99a (miR-99a) has been found to involve in the development of many cancer types, but its clinical role in OSCC is unclear. OBJECTIVE: The aim of this study was to explore the clinical implications of serum miR-99a in OSCC. METHODS: This study detected serum miR-99a levels in 121 OSCC cases and 55 healthy controls by using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: The data showed that serum …miR-99a expression was significantly decreased in OSCC patients compared with normal controls. OSCC patients with low miR-99a expression experienced more frequent poor differentiation and advanced clinical stage. Furthermore, in screening OSCC cases from normal controls, miR-99a could yield a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.911 with 83.6% specificity and 80.2% sensitivity. Notably, patients with high miR-99a expression had longer overall survival and recurrence free survival. Finally, serum miR-99a was identified to be an independent prognostic indicator for OSCC. CONCLUSIONS: These results suggested that miR-99a might be a valuable marker for the prediction of early detection and prognosis in OSCC. Show more

Keywords: Oral squamous cell carcinoma, serum miR-99a, prognosis, diagnosis, biomarker

DOI: 10.3233/CBM-181265

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 333-339, 2018

Authors: Li, Na | Jilisihan, Bulibu | Wang, Wei | Tang, Yong | Keyoumu, Saifuding

Article Type: Research Article

Abstract: OBJECTIVE: Gastric cancer (GC) is the second most common lethal cancer worldwide and lymphocyte-activation gene 3 (LAG3) as a therapeutic target for cancers has been investigated. Herein, our study is to clarify the value of peripheral blood (PB) soluble LAG-3 (sLAG3) in GC. METHODS: Peripheral serum samples of GC patients and healthy people were collected for the measurement of serum levels of sLAG3, carcinoembryonic antigen (CEA), IL-12 and IFN-γ . Additionally, ROC and Kaplan-Meier curves were adopted to identify the diagnostic and prognostic values of sLAG-3 in patients with GC. Then, GC-bearing mice were …treated with recombinant sLAG3. The tumor volume was measured, and CD8 + T cell frequency was detected in PB and tumor-ininfiltrating area. Additionally, the expression of IL-12 and IFN-γ in T cells was assayed and the overall survival of mice was analyzed. RESULTS: sLAG3 in PB was poorly expressed and its expression was positively correlated with IL-12 and IFN-γ expression in GC patients. sLAG3 was proved to have a higher diagnostic value than CEA in GC. Moreover, high sLAG-3 expression is found in relation to a better prognosis in GC. The in vivo experiments indicated that sLAG-3 might inhibit the tumor growth, and promote the secretion of CD8 + T cells, IL-12 and IFN-γ . Furthermore, sLAG-3 was able to prolong overall survival and increase survival rate of GC-bearing mice. CONCLUSION: Based on these findings, we conclude that sLAG3 positively regulates CD8 + T cells, IL-12 and IFN-γ , and function as a prognostic marker for GC, which might be a potential target in the treatment of GC. Show more

Keywords: LAG3, CD8+T cells, gastric cancer, tumor immunity, survival

DOI: 10.3233/CBM-181278

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 341-351, 2018

Authors: Meng, Fu-Tao | Huang, Mei | Shao, Feng | Huang, Qiang

Article Type: Research Article

Abstract: BACKGROUND: Free fatty acid receptor 4 (FFAR4) is associated with the epithelial mesenchymal transition (EMT) and is involved in the progression of several types of cancer. However, the role of FFAR4 in cholangiocarcinoma (CCA) remains unclear. OBJECTIVE: The present study evaluated the diagnosis and prognosis of CCA using FFAR4 as a biomarker. METHODS: Immunohistochemistry was employed to detect expression of FFAR4 in 98 samples of CCA tissues and adjacent tissues. In addition, expression of E-cadherin, vimentin, Snail-1, CK7 and CK19 in the 98 samples of CCA tissues was detected, and relationships with FFAR4 were analyzed. …Correlation between FFAR4 and clinical pathological factors and prognosis was also analyzed. RESULTS: FFAR4 was highly expressed in 72.4% (71/98) of CCA tissues and 29.6% (29/98) of adjacent tissues, with a statistically significant difference between the two tissue types (P < 0.05). A negative correlation between high expression FFAR4 and E-cadherin expression in CCA tissues was also observed (r = - 0.445, P < 0.001), and high expression of FFAR4 was positively correlated with vimentin (r = 0.354, P < 0.001), Snail-1(r = 0.496, P < 0.001), CK7(r = 0.494, P < 0.001) and CK19 (r = 0.532, P < 0.001). Moreover, the degree of FFAR4 expression was associated with aggressive clinicopathological characteristics, such as histological grade, perineural invasion (PNI), lymph node metastasis (LNM), advanced TNM stage and preoperative serum CA19-9 level (P < 0.05). In terms of prognosis, CCA patients with high FFAR4 expression showed shorter disease-free survival (DFS) (P < 0.05) and overall survival (OS) (P < 0.05) than did patients with low FFAR4 expression. CONCLUSIONS: FFAR4 overexpression may mediate the process of CCA EMT. In addition, FFAR4 is promising as a new diagnostic molecule and therapeutic target for CCA. Show more

Keywords: Immunohistochemistry, FFAR4, cytokeratin7, cytokeratin19, E-cadherin, vimentin, Snail-1, prognosis

DOI: 10.3233/CBM-181358

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 353-361, 2018

Authors: Li, Xun | Liu, Jie | Shi, Peng-Fei | Fu, Peng

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study was to investigate the correlation of katanin P80 expression with clinicopathological features and overall survival (OS) in surgical breast cancer (BC) patients. METHODS: Four hundred and fourteen BC patients underwent surgery were analyzed in this retrospective cohort study. Katanin P80 expression was examined by immunofluorescence assay. The median follow-up duration was 118.0 months (quantiles: 99.0–140.5 months), the last follow-up date was Jul 1st 2017. RESULTS: Eighty-five patients (20.5%) with katanin P80 positive expression and 329 patients (79.5%) with katanin P80 negative expression were observed in this research. Katanin P80 …positive expression was correlated with higher N stage (p < 0.001) and TNM stage (p < 0.001). K-M curve and log-rank test revealed that katanin P80 positive patients presented with shorter OS compared with katanin P80 negative patients (p < 0.001). Multivariate Cox’s regression analysis disclosed that katanin P80 positive expression (p < 0.001) and histologic grade (p < 0.001) could independently predict unfavorable OS. Furthermore, subgroups analysis was performed, which illuminated that katanin P80 positive expression was correlated with shorter OS in all subgroups divided by molecular subtyping and TNM stage (all p < 0.05) except in TNM stage I subgroup (p = 0.573). CONCLUSION: Katanin P80 expression positively correlated with lymph node metastasis and could abe a novel biomarker for prognosis in BC patients. Show more

Keywords: Katanin P80, breast cancer, lymph node metastasis, prognostic factor, overall survival

DOI: 10.3233/CBM-181369

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 363-371, 2018

Authors: Andleeb, Farah | Hafeezullah, | Atiq, Atia | Atiq, Maria | Malik, Sadia

Article Type: Research Article

Abstract: Early diagnosing of skin cancer and investigation of metastatic potential of cancer cells are very important to treat it appropriately. Infrared spectroscopy of biological tissues is an emerging technique which gives the spectral differences between healthy and diseased cells. In this work, we have demonstrated that attenuated total reflectance Fourier transform (ATR-FTIR) spectroscopy can be used in diagnostic of skin cancer and in differentiating metastatic potential of cancer cells. Using IR spectroscopy, we can identify various types of cancer such as basal cell carcinoma, malignant melanoma, nevus and metastatic potential by alternations in hydration level and molecular changes. We examined …biopsy of different types of cancer cells to diagnose skin cancer at early stages by using FTIR spectroscopy. To differentiate metastases we examined two human melanoma cells of same patient but at different metastatic potential and two murine melanoma cells with common genetic background but different metastatic potential. Our findings revealed that melanoma changes the permeability of cell membrane and higher metastatic potential is related to the hydration level of cell membrane. Thus, ATR-FTIR spectroscopy is a potential technique to help in early diagnosing of skin cancer and to differentiate different metastatic potentials. Show more

Keywords: Metastatic, ATR-FTIR, melanoma, spectroscopy

DOI: 10.3233/CBM-181393

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 373-380, 2018

Authors: Liang, Jun | Zhang, Xian-Li | Li, Shun | Xie, Shao | Wang, Wei-Feng | Yu, Ru-Tong

Article Type: Research Article

Abstract: Ubiquitin-specific protease 22 (USP22), as one of the 11 death-from-cancer signature genes, presented high expression in a variety of tumors. Previous studies showed that USP22 played a significant role in cell-cycle, oncogenesis, clinicopathology and survival. Our studies have presented USP22 was over-expressed in glioma tissue and the patients with high expression of USP22 had a poor survival than that with low expression of USP22. However, the concrete effect of USP22 on biological behavior in glioma cells has been rarely reported. The study aimed to clear the effect of USP22 on cell proliferation, migration and invasion in glioma. Using siRNA, USP22 was …knocked down in U251 and U87 glioma cells and successful transfection effect was validated. Cell proliferation, migration and invasion were observed by the methods of EdU, Wound healing and Transwell assay, separately. At the same time, the expression of MMP2 was detected by Gelatin zymography after transfecting siRNAs. After the knockdown of USP22 by siRNA, the abilities of glioma cell proliferation, migration and invasion were decreased, accompanying, the expression of MMP2 was also decreased. We drew a conclusion that USP22 could increase the abilities of proliferation, migration and invasion of glioma cells, and promote the growth and development of glioma. Show more

Keywords: Ubiquitin-specific protease 22 (USP22), glioma cell, proliferation, migration, invasion

DOI: 10.3233/CBM-181413

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 381-389, 2018

Authors: Abdelrahman, Aziza E. | Ibrahim, Hanaa M. | Elsebai, Eman A. | Ismail, Eman I. | Elmesallamy, Wael

Article Type: Research Article

Abstract: BACKGROUND: The treatment strategies of astrocytoma have not changed considerably due to the restricted appreciation of its biology. OBJECTIVES: This study aimed to evaluate the expression of the stem cell-related proteins (CD133 and Sox2) and their prognostic value in astrocytic glioma. METHODS: The immunohistochemical expression of CD133 and Sox2 in 40 patients with an astrocytic glioma of different grades was studied. The recorded data on the overall survival (OS), progression-free survival (PFS) and the response to the therapeutic protocol were collected and lastly analyzed. RESULTS: CD133 expression was observed in 87.5% …of the cases, while positive Sox2 expression was found in all the studied cases. There was a significant association of CD133 expression with the histological grade and the tumor size (p < 0.001). A significant association of Sox2 with the histological grade and the tumor size was noted (p = 0.004, p = 0.006 respectively). Up-regulation of both CD133 and Sox2 had a significant association with poor clinical response to the therapy (p < 0.001 for each). Shorter OS and PFS were related to CD133 and Sox2 overexpression. CONCLUSIONS : Astrocytoma with CD133 and Sox2 overexpression had an unfavorable prognosis and poor clinical response to the current therapeutic protocol. Show more

Keywords: CD133, Sox2, astrocytoma, immunohistochemistry

DOI: 10.3233/CBM-181460

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 391-403, 2018

Authors: Fang, Ying | Yuan, Yuan | Zhang, Li-Li | Lu, Jian-Wei | Feng, Ji-Feng | Hu, Sai-Nan

Article Type: Research Article

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

Keywords: Gastrulation brain homeobox 2 gene silencing, Wnt/β-catenin signaling pathway, breast cancer cells, proliferation, invasion, angiogenesis

DOI: 10.3233/CBM-181466

Citation: Cancer Biomarkers, vol. 23, no. 3, pp. 405-418, 2018