Cancer Biomarkers - Volume 19, issue 3

Authors: Choi, Boram | Lee, Hyuk-Joon | Min, Jimin | Choe, Hwi-Nyeong | Choi, Yun-Suk | Son, Young-Gil | Ahn, Hye-Seong | Suh, Yun-Suhk | Goldenring, James R. | Yang, Han-Kwang

Article Type: Research Article

Abstract: BACKGROUND: Few reliable blood markers are available for detecting gastric cancer, mainly owing to the heterogeneity of the cancer. OBJECTIVE: To establish gastric cancer diagnostic markers, we evaluated the levels of plasma cadherin 17 (CDH17) and trefoil factor 3 (TFF3), which are secretory proteins and known markers for intestinal metaplasia (IM), in patients with gastric cancer. METHOD: The protein expression level was analyzed in blood plasma samples from 111 gastric cancer patients and 44 healthy individuals, using a sandwich ELISA kit, followed by statistical analyses. RESULT: Overall, the plasma levels …of CDH17 and TFF3 were not significantly different between groups (p = 0.160 and p = 0.113, respectively). However, CDH17 expression was significantly elevated in patients with stage II and III gastric cancers compared to that in healthy controls (p = 0.023 and p = 0.037, respectively). In contrast, TFF3 levels were significantly elevated in patients with stage I (p = 0.001) and T1 gastric cancer (p = 0.013). The sensitivity and specificity of CDH17 were 66.7 and 61.4%, respectively (cutoff point: 0.189 ng/mL); for TFF3, these values were 62.2 and 56.8%, respectively (cutoff point: 5.215 ng/mL). CONCLUSIONS: These findings indicate that secretory protein markers for metaplastic lineages can be used as blood markers for gastric cancer. Show more

Keywords: CDH17, TFF3, ELISA, gastric cancer marker

DOI: 10.3233/CBM-160147

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 231-239, 2017

Authors: Liu, Jiaxiu | Xu, Bin | Xu, Guoying | Zhang, Xiaolei | Yang, Xueyi | Wang, Jiandong

Article Type: Research Article

Abstract: BACKGROUND: Eph receptors comprise the largest group of the receptor tyrosine kinase (RTK) family, and Eph receptors interacting with their ligand ephrins play an important role in development and tumorigenesis. EphB6, a special Eph receptor that lacks tyrosine kinase activity, was reported to be expressed in some human cancers. The clinical significance of EphB6 in gastric carcinoma has not been well investigated. METHODS: In this study, we detected expression of EphB6 protein in four gastric cancer cell lines and a set of gastric carcinoma tissue specimens by using immunohistochemistry. The relationship between EphB6 protein expression and …clinicopathological parameters was statistically analyzed. RESULTS: EphB6 protein was differentially detected in four gastric cancer cell lines. EphB6 protein was low expressed in 52.6%, moderately expressed in 32.59%, and strongly expressed in 14.5% of gastric carcinomas. EphB6 expression was positively associated with tumor differentiation (P < 0.001, r s = 0.476), and negatively associated with lymph node metastasis (P < 0.001, r s = - 0.444) and tumor stage (P = 0.001, r s = - 0.269). Low EphB6 expression was detected more often in female patients (P = 0.031). No significant relationship between EphB6 expression and patient age, tumor location, or depth of tumor invasion was identified. CONCLUSION: Our data indicate that EphB6 protein was decreased in gastric carcinoma compared with normal mucosa. Analytic results based on pathological parameters suggests that EphB6 protein may inhibit metastasis of gastric carcinoma and could be a potential therapeutic target for gastric carcinoma. Show more

Keywords: EphB6, receptor tyrosine kinase, gastric carcinoma

DOI: 10.3233/CBM-160256

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 241-248, 2017

Authors: Hou, Shi-Zhen | Cheng, Zi-Ming | Wu, Yu-Bing | Sun, Yi | Liu, Bing | Yuan, Mao-Xi | Wang, Xiang-Dong

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study is to compare surgery with adjuvant chemoradiotherapy versus non-surgical treatments for patients with early-stage small cell lung cancer (SCLC) based on the short-term and long-term efficacy. METHODS: SCLC patients who underwent a pulmonary lobectomy with post-surgical radiotherapy or chemotherapy were assigned to the surgical group. SCLC patients who received radiotherapy or chemotherapy alone were classified into the non-surgical group. The clinical efficacy was evaluated as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). The total effectiveness rate was calculated as CR + …PR. The 1-, 3-, and 5-year survival rates of the two groups were compared. RESULTS: Compared with the non-surgical group, the CR rate and the total effectiveness rate were higher in the surgical group, and the total effectiveness rate for male patients and patients without a smoking history were also higher in the surgical group. Distant metastasis and local recurrence concurrent with distant metastasis in the surgical group were both lower in the surgical group than in the non-surgical group. Compared with the non-surgical group, the local recurrence in male patients was lower in the surgical group, and patients in the surgical group had lower distant metastasis at TNM stage IIb. The 1-, 3-, and 5-year survival rates were higher in the surgical group than in the non-surgical group. CONCLUSIONS: These findings indicate that for patients with early-stage SCLC, better scores in effectiveness rate, disease progression, and 1-, 3-, and 5-year survival rates were observed in patients who underwent surgery followed by adjuvant chemoradiotherapy when compared with patients without surgical treatment. Show more

Keywords: Small cell lung cancer, pulmonary lobectomy, chemotherapy, radiotherapy, effective rate, disease progressive, survival rate

DOI: 10.3233/CBM-160332

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 249-256, 2017

Authors: Zhang, Jian | Lin, Hai | Wang, Xiao-Ying | Zhang, Dong-Qin | Chen, Jian-Xia | Zhuang, Yan | Zheng, Xiao-Li

Article Type: Research Article

Abstract: OBJECTIVE: The study aims to evaluate the predictive value of microRNA-143 (miR-143) for the prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Between October 2010 and October 2012, 131 HCC patients were selected as a case group; meanwhile, 122 healthy controls were enrolled as a control group. The miR-143 expression in serum was detected by quantitative real-time polymerase chain reaction (qRT-PCR). These HCC patients were divided into the high miR-143 expression group and the low miR-143 expression group based on the threshold of receiver operating characteristic (ROC) curve. Kaplan-Meier method was applied to analyze the prognosis …of HCC patients. RESULTS: MiR-143 exhibited decreased expression in the case group significantly compared to the control group. The areas under the ROC curve (AUC), sensitivity value and specificity value of the miR-143 expression for the diagnosis of HCC were 0.831, 80.30% and 82.40%, respectively. The miR-143 expression was negatively correlated with vascular invasion, TNM staging, tumor recurrence, metastasis and survival of HCC patients. CONCLUSIONS: Our study provides evidence that miR-143 may be negatively correlated with the prognosis of HCC and provides a promising strategy for HCC treatment and prognosis improvement. Show more

Keywords: MicroRNA-143, hepatocellular carcinoma, prognosis, predictive value

DOI: 10.3233/CBM-160357

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 257-262, 2017

Authors: Yang, Na | Qu, Yan-Jun | Cheng, Yan | Liang, Tian | Zhang, Mei-Na | Zhang, Dan | Dong, Li-Na | Wang, Xiao-Wei | Zhang, Guang-Mei

Article Type: Research Article

Abstract: OBJECTIVE: The study is to explore the role of tunicamycin-induced endoplasmic reticulum stress (ERS) in human ovarian cancer (OC) SKOV3 cells proliferation, migration and invasion by modulating the activity of PI3K/AKT/mTOR pathway. METHODS: The collected human OC SKOV3 cells were randomly separated into three groups: The control group, the Tun group (treated with tunicamycin to induce ERS) and the CHOP-si group (transfected with CHOP-siRNA before tunicamycin treatment). CCK-8 method was applied for testing cell proliferation, while flow cytometry was conducted to detect cell apoptosis. Scratch test and Transwell test were used to determine the level of …cell migration and invasion, respectively. Western blotting was performed to determine the related proteins expressions in ERS and PI3K/AKT/mTOR pathway. RESULTS: The cell survival rate in the Tun group was enhanced than that in the CHOP-si group, both of which were declined with the passage of time. The cell apoptosis rate in the Tun group was increased compared to the CHOP-si group, both of which were significantly elevated. The horizontal migration distance and the number of invasive cells in the Tun and CHOP-si groups were inhibited; however, the horizontal migration distance and the number of invasive cells in the CHOP-si group were enhanced than that in the Tun group. In comparison with the control group, the expressions of CHOP and TRB3 were increased in the Tun group but decreased in the CHOP-si group. The PI3K, p-AKT and p-mTOR expressions were remarkably declined in the Tun group than those in the control group (P < 0.05). CONCLUSION: The study provides strong evidence that tunicamycin-induced ERS induces the apoptosis of human OC SKOV3 cells through inhibiting PI3K/AKT/mTOR signaling pathway. Show more

Keywords: Endoplasmic reticulum stress, ovarian cancer, SKOV3 cells, PI3K, AKT, mTOR signaling pathway

DOI: 10.3233/CBM-160424

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 263-269, 2017

Authors: Shen, Yuan | Wang, Xiaoyu | Xu, Jianping | Lu, Lin

Article Type: Research Article

Abstract: The SerpinE2 pathway is evolutionarily conserved and plays an important role in tumorigenesis. SerpinE2 (a small ubiquitin-related modifier), like ubiquitin, conjugates SerpinE2 proteins onto lysine residues of target proteins. SerpinE2 over-expression has been found in several tumors. Here, we detected the level of SerpinE2 in 72 samples of EC tissue using immunohistochemistry to assess the role of SerpinE2 in EC prognosis. Meanwhile, we knocked down SerpinE2 by siRNA in the HTB-111 and Ishikawa EC cell lines and analyzed the viability and mobility change using an MTT assay, an annexin V/PI apoptosis assay, a wound scratch test and a transwell assay. …A Kaplan-Meier analysis indicated a negative correlation between the level of SerpinE2 and the EC prognosis. Silencing SerpinE2 induced cell apoptosis and reduced the migration ability. Our data suggest SerpinE2 works as an oncogene in EC. Show more

Keywords: Endometrial cancer, SerpinE2, siRNA

DOI: 10.3233/CBM-160442

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 271-278, 2017

Authors: Hussein, Samia | Mosaad, Hala | Rashed, Hayam E. | El-Anwar, Mohammad W.

Article Type: Research Article

Abstract: BACKGROUND: Despite the improvement in the diagnosis and the management of laryngeal squamous cell carcinoma (LSCC), many patients with advanced-stage have poor prognosis in the form of recurrence, metastasis or death. So, recognition of new molecular markers would facilitate the development of targeted therapies. OBJECTIVES: To investigate miR-221 expression in LSCC and its possible correlation to apoptotic protease activating factor-1 (Apaf-1). Also, we aimed to investigate the association between miR-221 and Apaf-1 expressions and the clinicopathological features of LSCC. METHODS: We investigated the expression of miR-221 (by qRT-PCR) and Apaf-1 (by qRT-PCR and …immunohistochemistry) in primary LSCC and adjacent normal tissues. RESULTS: We found significant up-regulation of miR-221 and significant down-regulation of Apaf-1 expression in LSCC tissues compared to normal nearby laryngeal tissues. In addition, significant associations between up-regulated miR-221 and down-regulated Apaf-1 expressions and clinical stage and lymph node (LN) metastasis (P < 0.001 for each) were found. Furthermore, there was a negative correlation between miR-221 gene expression and Apaf-1 gene expression (r = - 0.73, P < 0.001). CONCLUSION: miR-221 can be considered as a diagnostic marker in LSCC and Apaf-1 may be considered as a possible target of miR-221. Show more

Keywords: Laryngeal squamous cell carcinoma, miR-221, Apaf-1

DOI: 10.3233/CBM-160444

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 279-287, 2017

Authors: Su, Ying | Zhao, An | Cheng, Guoping | Xu, Jingjing | Ji, Enming | Sun, Wenyong

Article Type: Research Article

Abstract: BACKGROUND: Renal cell carcinoma (RCC) is the highest mortality rate of the genitourinary cancers, and the treatment options are very limited. Thus, identification of molecular mechanisms underlying RCC tumorigenesis, is critical for identifying biomarkers for RCC diagnosis and prognosis. OBJECTIVE: To validate whether the IGF-I/JAK2-STAT3/miR-21 signaling pathway is associated with human RCC cell growth. METHODS: qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels, respectively. The MTT assay was performed to determine cell survival rate. The Annexin V-FITC/PI apoptosis detection kit was used to detect cell apoptosis. We …employed RCC tissues and cell lines (A498; ACHN; Caki-1; Caki-2 and 786-O) in the study. IGF-I, and its inhibitor (NT-157) were administrated to detect the effects of IGF-I on the expression of miR-21 and p-JAK2. JAK2 inhibitor (AG490), and si-STAT3 were used to detect the effects of JAK2/STAT3 signaling pathway on the expression of miR-21. RESULTS: In our study, we firstly showed that the expression levels of IGF-I and miR-21 were up-regulated in RCC tissues and cell lines. After exogenous IGF-I treatment, the expression levels of miR-21, p-IGF-IR and p-JAK2 were significantly increased, whereas NT-157 treatment showed the reversed results. Further study indicated that JAK2 inhibitor or si-STAT3 significantly reversed the IGF-I-induced miR-21 expression level. Finally, we found that IGF-I treatment significantly prompted human RCC cell survival and inhibited cell apoptosis, and NT-157 treatment showed the reversed results. CONCLUSIONS: The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human RCC cell growth. Show more

Keywords: IGF-I, JAK2-STAT3, miR-21, renal cell carcinoma

DOI: 10.3233/CBM-160449

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 289-296, 2017

Authors: Canto, Patricia | Granados, Jesús Benítez | Feria-Bernal, Guillermo | Coral-Vázquez, Ramón Mauricio | García-García, Eduardo | Tejeda, María Elena | Tapia, André | Rojano-Mejía, David | Méndez, Juan Pablo

Article Type: Research Article

Abstract: BACKGROUND: Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition. OBJECTIVE: To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. SUBJECTS AND METHODS: Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass …index (BMI) was determined and the degree of prostate cancer aggressiveness by the D’Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A , and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed. RESULTS: A higher-risk (D’Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A , and rs501299 of ADIPOQ , as well as with one haplotype of ADIPOQ was documented. CONCLUSIONS: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity. Show more

Keywords: Aggressive prostate cancer, overweight, obesity, polymorphisms, PPARGC1A, ADIPOQ

DOI: 10.3233/CBM-160467

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 297-303, 2017

Authors: Li, Lei | Wang, Wei | Zhang, Renya | Liu, Jianli | Yu, Juan | Wu, Xiaoxiao | Xu, Ying | Ma, Ming | Huang, Jian

Article Type: Research Article

Abstract: BACKGROUND: LAMP2 is one of the major protein components of lysosome. In addition to the expression on the lysosomal membrane, LAMP2 has also been found relocalizing to the cell surface of some highly metastatic tumor cells. OBJECTIVE: The aim of this study was to detect the expression levels of LAMP2 and discuss its roles in esophageal squamous cell carcinoma (ESCC). METHODS: Six hundred and ten tissue samples of ESCC were collected to construct tissue microarrays, which were stained by immunohistochemistry. RESULTS: After immunohistochemical staining, 596 patients including 460 men and 136 …women were analyzed. The LAMP2 expression levels were significantly different based on degrees of histological differentiation (χ 2 = 108.906, P < 0.001). The similar results were also observed in TNM stages (χ 2 = 23.835, P < 0.01). LAMP2 expression levels negatively correlated with degrees of histological differentiation (P < 0.01). Logistic regression analysis showed that the LAMP2 expression levels were correlated with the degrees of histological differentiation (OR= 𝑑𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑡𝑖𝑎𝑡𝑖𝑜𝑛 0.452, P < 0.001) and TNM stages (OR= 𝑇𝑁𝑀 1.482, P = 0.42). Besides, Kaplan-Meier survival curves indicated that patients with higher expression of LAMP2 exhibited poor prognosis (P < 0.05). CONCLUSIONS: Our results demonstrated that LAMP2 expression levels correlated with tumor histological differentiation and TNM stages. High expression of LAMP2 predicts poor prognosis in patients with ESCC. Show more

Keywords: LAMP2, differentiation, esophageal tumor, immunohistochemistry, survival analysis

DOI: 10.3233/CBM-160469

Citation: Cancer Biomarkers, vol. 19, no. 3, pp. 305-311, 2017