Cancer Biomarkers - Volume 15, issue 6

Authors: Li, Hai | Zhou, Xin | Zhu, Jun | Cheng, Wenfang | Zhu, Wei | Shu, Yongqian | Liu, Ping

Article Type: Research Article

Abstract: BACKGROUND: MiR-4728 was recently identified to be related with HER2 in several cell lines and limited tissue samples. OBJECTIVE: To investigate whether miR-4728 could predict HER2 status in a larger cohort. METHODS: The expression of miR-4728-3p and miR-4728-5p was identified in breast cancer (BC) and gastric cancer (GC) tissues with different HER2 status using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). An additional 22 plasma samples was investigated to explore the potential application of miR-4728 as a non-invasive biomarker in predicting HER2 status. RESULTS: MiR-4728-3p and …miR-4728-5p were significantly up-regulated in HER2-positive patients compared with HER2-negative patients. Compared with the expression in adjacent normal tissues, miR-4728-3p and miR-4728-5p were both elevated in HER2-negative and HER2-positive GC tissues but only miR-4728-3p in HER2-positive BC tissues. Further analyses revealed that miR-4728-3p had greater ability than miR-4728-5p in discriminating subgroups with different intensity of HER2 staining in both BC and GC patients. In addition, miR-4728-3p but not miR-4728-5p was significantly up-regulated in plasma of BC patients with positive HER2. CONCLUSIONS: MiR-4728-3p had better ability in distinguishing patients with different status of HER2 than miR-4728-5p. And plasma miR-4728-3p might act as a non-invasive biomarker in predicting HER2 status. Show more

Keywords: miR-4728, marker, HER2

DOI: 10.3233/CBM-150524

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 807-814, 2015

Authors: Lee, Yu-Ting | Liu, Hsueng-Mei | Lee, Li-Hsuan | Liu, Chia-Jen | Lin, Jeong-Shi | Chao, Ta-Chung | Tzeng, Woan-Fang | Chiou, Tzeon-Jye

Article Type: Research Article

Abstract: BACKGROUND: The polymorphic CAG repeats of the androgen receptor (AR) gene have been suggested to affect the risk of breast cancer, but the results are controversial. In addition, the relationship between patients' CAG genotype and the prognosis has not been investigated. OBJECTIVE: The purpose of this study is to access the association between the polymorphic CAG repeats and the incidence and prognosis of breast cancer. METHODS: One hundred and fifty-six breast cancer cases and 108 healthy controls from Taipei Veteran General Hospital were enrolled. The length of CAG repeats was analyzed among by means …of PCR amplification. The logistic regression model was used for cross-sectional analyses of prevalent breast cancer. Furthermore, we categorized the cases according to the average length of both CAG alleles (CAGn ≥ 23 versus < 23). Outcomes were disease-free survival and mortality. The Cox proportional hazards model and Kaplan-Meier estimate were used for survival analysis. RESULTS: The median age was 56 (51-64) and 46 (37-52) in breast cancer patients and healthy controls, respectively. The median of CAGn was 22.5 (21.5-24) in study group and 23 (21.5-24) in controls. Our study showed the length of CAG repeats did not contribute to breast cancer or benign breast tumors (HR 1.01; 95% CI, 0.90-1.13). In the median follow-up of 6.59 years, we found the CAGn ≥ 23 (n = 75) could be a poor prognosis (adjust HR, 3.08; 95% CI, 1.42-6.67, p = 0.004). CONCLUSION: The CAG polymorphism is not associated with development of breast cancer, but patients with more CAG repeats of the AR gene are prone to poor prognoses. Show more

Keywords: Prognostic factor, CAG repeat, CAG polymorphism, androgen receptor, breast cancer

DOI: 10.3233/CBM-150525

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 815-822, 2015

Authors: He, Qingqing | Peng, Bo | Zhuang, Dayong | Xiao, Lei | Zheng, Luming | Fan, Ziyi | Zhu, Jian | Xu, Benmei | Xu, Cheng | Zhao, Jiangman | Wu, Liming | Zhou, Peng | Hou, Lei | Yu, Fang | Zhao, Guowei

Article Type: Research Article

Abstract: BACKGROUND: The molecular classification of breast cancer mainly focuses on estrogen receptor (ER), Progesterone receptor (PgR), and Human Epidermal Growth Factor Receptor 2(HER2/Neu) status detected by immunohistochemistry (IHC) analysis. The β -tubulin isotype III (TUBB3) gene was thought to be a marker of taxane resistance or cancer aggressiveness. METHODS: To evaluate the clinicopathological significance of TUBB3 expression in breast cancer patients, we measured TUBB3 mRNA levels in 92 breast cancer patients by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and examined their correlation with ER, PgR, and HER2 status detected by IHC. RESULTS: We observed …a significant positive correlation between the TUBB3 mRNA expression and the immunohistochemical positivity of both PgR (p= 0.000) and HER2 (p= 0.001). In addition, TUBB3 mRNA expression was associated with lymph nodes status (P= 0.008) and tumor stages (0.029), but no correlation was found with other clinicopathological features, such as age, pathohistological grades and tumor size. CONCLUSIONS: In conclusion, TUBB3 expression correlated significantly with molecular markers of breast cancer, such as PgR and HER2, suggesting that TUBB3 mRNA level facilitate the identification of a subset of patients who respond to Taxane treatment in addition to hormonal therapy and trastuzumab. Show more

Keywords: Breast cancer, ER, PgR, HER2, β -tubulin isotype III

DOI: 10.3233/CBM-150526

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 823-831, 2015

Authors: Chen, Guo-Hui | Xue, Qian-Qian | Li, Jun | Gao, Tian-Le | Sun, Qing-Shun | Bai, Guang-Ping

Article Type: Research Article

Abstract: AIMS: To clone and express Siva1 protein, and to investigate the role of Siva1 protein in proliferation, apoptosis, invasion, and migration of human nasopharyngeal carcinoma cell line CNE-2 in vitro and in vivo . METHODS: The PCR fragment of Siva1 from human nasopharyngeal carcinoma cell line CNE-2 were double digested with BamHI and SalI and then induced into the pQE30 vector double digested by the same enzymes. The pQE30 vector harboring Siva1 was introduced into M15 competent cells and then induced by isopropyl β -D-1-thiogalactopyranoside (IPTG). The Siva1 fusion protein was identified by 12% sodium …dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and then separated and purified by Ni-affinity chromatography. Subsequently, the effects of recombinant Siva1 protein on proliferation, apoptosis, invasion and migration were assayed in vitro and in vivo . RESULTS: The transformed cells expressed Siva1 fusion protein with a molecular weight of approximately 12 kDa. Cell counting kit-8 (CCK-8) assay showed that the Siva1 protein significantly inhibited the proliferation of the CNE-2 cells at a concentration of 10 μ mol/L. In addition, compared to the control, the Siva1 protein promoted the apoptosis of the cancer cells. And, the Siva1 protein greatly suppressed the invasion and migration of the cancer cells. In vivo , the Siva1 protein significantly inhibited the tumor growth of the tumor-bearing mice. Further, the Siva1 treatment markedly upregulated Bax, caspase-3, and downregulated Bcl-2 protein levels in the transplanted tumor tissue. CONCLUSIONS: The Siva1 protein has a significant anticancer activity on human nasopharyngeal carcinoma cell line CNE-2 including inhibiting proliferation, invasion, migration and promoting apoptosis of the cancer cells. Show more

Keywords: Siva1, nasopharyngeal carcinoma, proliferation, invasion, migration

DOI: 10.3233/CBM-150527

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 833-841, 2015

Authors: Aravantinos, G. | Isaakidou, A. | Karantanos, T. | Sioziou, A. | Theodoropoulos, G.E. | Pektasides, D. | Gazouli, M.

Article Type: Research Article

Abstract: BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients …receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity. Show more

Keywords: Colorectal cancer, bevacizumab, CD133 polymorphisms

DOI: 10.3233/CBM-150528

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 843-850, 2015

Authors: Ayremlou, Nooshin | Mozdarani, Hossein | Mowla, Seyed Javad | Delavari, Alireza

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs can function as oncogenes and tumor suppressor genes in human cancers. The expression of miR-107 is high in various types of solid tumors. OBJECTIVE: The aim of this study was to evaluate the tumor and serum level of miR-107 and its correlation to HIF-1α expression in gastric cancer patients. METHODS: Quantitative real-time PCR was used to analyze the expression of miR-107 and HIF-1α in 36 pairs of fresh gastric cancer and matched adjacent normal tissue specimens and the serum of these patients compared to age matched controls. RESULTS: …The expression level of miR-107 was significantly higher in tumor tissues compared to adjacent normal tissue (p= 0.04). For serum, the expression level of miR-107 was significantly higher in gastric cancer patients than in age matched controls (p= 0.04). The correlation between tumor and serum expression of miR-107 with tumor hypoxia was found to be significant (p≤ 0.001). CONCLUSION: The overexpression of miR-107 in tumors and serum of gastric cancer patients and its correlation with HIF-1α expression in tumor tissues was indicated that miR-107 may have a potential to use as a biomarker for detection of gastric cancer patients and hypoxia in gastric cancer tumor. Show more

Keywords: Gastric cancer, miR-107, hypoxia

DOI: 10.3233/CBM-150529

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 851-860, 2015

Authors: Askeland, Eric J. | Chehval, Vincent A. | Askeland, Ryan W. | Fosso, Placede G. | Sangale, Zaina | Xu, Nafei | Rajamani, Saradha | Stone, Steven | Brown, James A.

Article Type: Research Article

Abstract: BACKGROUND: The outcome of surgically resected, apparently localized, clear cell renal carcinoma (ccRCC) is uncertain. OBJECTIVE: To evaluate if cell cycle progression (CCP) gene expression can predict future metastasis. METHODS: Pathologic T2a-T3b tumors at University of Iowa were reviewed. Patients with known or suspected metastasis, lymph node involvement or who received neoadjuvant or adjuvant radiation, chemotherapy or immunotherapy were excluded. Case and control cohorts were defined as those who did or did not develop metastatic disease within 5 years. Measured levels of 31 cell cycle genes and 15 control genes from the tumor …were calculated as a CCP score. Additionally, gene expression data for a separate ccRCC cohort was downloaded from The Cancer Genome Atlas (TCGA). RESULTS: Univariate analysis of 26 cases and 38 controls revealed that the CCP score predicted progression to metastasis (OR 2.65, p = 0.0091). In multivariate logistic regression modeling, CCP expression remained a significant independent predictor for progression (p = 0.026). The CCP score was also significantly associated with distant metastasis in the TCGA renal cancer cohort in both univariate (p = 1.0 × 10-9 ) and multivariate (p = 5.6 × 10-3 ) analysis. CONCLUSION: The CCP score has prognostic value in predicting metastatic progression after resection of organ-confined ccRCC. Show more

Keywords: Clear cell renal cell carcinoma, kidney cancer, metastasis, biological markers

DOI: 10.3233/CBM-150530

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 861-867, 2015

Authors: Amara, Sameh | Chaar, Ines | Khiari, Meriem | Ounissi, Donia | Weslati, Marwa | Boughriba, Rahma | Hmida, Abdelmajid B. | Bouraoui, Saadia

Article Type: Research Article

Abstract: BACKGROUND: Recent studies suggest that SDF-1 and CXCR4 are expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis. However, the pathophysiological significance of their expression in colorectal cancer (CRC) tissue has not been fully elucidated. OBJECTIVE: The purpose of this study was to assess SDF-1/CXCR4 expression and to explore its contribution to colorectal cancer. METHODS: We examined SDF-1 and CXCR4 mRNA expression in 124 primary colorectal tumour and 35 liver metastases tissues and matched adjacent noncancerous tissues by reverse transcriptase PCR (RT-PCR). Furthermore, their …expression was analyzed by immunohistochemistry. The relationship between SDF-1/CXCR4 expression and clinicopathological features were analyzed by appropriate statistics. X2 test and Kaplan-Meier analysis were used to investigate the correlation between the ligand-receptor expression and prognosis of colorectal cancer patients. RESULTS: The relative mRNA expression of SDF-1 and CXCR4 was significantly elevated in colorectal cancer tissues as compared with adjacent noncancerous tissues (P < 0.001). The high expression of proteins expression in colorectal cancer tissues was significantly correlated with tumor grade (P = 0.0001), clinical stage (P < 0.05), and lymphatic invasion (P < 0.05). Furthermore, patients with CXCR4 nuclear-type expression showed more frequent lymph node metastasis (p = 0.021), advanced clinical stage (p = 0.001) and lymphatic invasion (p = 0.03) than those with cytoplasm staining-type. Kaplan-Meier survival analysis revealed that high expression of the couple SDF-1/CXCR4 correlated with poor prognosis of colorectal cancer patients (P < 0.001). CONCLUSION: SDF-1 and CXCR4 may play an important role in the progression of colorectal cancer. The present data suggest that there is a significant association between SDF-1/CXCR4 to enhance the liver metastases causing poor prognosis. Those proteins may potentially be used as an independent biomarker for the prognostic evaluation of colon cancer in the Tunisian cohort. Show more

Keywords: Colorectal cancer, chemokineschemokines receptor, liver metastases

DOI: 10.3233/CBM-150531

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 869-879, 2015

Authors: Li, Yongqing | Xu, Yadong | Yu, Chundong | Zuo, Wenshu

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs (miRNA) expression profiles might be useful novel biomarkers for tumor diagnostic and histological characterization. OBJECTIVE: Associations of miR-146 expression and breast cancer in very young women needed to be elucidated. METHODS: We investigated expressions of miR-146a, miR-146b and IL-6 in tissues between 120 young women with primary breast cancer and 130 patients with breast fibroadenoma by RT-PCR. The associations between the expression of miR-146, IL-6 and clinical parameters of breast cancer were analyzed. RESULTS: Levels of miR-146a and miR-146b in breast cancer tissues were lower while level of …IL-6 was higher compared to the fibroadenoma tissues and pericancerous breast tissues (P< 0.05). Positive associations were found between levels of miR-146a/b and IL-6 in breast cancer tissues and ER-PgR-, HER2/neu -, Ki-67 index ≥ 20%, tumor size > 2 cm, positive distant metastasis and lymph node metastasis, advanced clinical TNM stages (III-IV) and basal-like phenotype (P< 0.05). CONCLUSION: Down-regulations of miR-146a and miR-146b expression in breast tissues were related to development and deterioration of breast cancer. miR-146a and miR-146b might act as potential biomarkers for young women with breast cancer. Show more

Keywords: Breast cancer, miR-146a, miR-146b, RT-PCR

DOI: 10.3233/CBM-150532

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 881-887, 2015

Authors: Zheng, Chen-Guo | Chen, Rong | Xie, Jie-Bin | Liu, Chang-Bao | Jin, Zhao | Jin, Chun

Article Type: Research Article

Abstract: BACKGROUND: Activation of Notch and NF-κB signaling has been frequently observed in colorectal cancer (CRC) patients and contributes to the chemo-resistance and treatment failure. However, the relationship between these signaling pathways and CRC has not been clearly described. OBJECTIVE: To investigate the expression of Notch1, Jagged1, NF-κB and MMP-9 in CRC patients and analyze their correlation with clinicopathological factors. METHODS: Expression of Notch1, Jagged1, NF-κB and MMP-9 was visualized by immune-histology in the tumor tissue, adjacent and distant normal tissues from 47 CRC patients without receiving chemotherapy or radiotherapy. RESULTS: …Notch1 (80.8%), Jagged1 (80.8%), NF-κB (70.2%) and MMP-9 (76.6%) were overexpressed in cancer tissues compared normal tissues (P< 0.05). The intensity of Notch1, Jagged1 and NF-κB expression was associated with histological grading, depth of invasion, TNM staging and lymph node metastasis of CRC. MMP-9 was intimately correlated with depth of invasion, TNM staging and lymph node metastasis. NF-κB, MMP-9 and Notch1 expression was positively correlated (P< 0.05), and the same positive correlation was found among NF-κB, MMP-9 and Jagged1 expression (P< 0.05). CONCLUSION: Notch1, Jagged1, NF-κB and MMP-9 probably play a pivotal role during the CRC development, serving as biomarkers for early detection of the recurrence and metastasis and prognosis of CRC. Show more

Keywords: Colorectal cancer, notch, jagged, NF-κB, MMP-9

DOI: 10.3233/CBM-150533

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 889-897, 2015

Authors: Lian, Lian | Xia, You-You | Zhou, Chong | Shen, Xiao-Ming | Li, Xiang-Li | Han, Shu-Guang | Zheng, Yan | Mao, Zhong-Qi | Gong, Fei-Ran | Wu, Meng-Yao | Chen, Kai | Tao, Min | Li, Wei

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. China has a high incidence of gastric cancer. Inflammation is a critical component of tumor progression. It has been widely accepted that gastric cancer is an inflammation-driven cancer. In this study, we investigated the application value of systemic inflammatory response (SIR) markers, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR), in early diagnosis and prognostic prediction in patients with resectable gastric cancer. MATERIALS AND METHODS: One hundred and sixty-two patients with resectable gastric cancer were included …and separated into groups according to median pre-operative PLR or NLR values (PLR low: < 208 or PLR high: ≥ 208, and NLR low: < 4.02 or NLR high: ≥ 4.02, respectively). To evaluate the changes in PLR or NLR values after operation, we introduced the concept of postpre-operative PLR or NLR ratios (< 1 indicated PLR or NLR values were decreased after operation, while ≥ 1 suggested not decreased PLR or NLR values). RESULTS: Pre-operative PLR and NLR levels were significantly higher in gastric cancer patients compared with the healthy subjects. Low pre-operative PLR and NLR levels correlated with better clinicopathological features, including decreased depth of invasion, less lymph node metastasis and early tumor stage. Kaplan-Meier plots illustrated that higher pre-operative NLR and PLR had decreased overall survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted in a significant CONCLUSIONS: PLR and NLR measurements can provide important diagnostic and prognostic results in patients with resectable gastric cancer. Show more

Keywords: Gastric cancer, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR)

DOI: 10.3233/CBM-150534

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 899-907, 2015

Authors: Zhu, Hong | Peng, Yi-Gen | Ma, Shao-Gang | Liu, Hong

Article Type: Case Report

Abstract: BACKGROUND: The thyroperoxidase (TPO ) genetic variants in thyroid carcinoma is scarcely reported. OBJECTIVE: We report on a pedigree of thyroid papillary carcinoma and hypoechoic thyroid nodules with the TPO gene mutations. METHODS: The compound heterozygotic mutations of the TPO gene (c.2268-2269 insT and c.2090 G>A) in two patients with congenital goiters hypothyroidism were demonstrated. Fifteen family members of the proband and 105 control individuals were enrolled. The participants underwent clinical examination and molecular screening for TPO mutation. The hypoechoic thyroid nodules underwent fine needle aspiration biopsy. RESULTS: The …mutation c.2268-2269 insT was detected in the four family members with normal thyroid hormone levels. The other two members harbored the c.2090 G>A mutation. The heterozygotes had degeneratively hypoechoic thyroid nodules. The control individuals showed no mutation. The maternal grandfather developed a multifocal papillary thyroid carcinoma with lymph gland and nerve invasion in the left lobe of the thyroid gland. The maternal grandfather harbored the TPO c.2268-2269 insT mutation but without BRAF V600E mutation. Malignant cells were not observed in other members by fine needle aspiration biopsy. CONCLUSION: TPO genetic variants may be associated with thyroid carcinoma and hypoechoic thyroid nodules in a few cases. Long-term follow-up in the pedigree with congenital goiter is reasonable. Show more

Keywords: Papillary thyroid carcinoma, thyroperoxidase, mutation

DOI: 10.3233/CBM-150522

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 909-913, 2015

Article Type: Other

DOI: 10.3233/CBM-150556

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 915-920, 2015

Article Type: Other

Citation: Cancer Biomarkers, vol. 15, no. 6, pp. 921-931, 2015