Cancer Biomarkers - Volume 16, issue 2

Authors: He, Shun | Liu, Mei | Zhang, Weina | Xu, Ningzhi | Zhu, Hongxia

Article Type: Research Article

Abstract: BACKGROUND: p21-activated kinase 7 is a member of the group II p21-activated kinase (PAK) family which is known to play important role in tumorigenesis and metastasis. However, the expression of p21-activated kinase 7 in esophageal squamous cell cancers and the correlation with clinical parameters has never been investigated. OBJECTIVE: To explore the role of p21-activated kinase 7 in esophageal squamous cell cancers. METHODS: Esophageal squamous cell carcinoma samples were collected and the expression of p21-activated kinase 7 was detected by immunohistochemistry. In vitro cell invasion assay was employed in EC9706 cells and EC9706PAK7 …cells. Metastasis related genes were evaluated by Real-time PCR and Western Blot. RESULTS: In 85 samples, 44 (51.8%) samples showed strong expression and expression of PAK7 was significantly correlated with lymph node stage (p= 0.013) and TNM stage (p= 0.041). In vitro invasion assay showed that the invasion ability of EC9706 PAK7 cells increased 2.5 folds compared with EC9706 cells. PAK7 could enhance the protein levels of Vimentin and MMP10, but reduce E-cadherin, TIMP1 and TIMP2. CONCLUSION: PAK7 is overexpressed in human esophageal squamous cell cancer samples and correlated with lymph node metastasis. Show more

Keywords: Esophageal squamous cell cancer, p21-activated kinase 7, lymph node metastasis

DOI: 10.3233/CBM-150557

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 203-209, 2016

Authors: Loghin, Andrada | Bănescu, Claudia | Nechifor-Boila, Adela | Chibelean, Calin | Orsolya, Martha | Nechifor-Boila, Alin | Tripon, Florin | Voidazan, Septimiu | Borda, Angela

Article Type: Research Article

Abstract: INTRODUCTION: In the last decade, an increasing number of polymorphisms in DNA repair genes have been identified and their involvement in carcinogenesis was studied. Despite the fact that XRCC3 and XPD DNA repair genes association with several types of cancer was widely studied, their role in the development of clear cell renal cell carcinoma (CCRCC) has not been established in the European population. OBJECTIVE: The objective of this study was to investigate the association of XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms with the risk of CCRCC and the association between these …genotypes and CCRCC histopathological prognostic factors (pathologic stage, Fuhrman grade, tumor diameter). METHODS: This study included 73 patients with CCRCC and 100 healthy individuals without cancer. We used the PCR-RFLP method to determine XRCC3 and XPD genotypes. RESULTS: The XPD 751 variant genotype (Lys/Gln) was more frequent in CCRCC patients than in healthy individuals (OR = 2.92, 95%CI: 1.47-5.79, p= 0.001). Regarding the XRCC3 Thr241Met/XPD Lys751Gln combined genotypes a significant difference was found between patients and controls for Thr/Thr+Lys/Gln (OR = 5.44, 95%CI: 2.09-14.15, p= 0.0003) and for Thr/Met+Gln/Gln (OR = 11.2, 95%CI: 1.95-100.4, p= 0.01). No association was found between any of the studied genotypes and histopathological prognostic factors of CCRCC. CONCLUSIONS: Our findings indicate that XPD Lys751Gln polymorphism may be a risk factor for CCRCC. Regarding the XRCC3 Thr241Met polymorphism, an association with CCRCC was found only in XRCC3 Thr241Met/XPD Lys751Gln combined genotypes. Show more

Keywords: Gene polymorphisms, DNA repair genes, XRCC3, XPD, clear cell renal cell carcinoma

DOI: 10.3233/CBM-150558

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 211-217, 2016

Authors: DeCotiis, Christopher | Hu, Yingjie | Greenberg, Alissa K. | Huie, Maryann | Tsay, Jun-Chieh J. | Pass, Harvey | Goldberg, Judith D. | Rom, William N.

Article Type: Research Article

Abstract: BACKGROUND: Inflammatory cytokines are at the intersection of tumor cell biology and host immune response. Peripheral cytokine expression levels may reflect the microscopic tumor milieu, and specific cytokines play an integral role in tumor initiation, growth, and metastasis. High-throughput cytokine analysis may identify panels for early-stage non-small cell lung cancer (NSCLC) diagnosis and identify individuals at high-risk for lung cancer with indeterminate lung nodules 8-20 mm in size. METHODS: Thirteen serum cytokines from the NYU Lung Cancer Biomarker Center cohort with early-stage NSCLC were analyzed using bead-based immunoassay technology. RESULTS: In the NYU …cohort, a one unit increase in interferon-γ increased risk of lung cancer by 3% (OR = 1.03, 95% CI, 1.02-1.05) and a one unit increase in TNF-α decreased the risk of lung cancer by 53% (OR = 0.47, 95% Cl, 0.31-0.71) when both cytokines were included in a logistic regression model with adjustments for age and pack-years of smoking. The resulting AUC for the Receiver Operating Characteristic (ROC) curve was 0.88; the sensitivity and specificity at the optimal cutpoint were 78.9% and 90.3%, respectively. CONCLUSIONS: Cytokines have limited value in the early diagnosis of early-stage NSCLC. Our review of the literature suggests that although inflammation is important for the development of NSCLC, that cytokines are increased in more advanced lung cancer than when the diagnosis occurs at presentation. Show more

Keywords: Inflammatory cytokines, biomarkers, non-small cell lung cancer

DOI: 10.3233/CBM-150559

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 219-233, 2016

Authors: Fan, Nai-Jun | Chen, Hong-Mei | Song, Wei | Zhang, Zhan-Yang | Zhang, Miao-Dan | Feng, Li-Ying | Gao, Chun-Fang

Article Type: Research Article

Abstract: BACKGROUND: Simple blood tests that could be used for early detection are crucial for the ultimate control and prevention of colorectal cancer (CRC). In this study, we performed a serum proteomic analysis of CRC and health volunteers to identify the novel biomarkers involved in CRC. METHOD: A shotgun proteomic method was applied to identify serum proteins in the serum samples of three CRC and three health volunteers using a combination of high-performance liquid chromatography and mass spectrometry. Label-free protein profiling was conducted to quantify the proteins and compare the profiles of the CRC and health volunteers. …Two differentially expressed proteins were further validated by western blot analysis. Quantity analysis was performed through enzyme linked immunosorbent assay (ELISA) in serum from 96 healthy and 118 CRC volunteers. RESULTS: Among of the 373 identified proteins, 69 were linked to CRC (33 upregulated and 36 downregulated). The Gene Ontology and DAVID databases were used to identify the location and function of the different proteins. Among the 69 proteins linked to CRC, two proteins, namely, macrophage mannose receptor 1 (MRC1) and S100A9, were verified to be upregulated in CRC by western blot analysis and could be used to identify CRC from healthy volunteers with high accuracy through ELISA analysis. CONCLUSION: MRC1 and S100A9 may contribute to the determination of the mechanisms and screening involved in CRC. Show more

Keywords: Colorectal neoplasms, proteomics, diagnosis, macrophage mannose receptor 1, S100A9

DOI: 10.3233/CBM-150560

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 235-243, 2016

Authors: Pakdel, Abbas | Malekzadeh, Mahyar | Naghibalhossaini, Fakhraddin

Article Type: Research Article

Abstract: OBJECTIVE: Liver is the primary site for the metastasis from colorectal cancer (CRC). It has been proposed that carcinoembryonic antigen (CEA) might have an instrumental role in the development of hepatic metastasis from human CRC. The aim of the present study was therefore to investigate the association between preoperative serum CEA concentrations and the incidence of synchronous CRC-liver metastasis. METHODS: A total of 199 patients with CRC who underwent radical surgery at the Shiraz University hospitals were enrolled in this study. The preoperative serum CEA levels of patients without distant metastasis were compared with those with …hepatic metastasis and those with other organs metastasis at the time of initial diagnosis. RESULTS: Preoperative serum CEA concentrations were found to be significantly higher in patients with distant metastases compared to patients with local CRC (P < 0.001). Moreover, the mean serum CEA level in patients with liver metastasis was higher than non-metastasis group (42.89 ng/ml vs 9.62 ng/ml) (p < 0.001). We did not find significant differences in serum CEA concentrations between non-metastasis and the other organ metastasis groups (p> 0.05). CONCLUSIONS: We conclude that patients with high preoperative serum CEA levels should have more intensive follow-up for detection of synchronous liver metastasis. Show more

Keywords: Colorectal cancer, serum CEA, liver metastasis

DOI: 10.3233/CBM-150561

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 245-252, 2016

Authors: Chen, Xiaobo | Su, Zhaoliang | Wang, Shengjun | Xu, Huaxi

Article Type: Research Article

Abstract: BACKGROUND: ADP-ribosylation factor (ARF)-like 4c (Arl4c) has been reported to promote tumorigenesis in colorectal and lung cancers and may represent a novel therapeutic target. The aim of this study was to investigate the expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) in colorectal cancer (CRC) in Chinese populations and an AOM/DSS-induced mouse colorectal carcinogenesis model, and its prognostic value in patients with CRC. MATERIALS AND METHODS: Expression of Arl4c in CRC patients and AOM/DSS-induced colorectal tumors was detected using immunohistochemistry and real- Real time PCR. In addition, the correlations between Arl4c expression and clinicopathological characteristics and overall …survival were evaluated using Kaplan-Meier analysis. RESULTS: The Arl4c was statistically significantly overexpressed in CRC tissues relative to adjacent normal tissue (p= 0.001). CRC patients with high Arl4c expression tended to show poorer survival than patients with lower Arl4c expression (p= 0.069). However, the level of Arl4c expression was not visibly correlated with age, gender or tumor stage. In addition, increased expression of Arl4c was also found in AOM/DSS-induced colorectal tumors (p= 0.001), which indicated that Arl4c might play an important role in colon tumorigenesis. CONCLUSIONS: Results indicated that overexpression of Arl4c might contribute to the tumorigenesis and might play a pivotal role in the progression of CRC. Show more

Keywords: Arl4c, colorectal cancer, prognosis

DOI: 10.3233/CBM-150562

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 253-257, 2016

Authors: Zhu, Yunxiang | Xu, Andong | Li, Jinming | Fu, Jihong | Wang, Guanghui | Yang, Yili | Cui, Long | Sun, Jiwei

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related death around the world. MicroRNAs (miRNAs) are small non-coding RNAs that often are abnormally expressed in tumors. Detection and quantitation of miRNAs may provide information for the screening and early diagnosis of CRC. OBJECTIVES: The objective of our study was to determine whether fecal microRNAs (miR-29a, miR-145, miR-223, miR-224) could be used as biomarkers for the screening and early diagnosis of colorectal cancer. METHODS: We carried out a retrospective analysis of the miRNAs in fecal samples from 80 CRC patients …and 51 normal controls. The levels of 4 miRNAs (miR-29a, miR-145, miR-223, and miR-224) were quantitated using the SYBR Green miScript PCR system and 2 - Δ Δ Ct method. RESULTS: Our data indicated that the expression levels of miR-29a (p< 0.001), miR-223 (p< 0.001) and miR-224 (p< 0.001) are significantly lower in feces from CRC patients than these from normal volunteers, whereas their miR-145 levels are not significantly different (p= 0.59). Interestingly, the level of miR-29a (p< 0.001) in feces from individuals with rectum cancer is also significantly higher than that from patients with colon cancer. CONCLUSION: There are reduced expression of miR-29a, miR-223, and miR-224 in the feces from the CRC patients, which could be an informative biomarker for screening and early diagnosis of CRC. Show more

Keywords: Colorectal cancer, microRNA, noninvasive biomarker, diagnosis, screening

DOI: 10.3233/CBM-150563

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 259-264, 2016

Authors: Sun, Li | Dong, Shuling | Dong, Cuicui | Sun, Kaiyan | Meng, Weiwei | Lv, Pin | Yin, Huiqing | Ming, Liang | He, Fucheng

Article Type: Research Article

Abstract: BACKGROUND: Increasing evidence demonstrated that circulating miRNAs could serve as meaningfully non-invasive and reliable biomarkers for the detection of various cancers. OBJECTIVE: To investigate the expression level of plasma miRNA-718 in esophageal squamous cell carcinoma (ESCC) patients and its diagnostic value. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) method was performed to examine the expression levels of plasma miRNA-718 in 120 consecutive ESCC patients and 51 healthy controls. The difference of plasma miRNA-718 expression level between the paired pre- and postoperative patients was compared. The correlation between plasma miRNA-718 expression levels and …clinicopathological characteristics was further analyzed and the receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic power of plasma miRNA-718 for ESCC. RESULTS: Plasma miRNA-718 expression level of ESCC patients was significantly lower than that of healthy controls. Compared with preoperative patients, the plasma miRNA-718 expression level of postoperative patients was significantly upregulated. Plasma miRNA-718 expression level was inversely correlated with the lymph node metastasis and TNM stage. The ROC curve analysis showed that plasma miRNA-718 yielded AUCs of 0.715, 0.689 and 0.620 for the detection of ESCC patients, early patients with Tis-T1 or early patients with TNM 0-I, respectively. CONCLUSION: Plasma miRNA-718 is downregulated in ESCC patients and might serve as a potential diagnostic marker for ESCC. Show more

Keywords: Esophageal squamous cell carcinoma, microRNA-718, plasma, diagnosis

DOI: 10.3233/CBM-150564

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 265-273, 2016

Authors: Trapasso, S. | Garozzo, A. | Belfiore, A. | Allegra, E.

Article Type: Research Article

Abstract: BACKGROUND: The soluble fraction of the CD44 protein (solCD44) may constitute a valuable biological marker of Cancer Stem Cells (CSCs), useful for screening/early detection of laryngeal cancer, and for the prognosis. In previous papers, in fact, we have studied the expression of salivary solCD44 in patients with laryngeal tumors, supporting its use for early diagnosis of laryngeal carcinoma with high sensitivity and specificity, also with prognostic role, useful for clinical outcome. OBJECTIVE: The purpose of present study was to verify the levels of solCD44 isoform v6, sCD44var (v6), in saliva samples of patients with laryngeal carcinoma …in our tumoral biobank, to evaluate possible correlations with clinical-anamnestic and prognostic data. METHODS: Study design was retrospective. Salivary samples of 66 patients with laryngeal cancer recruited from January 2012 to December 2013 were selected from our tumoral biobank. For each salivary sample was performed the determination of solCD44 and its isoform v6, sCD44var (v6), by ELISA. Qualitative and quantitative results of the test were correlated with clinical and medical history data. For statistical analysis we used the software MedCalc (versione 12.2.1.0). RESULTS: Concentrations of salivary sCD44var v6 were significantly higher according to the size of the primary tumor (T) (p= 0.001), the tumor site glottic or supraglottic-transglottic (p= 0.005) and according to the metastatic lymph node involvement (p= 0005). Furthermore, tumors in advanced disease (stage III-IV) showed values of salivary sCD44var v6 higher than the tumors in early stage, with a statistically significant difference (p= 0.005). CONCLUSIONS: The determination of the levels of salivary solCD44 v6 may represent a promising prognostic test in laryngeal carcinomas. Show more

Keywords: Soluble CD44, laryngeal cancer, saliva, sCD44var (v6)

DOI: 10.3233/CBM-150565

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 275-280, 2016

Authors: Liu, Qian | Zhang, Guang-Wei | Zhu, Chao-Yang | Wei, Jin-Xing | Tian, Xin | Li, Yang | Li, Xiao-Dong

Article Type: Research Article

Abstract: BACKGROUND: Numerous previous studies explored the influence of matrix metalloproteinase 2 (MMP-2) expressions on renal cell carcinoma (RCC), yet inconsistent results were reported. OBJECTIVE: This study aims to derive a more precise estimation of the associations between MMP-2 and RCC. METHODS: A total of 115 patients with RCC were selected; meanwhile, 45 patients with traumatic rupture of renal cysts or renal calculi were recruited and normal kidney tissues were collected as control group. The expression level of MMP-2 protein was detected by using immunohistochemistry. A meta-analysis was performed by using Comprehensive Meta-analysis 2.0 …(CMA 2.0). RESULTS: The positive expression rate of MMP-2 protein in the RCC tissues was evidently higher than that in the normal renal tissues (P < 0.001). The positive expression rate of MMP-2 protein in patients with tumor size > 5 cm, with lymph node metastasis (LNM), with well-differentiated RCC, and stage III-IV RCC was significantly higher, compared with the patients with tumor size ≤ 5 cm, without LNM, with moderate/low-differentiated RCC, and with stage I-II RCC, respectively (all P < 0.05). There was statistical significance in the 5-year survival rate between the patients with positive MMP-2 protein expression and those with negative MMP-2 protein expression (P = 0.037). These results were further confirmed by the meta-analysis. CONCLUSION: MMP-2 protein expression is significantly associated with historical grade, TNM stage, tumor size and LNM in RCC, suggesting that MMP-2 may serve as a biological marker for the prognosis in RCC. Show more

Keywords: Renal cell carcinoma, matrix metalloproteinase 2, clinicopathological features, prognosis, survival rate, immunohistochemistry

DOI: 10.3233/CBM-150566

Citation: Cancer Biomarkers, vol. 16, no. 2, pp. 281-289, 2016