Cancer Biomarkers - Volume 21, issue 3

Authors: Xiao, Hua | Liu, Wen | Zhao, Zhenzhen | Zhang, Yan | Song, Yingying | Luo, Bing

Article Type: Research Article

Abstract: BACKGROUND: Gap junction protein beta 2 gene (GJB2) encodes one of connexins- Connexin 26 (Cx26), which mainly expressed in epithelial cells. Cx26 is usually considered a channel to exchange information between cells, which plays a critical role in tumor cell proliferation. OBJECTIVE: We investigated GJB2 rs2274084 polymorphism in three types of tumors, including nasophoryngeal carcinoma (NPC), gastric cancer (GC) and lymphoma. METHODS: Proteinase K digestion and phenolchloroform purification and QIAamp DNA FFPE tissue kit was used for DNA extraction. The genotype of GJB2 gene rs2274084 was detected through Sequenom MassARRAY SNP technique. The …Chi-square test and Fisher’s exact test were used to compare the differences between two groups. RESULTS: The genotype frequency of GJB2 gene rs2274084 was significantly different between EBV-positive NPC and normal control (P < 0.05). However, for EBV-associated gastric cancer (EBVaGC), EBV-negative gastric cancer (EBVnGC) and lymphoma, no significant differences were found in comparison with the normal control. CONCLUSIONS: The mutation rate of TT genotype was a risk factor to the occurrence of EBV-positive NPC. Show more

Keywords: SNP, GJB2, Connexin 26, EBV, NPC

DOI: 10.3233/CBM-170078

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 499-504, 2018

Authors: Hogendorf, Piotr | Durczyński, Adam | Skulimowski, Aleksander | Kumor, Anna | Poznańska, Grażyna | Strzelczyk, Janusz

Article Type: Research Article

Abstract: BACKGROUND: Pancreatic cancer (PDAC) will have been the second leading cancer-related death in the United States by 2020, according to current estimation. Its late manifestation and the lack of good early detection methods are the cause of extremely low survival rates. Therefore, there is an urgent need to develop highly sensitive and specific marker. GDF-15, a member of TGFbeta family, has recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE: Our aim was to assess the potential of GDF-15, IL-17, IL-23 serum concentration, and the panel of PDAC markers in …differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Sixty-three consecutive patients operated on due to pancreatobiliary lesions were enrolled in this study. Levels of CEA, CA125 and Ca19-9 were assessed using standard laboratory protocols. A sample of serum was collected prior to the surgery via central line. Levels of GDF-15, Il-17, Il-23 were measured using a ELISA kit. After standard pathological examination of specimens obtained on surgery, patients were divided into 2 groups: 42 patients with pancreatic adenocarcinoma and 21 patients with focal chronic pancreatitis. RESULTS: Mean GDF-15 concentration in patients with CP vs PDAC was 2247.95 (± 179.27) vs 7694.58 (± 1878.94) [pg/mL] respectively (p = 0.011). Mean concentration of Il-17, Il-23, Ca19-9, Ca125, Ca15-3, CEA in patients with CP and PDAC was 862.36 (± 30.84) vs 841.83 (± 33.94) p = 0.833; 127.85 (± 5.87) vs 127.51 (± 9.74) p = 0.175; 34.95 (± 23.34) vs 266.62 (±  49.7) p = 0.001; 13.4 (± 1.6) vs 39.27 (± 6.85) p = 0.005; 18.4 (± 1.48) vs 20.2 (± 1.38) p = 0.416; 1.96 (± 0.38) vs 5.93 (± 1.74) p = 0.004 respectively. In order to compare these markers with the routinely used ones, ROC curve was built. CA19-9 with clinically used cut-off point of ⩾ 36 IU/mL has specificity of 90.5% and sensitivity of 57.14%. At the same time GDF-15 with the optimal cut-off point of 2.7 ng/mL has specificity of 76.19% and sensitivity of 73.8%. Although in our research group CA19-9 has an excellent specificity, its usefulness is hampered by its low sensitivity. On the other hand, GDF-15 parameters are well-balanced making it a more useful biomarker of PDAC. CONCLUSIONS: In conclusion, GDF-15 is more accurate than Ca19-9 in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Interleukin 17 and 23 cannot be considered as PDAC biomarkers. GDF-15 concentration in serum should be further investigated in order to assess their usefulness in pancreatic adenocarcinoma diagnosis. Show more

Keywords: Pancreatic cancer, pancreatic adenocarcinoma, focal chronic pancreatitis, cancer biomarker, GDF-15, Il-17, Il-23, Ca19-9, Ca15-3, Ca125, CEA, panel of biomarkers

DOI: 10.3233/CBM-170203

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 505-511, 2018

Authors: Yu, Benxia | Gao, Wei | Zhou, Hui | Miao, Xia | Chang, Yuan | Wang, Liping | Xu, Miao | Ni, Guangzhen

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Propofol, an intravenous anesthetic agent, has been found to inhibit growth of breast cancer cells. However, the mechanisms underlying the antitumor are not known. A recent report has found that propofol could significantly downregulate miR-24 expression in the human malignant cancers. In breast cancer cells, overexpression of miR-24 promotes cell proliferation and inhibits cell apoptosis by downregulation of p27. The miR-24 has been reported to be overexpressed in breast cancer and breast cancer cell lines. In the present study, we hypothesized that propofol induces apoptosis of breast cancer cells by miR-24/p27 signal pathway. METHODS: …Breast cancer MDA-MB-435 cells were exposed to propofol (10 μ M) for 6 hr and cell death was assessed using TUNEL staining, Flow cytometry and cleaved caspase-3 expression. microRNA-24 (miR-24) expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-24 was overexpressed using a miR-24 mimic. P27 was knocked down using a small interfering RNA. p27 and cleaved caspase-3 expression was assessed by Western blot. RESULTS: MDA-MB-435 exposed to propofol showed a significant increase in apoptotic cells, followed by the downregulation of miR-24, upregulation of p27 expression and cleaved caspase-3 expression. Targeting p27 inhibits propofol-induced cell apoptosis; miR-24 overexpression decreased propofol-induced cell apoptosis, cleaved caspase-3 and p27 expression. CONCLUSIONS: Propofol induces cell death in MDA-MB-435 cells via inactivation of miR-24/p27 signal pathway. Show more

Keywords: Propofol, breast cancer, miR-24, p27

DOI: 10.3233/CBM-170234

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 513-519, 2018

Authors: Li, Qicai | Song, Shirong | Ni, Guangzhen | Li, Yu | Wang, Xiaohui

Article Type: Research Article

Abstract: OBJECTIVE: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of osteosarcoma (OS); Previous study has reported that miR-542-3p was significantly upregulated in osteosarcoma tissues and miR-542-3p may be as an oncogene in osteosarcoma pathogenesis. In our study, we investigated the circulating miR-542-3p and its clinical relevance in osteosarcoma. METHODS: Serum MiR-542-3p levels were determined by quantitative real-time PCR assays (qRT-PCR) in 76 patients with OS and 76 healthy volunteers. Patient survival analyses were …performed by Kaplan-Meier analyses and Cox regression models. All statistical tests were two-sided. RESULTS: It was observed that the serum levels of miR-542-3p was significantly higher in patients with OS compared with the control groups (P < 0.01). High serum of miR-542-3p was significantly associated with advanced tumor stage and shorter survival (P < 0.01). ROC curve analysis calculated the ideal miR-542-3p cut-off value of 0.84 in prediction of OS, with a sensitivity of 53.8%, specificity of 93.6%, positive predictive value of 87.3% and negative predictive value of 63.7%. CONCLUSIONS: The results showed that serum miR-542-3p levels could serve as a non-invasive blood biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients. Show more

Keywords: Osteosarcoma, biomarker, prognosis, miR-542-3p

DOI: 10.3233/CBM-170255

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 521-526, 2018

Authors: Bao, Jie | Zhou, Chenjie | Zhang, Jiaqing | Mo, Jiaqiang | Ye, Qing | He, Junming | Diao, Jingfang

Article Type: Research Article

Abstract: BACKGROUND: The long non-coding RNA FOXD2-AS1 is highly expressed in non-small cell lung cancer and promotes malignant progression. However, the role of FOXD2-AS1 in esophageal squamous cell carcinoma (ESCC) is still unclear. OBJECTIVE: In this study, we examined the relationships between the expression level of FOXD2-AS1 and the outcome of ESCC patients. METHODS: Expression of FOXD2-AS1 was evaluated in cancer tissue and adjacent non-tumor tissue samples from 147 ESCC patients who received radical surgical resection using qRT-PCR. The correlations between the expression level of FOXD2-AS1 and patients’ overall (OS) and disease free survival …(DFS) were analyzed. RESULTS: FOXD2-AS1 expression was upregulated in ESCC tissue than that in adjacent non-tumor tissue samples (P < 0.001). Kaplan-Meier analysis showed that high FOXD2-AS1 expression was correlated with poor prognosis in ESCC patients. Patients with a high level of FOXD2-AS1 had a shorter OS and DFS than those with a low level of FOXD2-AS1 (P = 0.005 and 0.0001, respectively). On multivariate analysis, the hazard ratio of FOXD2-AS1 expression was 1.66 (95% CI = 1.04–2.64, P = 0.033) for OS and 2.68 (95% CI = 1.49–4.82, P = 0.001) for DFS. CONCLUSIONS: Overall, our results provided convinced evidence that FOXD2-AS1 may serve as a predictive marker for ESCC patients’ survival. Show more

Keywords: Long non-coding RNA, FOXD2-AS1, survival, esophageal squamous cell carcinoma

DOI: 10.3233/CBM-170260

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 527-533, 2018

Authors: Xiong, Jie | Xiong, Ke | Bing, Zhitong

Article Type: Research Article

Abstract: BACKGROUND: Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with urothelial bladder cancer (UBC), and many genes have been found to be associated with UBC prognosis. PURPOSE: The objective of this study is to develop a signature which integrates clinical and molecular information to predict the overall survival of UBC patients more accurate. MATERIALS AND METHODS: We integrated messenger RNA (mRNA) and microRNA (miRNA) expression profiles and the corresponding clinical data of 402 UBC patients and 19 normal controls from The Cancer Genome Atlas. Univariate …Cox regression followed by a multiple testing correction and an elastic net-regulated Cox regression were adopted to identify a prognostic signature. RESULTS: We generated an integrated clinical-RNA signature which consisting of 3 clinical variables, 3 protective mRNAs, 7 risky mRNAs, 2 protective miRNAs and 1 risky miRNA. The area under the receiver operating characteristic curve of the integrated clinical-RNA signature was 0.802, larger than that of the clinical-alone signature (0.709) or the RNA-alone signature (0.726). UBC patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (clinical-RNA signature, hazard ratio = 2.441). CONCLUSIONS: Our conclusions that we have identified an integrated clinical-RNA signature that was superior to the traditional clinical-alone signature for ascertaining the overall survival prognosis of patients with UBC. These findings provide some novel genes for tumor molecular biologist to further study their functions and mechanisms in UBC tumorigenesis and malignance, and may be useful for effective clinical risk management of UBC patients. Show more

Keywords: Urothelial bladder cancer, clinical, RNA, signature, prognosis

DOI: 10.3233/CBM-170314

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 535-546, 2018

Authors: Guo, Xiangjun | Shi, Jiaxin | Wen, Yan | Li, Mengmeng | Li, Qin | Li, Xiaomei | Li, Jiashu

Article Type: Research Article

Abstract: BACKGROUND: High-mobility group A2 (HMGA2) has been investigated to be associated with tumorigenesis; however, the expression pattern and clinical significance of HMGA2 in non-small cell lung cancer (NSCLC) remains poorly understood. The purpose of this study is to examine the expression of HMGA2 and to analyze its relationships with respect to clinico-pathological features and patient survival in NSCLC. METHODS: The expression level of HMGA2 was examined by Western blot and immunohistochemistry in NSCLC cells and tissues. The relationship between HMGA2 expression and survival of NSCLC patients was calculated by a Kaplan-Meier method and the evaluation of …risk factor was determined by the multiple regression analysis. RESULTS: NSCLC tissues exhibited a higher expression level of HMGA2 compared to normal tissues (p < 0.05) and the expression level of HMGA2 was significantly associated with poor differentiation of NSCLC (p < 0.05), lymph node metastasis (p < 0.05) and advanced clinical stage (p < 0.05). Besides, HMGA2 was also confirmed to be elevated in NSCLC cells by Western blot. Moreover, increased expression of HMGA2 correlated with decreased survival of NSCLC patients (p < 0.05). CONCLUSIONS: HMGA2 was highly expressed in NSCLC tissues and cells and its overexpression was correlated with low-grade differentiation, lymph node metastasis, advanced clinical stage and poor survival time of NSCLC, which suggested that it could serve as a potential molecular marker and prognostic index for NSCLC. Show more

Keywords: Non-small cell lung cancer, NSCLC, high-mobility group A2, HMGA2, expression, prognosis

DOI: 10.3233/CBM-170401

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 547-555, 2018

Authors: Guan, Zhen-Biao | Cao, Yu-Shu | Li, Yi | Tong, Wan-Ning | Zhuo, An-Shan

Article Type: Research Article

Abstract: BACKGROUND: The aim in this study was to explore the role of long non-coding RNA GHET1 in development of non small cell lung cancer (NSCLC). METHODS: LncRNA GHET1 expression levels were analyzed by qRT-PCR in tumor tissues and adjacent normal tissues in NSCLC. Measuring the cell proliferation and invasion abilities by CCK8, cell colony formation and transwell invasion assays. Relative protein expression was analyzed by western blot assays. RESULTS: Expression of lncRNA GHET1 was notably higher in NSCLC tissues compared with adjacent normal tissues by using qRT-PCR analyses. Higher lncRNA GHET1 expression associated …with lymph node metastasis, TNM stage and showed poor outcome in NSCLC patients. Knockdown of lncRNA GHET1 suppressed cell proliferation and invasion capacity and Epithelial-Mesenchymal Transition (EMT) phenomenon of NSCLC cells. Moreover, we demonstrated that knockdown of lncRNA GHET1 suppresses LATS1/YAP pathway signaling pathway by downregulating YAP1 expression in NSCLC cells. CONCLUSIONS: GHET1 predicted a poor outcome and acted as a tumor-promoting gene in NSCLC. Thus, inhibition of GHET1 may be a potential target of NSCLC treatment. Show more

Keywords: Non small cell lung cancer, long non-coding RNA, GHET1, cell proliferation, cell invasion

DOI: 10.3233/CBM-170431

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 557-563, 2018

Authors: Duan, Shujie

Article Type: Research Article

Abstract: OBJECTIVE: To explore the influence of Beclin-1 on vasculogenic mimicry (VM) induced by hypoxia in glioma. METHODS: CD34-PAS staining was carried out to observe VM formation, and immunohistochemistry was used to determine the expression levels of Beclin-1, HIF-1α , VEGF and MMP2 in 105 patients with primary glioma. Human glioma U87MG cells were divided into Normoxia, Hypoxia, Hypoxia + NC siRNA and Hypoxia + Beclin-1 siRNA groups. Cobalt chloride (CoCl 2 ) was used to stimulate hypoxic conditions, and a VM tube formation assay …was used to detect VM formation. Wound healing and Transwell invasion assays were used to detect the invasive and migratory abilities of U87MG cells, respectively. Fluorescent LC3 puncta analysis was performed to examine the status of autophagic flux. Expression levels of Beclin-1 and VM-related molecules were determined using real-time quantitative-polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: There were 34 VM-positive cases and 71 VM-negative cases among 105 glioma patients, and VM formation was correlated with pathological grade and the expression of Beclin-1, HIF-1α , VEGF and MMP2. Positive relations were found between Beclin-1 and the expression of HIF-1α , VEGF and MMP2. Under hypoxic conditions, significant increases in the total length of tubes, migration rate, invasion cell number and expression of VM-related molecules were found in U87MG cells. Silencing Beclin-1 markedly decreased hypoxia-induced VM formation and the invasive and migratory abilities, together with the expression of VM-related molecules, in U87MG cells and significantly inhibited the autophagic flux. CONCLUSION: Silencing Beclin-1 can attenuate hypoxia-induced VM formation and the metastatic ability of U87MG cells and is a potential target for VM inhibition in glioma. Show more

Keywords: Beclin-1, glioma, vasculogenic mimicry, siRNA

DOI: 10.3233/CBM-170444

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 565-574, 2018

Authors: Zhang, Hai-Feng | Li, Wei | Han, Yi-Di

Article Type: Research Article

Abstract: BACKGROUND: Recent findings have identified thousands of long non-coding RNAs (lncRNAs) and reveal that lncRNAs play crucial roles in the regulation of tumor development and progression. However, the clinical significance and potentially functional value of LINC00261 in hepatocellular carcinoma (HCC) remain unknown. METHODS: Expression of LINC00261 was detected by qRT-PCR in HCC tissues and adjacent normal tissues. Kaplan-Meier analysis was used to assess the relationship between LINC00261 expression and the overall survival (OS) time. Cell proliferation and invasion were evaluated using MTT assay, cell colony formation assay and transwell assay. The protein expression was determined by …western blot analysis. RESULTS: In present study, we confirmed that LINC00261 was frequently lower in HCC tissues compared to adjacent normal tissues. Decreased LINC00261 expression associated with lager tumor size, TNM stage (III-IV) and poor overall survival time of HCC patients. The functional assays demonstrated that overexpression of LINC00261 in HCC cells inhibited cell proliferation, cell colony formation, cell invasion and EMT process in vitro . Moreover, we also demonstrated that upregulation of LINC00261 significantly inhibited Notch signaling by downregulating Notch1 and Hes-1 expression in HCC cells. CONCLUSION: These results indicated that LINC00261 may be a potential target of HCC treatment. Show more

Keywords: Hepatocellular carcinoma, long non-coding RNA, LINC00261, Notch1, Hes-1

DOI: 10.3233/CBM-170471

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 575-582, 2018