Cancer Biomarkers - Volume 15, issue 5

Authors: Zheng, Haiyan | Ruan, Jian | Zhao, Peng | Chen, Shiping | Pan, Linglan | Liu, Jianqiao

Article Type: Research Article

Abstract: Heparanase(HPSE), an endo-β -D-glucuronidase, is found overexpressed in Ovarian cancer (OC). The purpose of our work was to investigate primitively the possible role of HPSE in the development of OC. In this study, RNA interference (RNAi) with a HPSE small hairpin RNAs(HPSE-shRNA) and plasmid with HPSE were used to identify the effects of HPSE on the regulation of malignant behaviors of OC. OV-90 and SKOV3 were selected as a cell model in vitro and in vivo . The results showed that down-regulation of HPSE can significantly inhibit the proliferative and invasive ability of SKOV3 cells, and up-regulation of HPSE …in OV-90 cells showed the opposite effects. Compared with the parental OC cells, HPSE silencing cells exhibited attenuated capacities in developing tumor in nude mice, while the growth tumors xenografts derived from these cells were dramatically regressed. In conclusion, our results suggest that HPSE contributes to the proliferation and metastasis of OC and HPSE might be a potent molecular target for OC treatment. Show more

Keywords: Ovarian cancer, heparanase, invasion, proliferation

DOI: 10.3233/CBM-150459

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 525-534, 2015

Authors: Wu, Z.Y. | Wang, S.M. | Chen, Z.H. | Huv, S.X. | Huang, K. | Huang, B.J. | Du, J.L. | Huang, C.M. | Peng, L. | Jian, Z.X. | Zhao, G.

Article Type: Research Article

Abstract: BACKGROUND: Analysis using publicly available algorithms has found that high mobility group AT-hook 2 (HMGA2), a key transcriptional regulatory factor, is a potential target of microRNA-204 (miR-204). Some studies have shown that both miR-204 and HMGA2 are associated with cancer development. OBJECTIVE: We examined the possible relationship between miR-204 and HMGA2 in the development of thyroid cancer. METHODS: We assessed miR-204 expression in thyroid cancer specimens and cell lines using real-time polymerase chain reaction (PCR). Luciferase reporter assay was used to confirm the target associations. The effect of miR-204 on cell proliferation was confirmed …with tetrazolium and colony formation assays. Gene and protein expression were examined using real-time PCR and western blotting, respectively. RESULTS: MiR-204 was downregulated in the thyroid cancer specimens and cell lines, and targeted the 3^\prime untranslated region of HMGA2 directly. MiR-204 overexpression decreased cyclin D1 and Ki67 expression and increased P21 expression, which subsequently inhibited thyroid cancer cell proliferation. CONCLUSIONS: Our findings suggest that miR-204 plays a protective role by inhibiting thyroid cancer cell proliferation, and may identify new targets for anti-cancer treatment. Show more

Keywords: MiR-204, HMGA2, proliferation, thyroid cancer

DOI: 10.3233/CBM-150492

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 535-542, 2015

Authors: Wang, Tao | Ji, Feng | Dai, Zhitang | Xie, Yue | Yuan, Dongtang

Article Type: Research Article

Abstract: BACKGROUND: MicroRNA (miR)-191 has been observed to be overexpressed in osteosarcoma cell lines in comparison with osteoblasts. OBJECTIVE: To investigate the clinical significance of miR-191 in human osteosarcomas. METHODS: Quantitative PCR was performed to detect miR-191 expression in osteosarcoma tissues and patients' sera. RESULTS: miR-191 expression levels, both in osteosarcoma tissues and patients' sera, were significantly higher than those in matched adjacent normal bone tissues and healthy controls (both P< 0.001). Importantly, miR-191 could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.808). Then, high serum …miR-191 expression was significantly associated with advanced clinical stage (P= 0.001), large tumor size (P= 0.01) and positive distant metastasis (P= 0.001). Moreover, overall and disease-free survival durations in patients with high miR-191 expression were both shorter than those with low miR-191 expression. Multivariate analysis further identified serum miR-191 level as an independent and significant prognostic factor for both overall survival (P= 0.01) and disease-free survival (P= 0.02). CONCLUSIONS: Our data provide new insights for the involvement of miR-191 in osteosarcoma and suggest that the increased expression of miR-191 may be associated with aggressive tumor progression and adverse outcome. Of note, serum miR-191 quantification may be a promising biomarker for the diagnosis and prognosis in osteosarcoma. Show more

Keywords: Osteosarcoma, serum, microRNA-191, diagnosis, prognosis, real-time quantitative RT-PCR

DOI: 10.3233/CBM-150493

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 543-550, 2015

Authors: Gul, Summer | Murad, Sheeba | Ehsan, Naureen | Bloodsworth, Peter | Sultan, Aneesa | Faheem, M.

Article Type: Research Article

Abstract: BACKGROUND: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor beta (TGF-β) super family, which are primarily known for their inherent role in osteogenesis and ontogenesis. Accumulating evidence suggests the regulatory role of BMP-4 in cellular proliferation, apoptosis, differentiation and thus a possible oncogenic role. OBJECTIVE: Variable cellular expression and in vitro functional assays are indicative of the involvement of BMP related signaling in Breast cancer (BC). The differential expression of BMP-4 in the peripheral blood of BC patients may therefore be considered as a potential biomarker. Therefore, this study aimed to evaluate transcriptional …expression of BMP-4 and its cognate receptor BMPR-II in the peripheral blood from the BC patients in relation to the healthy individuals. METHODS: The expression pattern of BMP-4 and BMPR-II was analyzed in the blood of breast cancer patients (n= 22) and healthy controls (n= 22) through Semi Quantitative Reverse transcription Polymerase chain reaction. RESULTS: An up-regulated expression of BMP-4 and BMPR-II was observed in the peripheral blood of breast cancer patients especially in the advanced-stage of the disease. Moreover, BMP-4 and BMPR-II expressions were found to be correlated. CONCLUSION: The current preliminary results based on the transcriptional analysis suggest the prospective use of BMP4 as a biomarker, however further validation is required. Show more

Keywords: BMP-4, BMPR-II, breast cancer (BC), RT-PCR, Peripheral blood mononuclear cells (PBMCs)

DOI: 10.3233/CBM-150494

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 551-557, 2015

Authors: Erkut, Nergiz | Mentese, Ahmet | Ozbas, Hasan Mucait | Sumer, Aysegul | Orem, Asım | Topbas, Murat | Sonmez, Mehmet

Article Type: Research Article

Abstract: BACKGROUND: Hypoxia plays an important role in the development and progression of hematologic malignancies. OBJECTIVE: This study was intended to investigate the effectiveness of ischemia-modified albumin (IMA) for demonstrating hypoxia in patients with acute leukemia. METHODS: Blood specimens were collected from 132 subjects (44 acute leukemia patients, 40 iron deficiency anemia (IDA) patients and 48 healthy controls). Serum levels of IMA and malondialdehyde (MDA) were analyzed using conventional methods. RESULTS: Serum levels of IMA were higher in patients with acute leukemia than in those with IDA and healthy controls (acute leukemia patients; …0.69 ± 0.14 ABSUs, IDA patients; 0.61 ± 0.09 ABSUs, controls; 0.50 ± 0.09 ABSUs, respectively). There was a negative correlation between serum IMA levels and hemoglobin (Hb) values (r = - 0.312) and between serum IMA levels and hematocrit (Hct) values, (r = - 0.305) in patients with acute leukemia. Serum levels of MDA were higher in patients with acute leukemia than in those with IDA. But there was no difference in patients with acute leukemia and IDA compared to healthy controls (acute leukemia patients; 2.23 ± 1.82 nmol/mL, IDA patients; 1.36 ± 0.94 nmol/mL, healthy controls; 1.79 ± 0.78 nmol/mL, respectively). CONCLUSIONS: IMA can be effective for demonstrating hypoxia in patients with acute leukemia. Show more

Keywords: Ischemia-modified albumin, acute leukemia, hypoxia

DOI: 10.3233/CBM-150495

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 559-565, 2015

Authors: Hou, Ya-Chao | Deng, Jing-Yu | Zhang, Ru-Peng | Xie, Xing-Ming | Cui, Jing-Li | Wu, Wei-Peng | Hao, Xi-Shan | Liang, Han

Article Type: Research Article

Abstract: OBJECTIVE: To elucidate the clinical significance of the methylated status of CpG site count of PCDH10 promoter in the survival prediction in gastric cancer (GC). METHODS: In the previous study, we demonstrated that the methylated CpG site count was significantly associated with the overall survival (OS) of GC patients by using the bisulfite genomic sequencing (BGS) with no less than five clones per sample. It was so complex and expensive for patients to undergo the BGS clones. In this study, we detected the different CpG site counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC …samples of 471 patients by directly bisulfite genomic sequencing (D-BGS) without any clone. Furthermore, we evaluated the relationships between the methylated status of PCDH10 promoter and OS. RESULTS: Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to present with PCDH10 promoter methylation by D-BGS. Patients who presented with 5 or more methylated CpG site counts of PCDH10 promoter had significantly poorer prognosis than patients who with less than 5 methylated CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival analysis, we demonstrated that T stage, N stage and the hypermethylated CpG site counts of PCDH10 DNA promoter were the independent predictors of OS of GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA promoter had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other two independent predictors of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA promoter as the best prognostic predictor of GC. CONCLUSIONS: Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS. Show more

Keywords: PCDH10, methylation, direct bisulfite genomic sequencing, prognosis, gastric cancer

DOI: 10.3233/CBM-150496

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 567-573, 2015

Authors: Jakubauskienė, Eglė | Peciuliene, Inga | Vilys, Laurynas | Mocevicius, Paulius | Vilkaitis, Giedrius | Kanopka, Arvydas

Article Type: Research Article

Abstract: BACKGROUND: Cell lines derived from human tumors have been extensively used as experimental models of neoplastic disease. Although such cell lines differ from both normal and cancerous tissue. OBJECTIVE: The data obtained used DNA and RNA microarray systems does not give full information about protein expression levels in cells and tissues. We present experimental evidence that splicing factor SRSF1, SRSF2, U2AF35, U2AF65 and KHSRP expression levels in gastrointestinal tract (colon, gastric and pancreatic) tumors differ compare to healthy tissues and in cell lines, derived from corresponding organs. METHODS: Protein expression was analyzed using Western …blots. RT-PCR method was used for Fas and Rac splicing analysis. RESULTS: Obtained results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumors in vivo . Expression levels of individual splicing factors in tumors might serve as tumor markers. Not all experimental results obtained from cell lines reflect changes that occur in tumors. Also Fas and Rac, cancer associated genes, tumor associated sFas and Rac1b mRNA isoform profiles in cell lines do not correspond to profiles that are observed in tumors. CONCLUSIONS: Not all experimental results obtained in cell lines reflect changes that occur in real tumors. Show more

Keywords: Tumor, colon, gastric, pancreatic, splicing factor, Fas, Rac, mRNA, cell lines, SR proteins

DOI: 10.3233/CBM-150497

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 575-581, 2015

Authors: Masood, Nosheen | Mubashar, Aroosha | Yasmin, Azra

Article Type: Research Article

Abstract: BACKGROUND: GSTM1 and GSTT1 are phase II enzymes which provide chemical defense to cells. OBJECTIVE: This study was designed to evaluate association of GSTM1 and GSTT1 deletion along with epidemiological factors with risk of colon and rectum cancers. METHODOLOGY: Multiplex PCR was used for cancer patients as well as age and gender matched cancer free controls. RESULTS: Mean age of patients and controls was 45.5 (± 14.6) and 43.5 (± 18.08) years respectively. Among epidemiological factors; gender, age ≥ 50 years, active/passive smoking, naswar addiction, residential area, family history, red meat, fruit …and vegetable intake showed no association with CRC (P ≥ 0.05). Symptoms of CRC like altered bowel habits (70%) was more common compared with other symptoms. GSTM1 (P ≤ 0.05) and GSTT1 (P ≤ 0.05) deletions were found to be significantly associated with CRC compared with controls. Association of epidemiological factors like gender, active/passive smoking, naswar addiction, residential area and family history were associated neither with GSTM1 deletion nor to GSTT1 deletion in both cancers (P ≥ 0.05). Significant association was present between stage III and GSTM1 (CI 95% 0.15-1.39) as well as GSTT1 (CI 95% 0.14-2.44) deletion in CRC. CONCLUSION: These results suggest that GSTM1 and GSTT1 deletion were associated with increased risk of colon and rectum cancer in Pakistani population. Show more

Keywords: GSTM1, GSTT1, epidemiology, colon cancer, rectum cancer

DOI: 10.3233/CBM-150498

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 583-589, 2015

Authors: Song, Yan | Liu, Dan | He, Guoping

Article Type: Research Article

Abstract: BACKGROUND: The significance of transketolase-like enzyme 1 (TKTL1) and p63 in the clinical progression and prognosis of gastric cancer patients has not been established. OBJECTIVE: This study investigated the expression of TKTL1 and p63 in gastric cancer and their clinical significance. METHODS: TKTL1 and p63 expression in 101 gastric cancer tissue specimens and 25 normal gastric mucosa tissues were detected by immunohistochemistry (IHC). RESULTS: The percentage of positive TKTL1 and p63 expression in gastric carcinomas was significantly higher than that in normal gastric mucosa tissues (P < 0.05). Positive TKTL1 and p63 …expression significantly correlated with larger tumor size, deeper invasion, higher TNM stage, and lymph node metastasis (P< 0.05). The expression of TKTL1 significantly correlated with p63 expression in gastric cancer tissues (r = 0.476, P < 0.01). Univariate analysis revealed that positive TKTL1 and/or positive p63 expression correlated significantly with shorter survival and lower 5-year survival rate (P = 0.001). Cox multivariate analysis demonstrated that expression of TKTL1 and p63 is an independent prognostic factor (P < 0.05) in gastric cancer. CONCLUSIONS: Both TKTL1 and p63 are independent prognostic factors of the poor outcome of gastric cancer patients. Show more

Keywords: TKTL1, p63, gastric cancer, prognosis

DOI: 10.3233/CBM-150499

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 591-597, 2015

Authors: Bai, Juanjuan | Zhang, Zhongling | Li, Xing | Liu, Huifan

Article Type: Research Article

Abstract: OBJECTIVE: The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. METHODS: We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. RESULTS: MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis …and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo . We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. CONCLUSION: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM. Show more

Keywords: Malignant melanoma (MM), neuropilin1 (NRP1), miR-365, invasion and metastasis, pathogenesis, target therapy, cancer biomarker

DOI: 10.3233/CBM-150500

Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 599-608, 2015