Cancer Biomarkers - Volume 20, issue 2

Authors: El-Abd, Eman | El-Sheikh, Marwa | Zaky, Sameh | Fayed, Wagdy | El-Zoghby, Safinaz

Article Type: Research Article

Abstract: BACKGROUND : The key regulator of tumor metabolome is the glycolytic isoenzyme M2-PK which favors the generation of nucleic acid via glutaminolysis as hypoxic adaptive mechanism in the tumor cells. AIM : The study aimed to evaluate the prognostic role of M2-PK, CRP, and CA 15-3 in preoperative and metastatic breast carcinomas. PATIENTS AND METHODS : The study included 70 females; 15 controls, 33 preoperative primary breast carcinomas clinically metastasis free, and 22 clinically diagnosed metastatic breast carcinomas. M2-PK and CA 15-3 were detected by ELISA. CRP was quantified using the CRP LATEX kit. RESULTS …: TuM2-PK significantly increased in metastatic and preoperative groups when compared to controls (p = 0.049, p = 0.001); respectively. Both CRP and CA 15-3 were significantly increased in metastatic than the preoperative group (p = 0.002). CA 15-3 was significantly increased in both groups when compared to controls (p = 0.016; p < 0.001; respectively). TuM2-PK level significantly related to tumor size in metastatic group (p = 0.006) and with menstruation status (p = 0.039), and liver metastasis (p = 0.036) in preoperative group. TuM2-PK significantly correlated with CRP (r = 0.793, p = 0.004), and CA 15-3 (r = 0.568, p = 0.006) in the metastatic group. Metastatic group with TuM2-PK ⩽ 15 U/ml had significantly higher survival rate than those with > 15 U/ml (χ 2 = 13.841, p < 0.001) within 3.3–4.2 but not after 10–20 years follow up period. Metastasis to bone and lymph nodes significantly increased in the metastatic than the preoperative group (p = 0.002, p = 0.013; respectively). Within 3.3–4.2 years, CA15.3 has the highest prognostic performance in metastatic group while both TuM2-PK and CRP have same specificity. On the other hand, TuM2-PK has the highest prognostic performance in preoperative group. After 20 years follow up period, there was neither significant difference in the performance of the three markers in predicting mortality in metastatic and preoperative groups nor in predicting metastasis in preoperative group. CONCLUSION : Current results document for the first time, a cross-talk between TuM2-PK and each of CRP and CA 15-3 in metastatic breast cancer. Show more

Keywords: Breast carcinoma, CA 15-3, CRP, immunity, inflammation, prognostic performance, TuM2-PK, tumor markers

DOI: 10.3233/CBM-160482

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 123-133, 2017

Authors: Modarres-Gilani, Mitra | Vaezi, Maryam | Shariat, Mamak | Zamani, Narges | Nourizadeh, Roghaiyeh

Article Type: Research Article

Abstract: BACKGROUND: Lifetime risk of developing endometrial cancer is 2.17%. There is controversy regarding the predictive value of Cancer Antigen 125 (CA125) in endometrial cancer as well as the significance of its relationship with prognostic factors and appropriate cut-off value. OBJECTIVE: The aim of the present study was to investigate the prognostic role of CA125 in advanced endometrial carcinoma and determination of the appropriate cut-off value. METHODS: A sample of 91 patients was retrospectively selected from a population of 501 patients suffering from endometrial cancer during 1995 to 2015 in accordance with the inclusion …criteria. The relation between clinicopathological variables and CA125 were analyzed. In order to determine sensitivity and specificity of various cut-off levels, receiver operating characteristic (ROC) curve analysis was performed for associated factors confirmed by logistic regression analysis. RESULTS: In 35% of patients, CA125 values were 35 u/ml, and in 52%, the values were equal to or greater than 20 u/ml. High preoperative CA125 was significantly related with advanced stage, ovarian involvement, omental metastasis, and myometrial invasion equal to or greater than 50%. According to the ROC curve, the suitable cut-off value for CA125 in advanced stage (sensitivity = 73%, specificity = 55%, positive predictive value = 18%, negative predictive value = 78%) and myometrial invasion equal to or greater than 50% (sensitivity = 64%, specificity = 61%, positive predictive value = 47%, negative predictive value = 74%) was 20 u/ml. Further, the suitable cut-off value for CA125 in involvement of the ovaries (sensitivity = 77%, specificity = 72%, positive predictive value = 31%, negative predictive value = 95%) and omental involvement (sensitivity = 70%, specificity = 70%, positive predictive value = 22%, negative predictive value = 95%) was 35 u/ml. CONCLUSIONS: In endometrial carcinoma, due to the relationship of CA125 with numerous prognostic factors, it is recommended that CA125 measurement be included in preoperative evaluation. In case of high CA125 levels, complete surgical staging including lymphadenectomy and omentectomy should be considered. Show more

Keywords: CA125, endometrial cancer, cut-off value

DOI: 10.3233/CBM-160529

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 135-141, 2017

Authors: Lin, Hai | Jiao, Xuelong | Yu, Benxia | Du, Jiangdong | Xu, HaiYan | Dong, Aiping | Wan, Chunsheng

Article Type: Research Article

Abstract: OBJECTIVE : The 14-3-3 family of conserved regulatory proteins comprises the isoforms beta (β ), gamma (γ ), zeta (ζ ), sigma (ε ), tau (η ), and delta (σ ), which are overexpressed and associated with a high risk of metastasis and poor survival in hepatocellular carcinoma (HCC). In the present study, we investigated whether serum 14-3-3 isoforms are related to HCC progression and patient survival. METHODS : Serum samples from 63 HCC patients who underwent surgical reSection 104 HCC patients who received non-surgical anti-HCC treatments, …50 patients with liver cirrhosis alone, 45 patients with chronic hepatitis alone, and 50 healthy subjects were collected between January 2006 and December 2010. Serum levels of 14-3-3 (β , ε , γ , σ , and ζ ) isoforms were measured by ELISA. The correlation between 14-3-3 (β and σ ) isoforms and clinicopathological factors was examined by logistic regression analysis. The feasibility of serum 14-3-3 β for discriminating HCC patients was assessed by ROC curve analysis. Patient survival analyses were performed by Kaplan-Meier analyses and Cox regression models. RESULTS: Serum levels of 14-3-3 (β and σ ) were significantly higher in HCC patients than in those with liver cirrhosis, chronic hepatitis, and healthy subjects (p < 0.05). There was no difference in the serum levels of 14-3-3 ε , γ , and ζ between HCC and the other groups (p > 0.05). High levels of serum 14-3-3 β were associated with vascular invasion (p = 0.016), TNM stage (p = 0.012), BCLC stage (p = 0.01), and early recurrence (p = 0.013). Patients with high levels of serum 14-3-3 β had a poor prognosis. There was no significant association between 14-3-3 σ levels and clinicopathological parameters. A significant independent association between serum 14-3-3 β and HCC was observed by univariate and multivariate analysis (p < 0.05). Serum 14-3-3 β could effectively discriminate HCC patients at a cut-off point of 18.7 ng/mL, with 91.4% sensitivity and 75.3% specificity. CONCLUSIONS : Serum 14-3-3 β is a potential biomarker for the diagnosis of early-stage HCC, and high levels of serum 14-3-3 β were associated with metastasis and poor prognosis in HCC. Show more

Keywords: Hepatocellular carcinoma, prognosis, 14-3-3 family proteins

DOI: 10.3233/CBM-160533

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 143-150, 2017

Authors: Todorović-Raković, Nataša | Radulovic, Marko | Vujasinović, Tijana | Rabi, Zaki Abu | Milovanović, Jelena | Nikolić-Vukosavljević, Dragica

Article Type: Research Article

Abstract: BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenic and mitogenic factor that has been functionally predisposed to promote tumorigenesis, while literature data also associate bFGF with a favorable outcome of breast cancer. OBJECTIVE: In order to help resolve such controversy, this study set out to investigate the role of bFGF in breast cancer for the first time by use of the node-negative patient group with smaller tumors and without any systemic adjuvant therapy. This has allowed an increased homogeneity of the group and a far more reliable interpretation of results. METHODS: …The study included 133 node-negative breast cancer patients with 33 distant metastasis events. bFGF levels were determined by ELISA in primary tumor tissue homogenates. RESULTS: bFGF in primary tumor tissue associated with favorable breast cancer outcome and its levels significantly and positively correlated with ER levels. CONCLUSIONS: The obtained results are relevant for the future prognostic research aimed at surpassing the currently achievable prognostic accuracies which are by far inadequate to allow reliable therapeutic decision making in breast cancer. Show more

Keywords: Breast cancer, bFGF, estrogen receptor, prognosis, metastasis

DOI: 10.3233/CBM-170022

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 151-158, 2017

Authors: Li, Wuping | Zhong, Yun | Shuang, Yuerong | Huang, Hui | Huang, Yan | Yu, Li | Huang, Xianbao

Article Type: Research Article

Abstract: BACKGROUND: Lymphoma associated hemophagocytic syndrome (LAHS) is one of the major adult secondary hemophagocytic lymphohistiocytosis (HLH). Early diagnosis and treatment contribute to improved outcome. No enlarge lymph nodes can often delay the diagnosis of underlying lymphoma. OBJECTIVE: To find out criteria distinguishing LAHS from HLH induced by benign diseases. METHODS: clinical characteristic and laboratory feature of 31 patients with HLH (10 benign disease-associated HLH and 21 LAHS) were analyzed retrospectively. RESULTS: No significantly differences were observed in the levels of LDH, IL-6, IL-10, TNF-α ; however, the level of …CRP (C reactive protein) and the mean level of sIL-R (soluble interleukin-2 receptor) were higher in patients with LAHS than those with benign disease associated disease associated HLH while ferritin levels were higher in benign disease associated HLH than in LAHS. Consequently, the serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease associated HLH (0.33 ± 0.23 vs 5.82 ± 3.26, P = 0.0001). In addition, we found out that the mean level of miR-133 (microRNA-133) was significant higher in LAHS than in benign disease associated HLH (18.83 ± 10.44 vs 5.82 ± 3.26, P ⩽ 0.0001). Conclusion: Serum miR-133 is a new very useful marker for diagnosing of LAHS, but it need further confirmation by further clinical studies. Show more

Keywords: Lymphoma-associated hemophagocytic syndrome, lymphoma, soluble interleukin-2 receptor, ferritin, miR-133

DOI: 10.3233/CBM-170054

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 159-164, 2017

Authors: Zhao, Tianhe | Wu, Lichun | Li, Xinyang | Dai, Huangmei | Zhang, Zunzhen

Article Type: Research Article

Abstract: BACKGROUND: Recent study has revealed that large intergenic non-coding RNA-ROR (linc-ROR) is aberrantly expressed in a number of cancers including breast cancer. However, whether circulating linc-ROR in plasma could be used for breast cancer diagnosis and dynamic monitoring is not clear. OBJECTIVE: The objective of this study is to determine if plasma linc-ROR could be applied as a biomarker for the diagnosis and dynamic monitoring of breast cancer. METHODS: We tested the expression levels of linc-ROR in 24 pairs of tissue samples and 96 plasma samples from breast cancer patients by quantitative real …time-polymerase chain reaction (qRT-PCR), and analyzed the correlation between plasma linc-ROR levels and clinico-pathological characteristics. Receiver operating characteristic (ROC) curve was used to assess the diagnostic power of plasma linc-ROR, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)153 for breast cancer. Furthermore, we explored the monitoring values of plasma linc-ROR for breast cancer by analyzing the preoperative and postoperative plasma linc-ROR levels of the same patients. RESULTS: The expression levels of linc-ROR were significantly higher in breast cancer tissues and plasma than the levels in the control (P < 0.05). The linc-ROR expression levels in plasma were correlated with lymph node metastasis (P < 0.05), estrogen receptor (ER) (P < 0.05) and progesterone receptor (PR) (P < 0.05). The area under the ROC curve of plasma linc-ROR was 0.758 (sensitivity 80.0%; specificity 73.3%), which was higher than CEA and CA153 values from the same patients obtained. Combination of the linc-ROR with the conventional biomarkers might produce better diagnostic ability. Additionally, the linc-ROR expression levels of plasma in postoperative patients were lower than those in preoperative patients (P < 0.05). CONCLUSION: Overexpressed linc-ROR may be a potential biomarker for the diagnosis and dynamic monitoring of breast cancer. Show more

Keywords: Long non-coding RNAs, linc-ROR, breast cancer, biomarker

DOI: 10.3233/CBM-170064

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 165-173, 2017

Authors: Li, Yu | Jia, Changxin | Zhang, Dianlong | Ni, Guangzhen | Miao, Xia | Tu, Ruirong

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Studies in developing animals have demonstrated that when anesthetic agents, such as propofol, are early administered in life, it can lead to neuronal cell death and learning disabilities. However, the mechanisms causing these effects remains unknown. A recent report found that propofol could significantly upregulat miR-206 expression in the human ASCs. miR-206 could also induce apoptosis in human malignant cancers. Therefore, in this study, we hypothesized that propofol induces neurotoxicity in human embryonic stem cells (hESCs). METHODS: hESCs were exposed to propofol (50 μ M) for 6 hr and cell death was assessed using …TUNEL staining, and cleaved caspase-3 expression. miR-206 was knocked down using antagomir. PUMA was knocked down using a small interfering RNA. microRNA-206 (miR-206) expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). PUMA protein expression was detected using western blot assay. RESULTS: hESCs exposed to propofol showed a significant increase in TUNEL positive cells and cleaved caspase-3 expression, followed by the upregulation of miR-206 and PUMA expression. Targeting PUMA inhibits propofol-induced cell apoptosis; miR-206 knockdown decreased propofol-induced cell apoptosis, cleaved caspase-3 and PUMA expression. CONCLUSIONS: Propofol induce s cell death in hESC-derived neurons via activation of miR-206/PUMA signal pathway. Show more

Keywords: Propofol, neurotoxicity, miR-206, PUMA

DOI: 10.3233/CBM-170167

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 175-181, 2017

Authors: Zuo, Mingrong | Li, Mao | Chen, Ni | Yu, Tianping | Kong, Bing | Liang, Ruofei | Wang, Xiang | Mao, Qing | Liu, Yanhui

Article Type: Research Article

Abstract: BACKGROUND: While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. OBJECTIVE: IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III–IV). METHODS: We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them. We analyzed expressions of molecules as follow: IDH1/2, P53, Ki-67, …ATRX, PTEN, MMP9 and MGMT by Immunohistochemistry (IHC). Direct gene sequencing was performed to test the IDH1(R 132H) mutation. RESULTS: We found a significant difference of IDH1 mutation between those high-grade gliomas, with 92% (46/50) of the thalamic tumors and 71% (66/93) of the superficial gliomas showing IDH1 wild-type (p = 0.004). It also showed that IDH1 mutation in superficial glioblastomas 18.6% (13/70) occurred more than thalamic glioblastomas 2.6% (1/39) (p = 0.017). As to high-grade superficial gliomas, there were 26 patients with IDH1 mutation, which contained 7, 13, and 6 high, moderate and low Ki-67 expression gliomas, respectively. The IDH1 wild-type group (62 patients), was composed of 29, 30, and 3 high, moderate and low Ki-67 expression gliomas, respectively. There was a significant distinction between the IDH1 mutation and Ki-67 expressions (p = 0.024). We also noted that the occurrence of low Ki-67 expressions 23.1% (6/26) in IDH1 mutation group was outnumbered than IDH1 wild-type group 4.8% (3/62) (p = 0.018). In addition, we found PTEN negative correlated with MMP9 negative in thalamic high-grade gliomas, whereas no such difference was found in superficial gliomas (p = 0.016). CONCLUSION: The rare occurrence of IDH1 mutant high-grade thalamic gliomas strongly suggested that the high-grade thalamic glioma is another distinct tumor entity as compared to the high-grade superficial gliomas. Show more

Keywords: High-grade Glioma, thalamus, superficial cerebrum, IDH1 mutation

DOI: 10.3233/CBM-170175

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 183-189, 2017

Authors: Wu, Hong-Kun | Liu, Chang | Fan, Xiao-Xia | Wang, Hao | Zhou, Lin

Article Type: Research Article

Abstract: OBJECTIVE: The study aimed to investigate the role of spalt-like transcription factor 4 (SALL4) in the diagnosis and prognosis of colorectal cancer (CRC). METHODS: Between May 2008 and January 2010, 135 patients with CRC were recruited and subsequently assigned into the case group of the study. Additionally, 140 healthy individuals under identical conditions were selected as the control group. Venous blood was collected from all subjects. High expression of SALL4 was detected by immunohistochemistry, and SALL4 serum levels were detected using ELISA. A 5-year follow-up was conducted. A Kaplan-Meier curve was applied for analysis of survival …rates, and a log-rank was used for univariate analysis. RESULTS: The case group exhibited largely positive expression levels of SALL4. Levels of SALL4 serum were much higher than those in the control group. The AUC value of CRC detected by serum SALL4 was 0.916 (95% CI was 0.881–0.951), which regarded 0.1255 μ cg/l to be the point of critical value. This result was in direct relation to data from the receiver operating characteristic curve (ROC). The sensitivity and specificity of serum SALL4 levels in the diagnosis of CRC were 85.9% and 85.7%, respectively. The AUC value of CRC detected by tissue SALL4 was 0.727 (95% CI was 0.666–0.789), 0.5 was regarded as the critical value. The sensitivity and specificity of SALL4 expression in CRC tissues regarding the diagnosis of CRC was determined to be 58.6% and 86.9% respectively. The levels of SALL4 expression in serum and tissues highlighted a correlation to lymph node metastasis (LNM), differentiation degree, Dukes staging and tumor node metastasis staging. Lower serum SALL4 levels were associated with higher survival rates in CRC patients. In accordance with a COX regression, LNM, differentiation degree and SALL4 levels were determined as being prognostic factors in patients with CRC (both P < 0.05). CONCLUSION: Our experimental data indicated that over expression of SALL4 was found in CRC and low expression of SALL4 was connected with high survival rate after surgery. Thus our study suggested that SALL4 could serve as a potential diagnostic and prognostic marker of CRC. Show more

Keywords: Spalt-like transcription factor 4, colorectal cancer, diagnosis, prognosis, lymph node metastasis, tumor

DOI: 10.3233/CBM-170204

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 191-198, 2017

Authors: Chen, Wen-Jing | Ye, Jing-Ying | Li, Xin | Xu, Jia | Yi, Hai-Jin

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to discuss clinical characteristics, image manifestation and treatment methods of temporal bone lesions with facial paralysis as the main manifestation for deepening the understanding of such type of lesions and reducing erroneous and missed diagnosis. METHODS: The clinical data of 16 patients with temporal bone lesions and facial paralysis as main manifestation, who were diagnosed and treated from 2009 to 2016, were retrospectively analyzed. Among these patients, six patients had congenital petrous bone cholesteatoma (PBC), nine patients had facial nerve schwannoma, and one patient had facial nerve hemangioma. All the patients had …an experience of long-term erroneous diagnosis. RESULTS: The lesions were completely excised by surgery. PBC and primary facial nerve tumors were pathologically confirmed. Facial-hypoglossal nerve anastomosis was performed on two patients. HB grade VI was recovered to HB grade V in one patient. The anastomosis failed due to severe facial nerve fibrosis in one patient. Hence, HB remained at grade VI. Postoperative recovery was good for all patients. No lesion recurrence was observed after 1–6 years of follow-up. CONCLUSION: For the patients with progressive or complete facial paralysis, imaging examination should be perfected in a timely manner. Furthermore, PBC, primary facial nerve tumors and other temporal bone space-occupying lesions should be eliminated. Lesions should be timely detected and proper intervention should be conducted, in order to reduce operation difficulty and complications, and increase the opportunity of facial nerve function reconstruction. Show more

Keywords: Petrous bone cholesteatoma, facial nerve tumor, facial nerve function, facial paralysis

DOI: 10.3233/CBM-170361

Citation: Cancer Biomarkers, vol. 20, no. 2, pp. 199-205, 2017