Cancer Biomarkers - Volume 18, issue 3

Authors: Zhang, Lan | Huang, Zebo | Zhang, Huo | Zhu, Mingxia | Zhu, Wei | Zhou, Xin | Liu, Ping

Article Type: Research Article

Abstract: BACKGROUND: Studies have reported the prognostic value of dysregulated microRNAs (miRNAs) in gastric cancer (GC). However, the results demonstrated so far are inconsistent. OBJECTIVE: To better understand the miRNAs with prognostic relevance. METHODS: Evaluable miRNAs were selected based on our selection criteria and further analyzed in formalin-fixed paraffin-embedded (FFPE) tissue samples of 169 GC patients using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 19 miRNAs were selected as candidate miRNAs. Among those miRNAs identified, high expression of miR-21-5p was related to poor overall survival (OS) and disease …free survival (DFS) and was identified as an independent prognostic factor. Cases with high level of miR-200c-3p showed poor DFS. Subgroup analysis revealed that high expression of miR-21-5p and miR-222-3p was associated with poor OS and DFS in GC patients not received adjuvant chemotherapy. In male patients, high expression level of miR-21-5p was related to poor OS and DFS. CONCLUSIONS: The present study confirmed that elevated level of miR-21-5p could serve as an independent predictor for poor OS and DFS of GC patients. Moreover, miR-200c-3p, miR-222-3p might also play important roles in the prognosis of GC patients. Further studies are warranted to validate our findings and identify the functions and mechanisms of these miRNAs. Show more

Keywords: MiRNA, gastric cancer, prognosis

DOI: 10.3233/CBM-160091

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 221-230, 2017

Authors: Huang, Kai | Chen, Jun | Yang, Mo-Song | Tang, Yu-Jun | Pan, Feng

Article Type: Research Article

Abstract: Chondrosarcomas are malignant cartilage-forming tumors from low-grade to high-grade aggressive tumors characterized by metastasis. Cisplatin is an effective DNA-damaging anti-tumor agent for the treatment against a wide variety of solid tumors. However, chondrosarcomas are notorious for their resistance to conventional chemo- and radio- therapies. In this study, we report miR-23b acts as a tumor suppressor in chondrosarcoma. The expressions of miR-23b are down-regulated in chondrosarcoma patient samples and cell lines compared with adjacent normal tissues and human primary chondrocytes. In addition, overexpression of miR-23b suppresses chondrosarcoma cell proliferation. By comparison of the cisplatin resistant chondrosarcoma cells and parental cells, we …observed miR-23b was significantly down regulated in cisplatin resistant cells. Moreover, we demonstrate here Src kinase is a direct target of miR-23b in chondrosarcoma cells. Overexpression of miR-23b suppresses Src-Akt pathway, leading to the sensitization of cisplatin resistant chondrosarcoma cells to cisplatin. This chemo-sensitivity effect by the miR-23b-mediated inhibition of Src-Akt pathway is verified with the restoration of Src kinase in miR-23b-overespressing chondrosarcoma cells, resulting in the acquirement of resistance to cisplatin. In summary, our study reveals a novel role of miR-23b in cisplatin resistance in chondrosarcoma and will contribute to the development of the microRNA-targeted anti-cancer therapeutics. Show more

Keywords: microRNA-23b, chondrosarcoma cells, cancer therapeutics, Src-Akt pathway

DOI: 10.3233/CBM-160102

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 231-239, 2017

Authors: Li, Guo-Jian | Chen, Qin-Yan | Harrison, Tim J. | Wang, Xue-Yan | Hu, Li-Ping | Yang, Qing-Li | Li, Kai-Wen | Fang, Zhong-Liao

Article Type: Research Article

Abstract: BACKGROUND: The accuracy of des-γ -carboxyprothrombin (DCP) in the detection of hepatocellular carcinoma (HCC) in those infected hepatitis B virus (HBV) from cross-sectional or case-control studies is contradictory. OBJECTIVE: To resolve this contradiction using a prospective study. METHODS: Three hundred male individuals persistently infected with HBV were recruited from the Chinese cohort and followed up once per year from 2012 to 2015. Each subject was screened for HCC by measurements of serum alpha-fetoprotein (AFP), lectin-bound α -fetoprotein (AFP-L3), DCP concentrations and ultrasonographic examinations. RESULTS: Nineteen HCC cases were identified. The …area under receiver operating characteristic (AUROC) at first, second and third visit for AFP, AFP-L3 and DCP ranges from 0.710-0.897, 0.566-0.637 and 0.520-0.595, respectively. The rate of elevated DCP is not significantly different between the HCC cases and controls (52.6% vs. 47.4%) (P > 0.05). The incidence of HCC in subjects with elevated DCP is not significantly higher than that of those with normal DCP (9.5% vs. 4.6%) (P > 0.05). The AUROC of combinations of these biomarkers was higher than that of AFP alone at the first visit. However, it was reduced at the second visit. At the third visit, the AUROCs of AFP + DCP and AFP + AFP-L3 + DCP, but not that of AFP + AFP-L3, were higher than that of AFP alone. CONCLUSIONS: AFP but DCP or AFP-L3 remains a valuable biomarker for HCC in those chronically infected with HBV. The combination with AFP-L3 and DCP may not increase the accuracy of AFP in differentiating HCC cases from controls, among those infected with HBV. Show more

Keywords: Hepatocellular carcinoma, hepatitis B virus, serum biomarker, the area under receiver operating characteristic

DOI: 10.3233/CBM-160131

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 241-248, 2017

Authors: Han, Jun | Meng, Qingyang | Xi, Qiulei | Wang, Haiyu | Wu, Guohao

Article Type: Research Article

Abstract: OBJECTIVE: Gastric cancer is one of the most common cancers worldwide, and the prognosis is still very poor due to the lack of specific and sensitive biomarkers. Aerobic glycolysis is one of the critical hallmarks of gastric cancer cells, and several glycolytic enzymes are highly expressed in gastric cancer patients. However, the expression and clinical significances of phosphofructokinase-2/fructose-2,6-bisphosphatase3 (PFKFB3, one of the glycolytic enzymes) in a large sample of gastric cancer patients remain unclear. METHODS: The expression of PFKFB3 was detected in 134 gastric cancer patients by qRT-PCR, immunohistochemistry, and western blot analyses. The correlation between …PFKFB3 expression and clinicopathological factors was analyzed by χ 2 test. In addition, we also analyzed whether the knockdown of PFKFB3 by siRNAs could inhibit the ability of gastric cancer cells (MGC-803 and AGS) to proliferate and migrate by MTT analysis and transwell analyses. RESULTS: PFKFB3 was highly expressed in 81.3% (109/134) of gastric cancer patients. The overexpression of PFKFB3 was associated with lymph node metastasis (P = 0.045) and TNM stage (P = 0.033). Knockdown of PFKFB3 by siRNAs significantly inhibited the proliferation and migration abilities of gastric cancer cells. CONCLUSION: Our data suggest that PFKFB3 might be a potential biomarker for gastric cancer and anti-neoplastic targeting gene. Show more

Keywords: Gastric cancer, PFKFB3, biomarker, cell proliferation, cell migration

DOI: 10.3233/CBM-160143

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 249-256, 2017

Authors: Shen, Xianjuan | Zhang, Yan | Wu, Xian | Guo, Yuehua | Shi, Wei | Qi, Jing | Cong, Hui | Wang, Xudong | Wu, Xinhua | Ju, Shaoqing

Article Type: Research Article

Abstract: OBJECTIVE: The purpose of this study was to explore serum PCAT-1 expression in multiple myeloma (MM) and examine the potential usefulness of this molecule as a biomarker for diagnosis in MM. METHODS: Serum samples were collected from 60 newly diagnosed untreated MM patients, and 48 healthy controls. Serum PCAT-1 expression levels were detected by RT-qPCR. In addition, correlations between the relative expression of serum PCAT-1 and the concentrations of lactic acid dehydrogenase (LDH), β2 M, λ light chain and κ light chain were assessed. RESULTS: It was found that the relative …expression of serum PCAT-1 in MM patients (81.02 ± 136.9) was higher than that in healthy controls (3.17 ± 5.75) (U= 307.0, P< 0.0001) and was significantly correlated with β2 M concentration (r= 0.461, P= 0.0002), but not with LDH, κ light and λ light chain concentration (r= 0.061, P= 0.641; r= 0.007, P= 0.956; r=-0.090, P= 0.499 respectively). Additionally, it was significantly correlated with different isotype of MM (H= 7.464, P= 0.024). The AUC of the ROC curve of serum PCAT-1 was 0.892 (95% CI 0.833-0.950), which was higher than other markers. Combining PCAT-1 and β2 M together, the sensitivity was highest compared with other markers alone, or combined. CONCLUSION: The expression levels of serum PCAT-1 in MM patients were significantly higher than that in healthy controls, suggesting that it may be useful in the auxiliary diagnosis of MM. Show more

Keywords: Multiple myeloma, PCAT-1, real-time quantitative PCR, auxiliary diagnosis

DOI: 10.3233/CBM-160158

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 257-263, 2017

Authors: Heydarov, Rustam | Titov, Sergei | Abramov, Mikhail | Timofeev, Edward | Mikhailovich, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Improving the efficacy of anticancer therapy remains an urgent and very important task. Screening of the individual genetic metabolism of cancer patients allows for prescribing adequate medication in the correct dose as well as for decreasing side effects associated with drug toxicity. OBJECTIVE: Estimation of a microarray-based method for genotyping of the UGT1A1 , DPYD , GSTP1 , and ABCB1 metabolic regulation genes to evaluate for an increased risk of toxicity of anticancer drugs. METHODS: The microarray was used to conduct genotyping of specimens taken from 115 cancer patients and 31 …healthy donors. RESULTS: A microarray-based method for identification of the rs8175347, rs3918290, rs1695, and rs1045642 polymorphisms in the corresponding UGT1A1 , DPYD , GSTP1 , and ABCB1 genes has been developed for genotyping. The results obtained were in full concordance with those obtained using control sequencing. The frequencies of the rs8175347, rs3918290, rs1695, and rs1045642 genetic variations were 0.38, 0, 0.35, and 0.56, respectively. CONCLUSION: The implementation of this biochip-based method in diagnostic practice should increase the overall survival and quality of life of cancer patients, decrease the length of their hospital stay, and reduce treatment costs. Show more

Keywords: Genotyping, polymorphisms, microarray, cancer, pharmacogenetics

DOI: 10.3233/CBM-160165

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 265-272, 2017

Authors: Luo, Dingyuan | Chen, Haibo | Lu, Penghui | Li, Xiaojuan | Long, Miaoyun | Peng, Xinzhi | Huang, Mingqing | Huang, Kai | Lin, Shaojian | Tan, Langping | Zhu, Yue | Chen, Zhibo | Ouyang, Nengtai | Li, Honghao

Article Type: Research Article

Abstract: OBJECTIVE: In this study, we examined the relationships between the expression level of CHI3L1 and the clinicopathological characteristics of papillary thyroid carcinoma. METHODS: A total of 322 tissue samples from patients with papillary thyroid carcinoma were collected, and the CHI3L1 expression levels in tumor tissues, matched adjacent noncancerous tissues were detected using immunohistochemistry (IHC) and qRT-PCR. The relationships between CHI3L1 expression levels and the clinical characteristics were evaluated. RESULTS: CHI3L1 expression was significantly increased in papillary thyroid carcinoma compared with matched adjacent noncancerous tissues (P< 0.001), tumor tissues with lymph node metastasis (LNM) …compared with tumor tissues without LNM (P< 0.001) and tumor tissues with distant organ metastasis (DOM) compared with tumor tissues without DOM (P< 0.01). CHI3L1 expression was significantly associated with tumor size (P= 0.0001), lymph node metastasis (P< 0.0001), distant organ metastasis (P< 0.0001), extrathyroid invasion (P= 0.0022), vascular invasion (P= 0.0004) and TNM stage (P= 0.0001). CHI3L1 overexpression in papillary thyroid carcinoma tissues correlates with the tumor malignant potential (P< 0.01). More importantly, Cox multifactor analysis indicated that patients with high CHI3L1 expression have lower overall survival, disease-free survival, lymph node recurrence-free survival, and distant recurrence free survival rates than those with low expression (P< 0.05). And our findings were further validated by online Oncomine database. CONCLUSIONS: CHI3L1 is associated with tumor metastasis and might be a prognostic biomarker for papillary thyroid carcinoma. Show more

Keywords: CHI3L1, immunohistochemistry, metastasis, prognosis, papillary thyroid carcinoma

DOI: 10.3233/CBM-160255

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 273-284, 2017

Authors: Luo, Ping | Jing, Wei | Zhu, Man | Li, Nan-Di | Zhou, Hu | Yu, Ming-Xia | Liang, Chun-Zi | Tu, Jian-Cheng

Article Type: Research Article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC), is an extremely aggressive malignancy with poor prognosis and high fatality rates worldwide. Accumulating evidence indicated that novel biomarkers are required to get a better understanding of the biological mechanisms of HCC. SRA1, a long non-coding RNA (lncRNA), serves as a critical regulator in several cancers. However, the association between SRA1 expression and tumorigenesis in HCC tissues remains unclear. OBJECTIVE: In the present study, we evaluated the expression of SRA1 in HCC and its clinical association. METHODS: The expression levels of SRA1 in 67 pairs of cancer tissues and …adjacent normal tissues from HCC patients were detected using quantitative real-time PCR. Expression of SRA1 in HCC cell lines compared with normal human hepatocyte cell lines was also measured. Finally, the potential associations between its level in HCC tissues and the clinicopathological parameters were analyzed as well. RESULTS: The results indicated that the expression levels of SRA1 in HCC were remarkably decreased, compared with matched normal tissues (P< 0.001). Levels of SRA1 in HCC cell lines were also significantly decreased than that in normal human hepatocyte cell line L-02. Additionally, the levels of SRA1 were significantly associated with tumor size (P= 0.020) and serum GLU level (P= 0.046). CONCLUSIONS: This study highlighted that SRA1 was downregulated in HCC and might serve as a tumor suppressor in HCC, which laid a solid foundation for future research. Show more

Keywords: Long non-coding RNA, SRA1, HCC, down-expression

DOI: 10.3233/CBM-160305

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 285-290, 2017

Authors: Cherdyntseva, Nadezda | Gervas, Polina | Voropaeva, Elena | Denisov, Evgeny | Pisareva, Lubov | Malinovskaya, Elena | Maksimov, Vladimir | Voevoda, Michail | Perinov, Dmitriy | Panferova, Yelena | Cherdyntsev, Evgeny | Choynzonov, Evgeny

Article Type: Research Article

Abstract: BACKGROUND: The BRCA1 mutations that are endemic to the Slavic population of Russia have not been identified among indigenous peoples, including the Buryats, Tuvinians and Altaians with hereditary breast cancer. OBJECTIVE: This study was aimed to identify the mutations that are responsible for the occurrence of hereditary breast cancer in the indigenous population of the Republic of Buryatia. METHODS: Mutations in the BRCA1 gene were identified in blood samples by Sanger-based sequencing. RESULTS: We identified 11 polymorphisms (10 SNPs and 1 Indel) and 6 new unclassified sequence variants in …the BRCA1 gene. In our study three new sequence variants (c.321T>A, c.366T>A, c.4357+2T>A) were found in position of previously described polymorphisms in dbSNPs: rs80357544 (c.321delT), rs190900046 (c.366T>G), and rs80358152 (c.4357+2T>C), respectively. Other three new sequence variants (c.3605A>G, c.1998A>C, and c.80+13A>C) have not been previously described in dbSNP, BIC and Human Gene Mutation Databases. CONCLUSIONS: We described six new sequence variants that have never been published in the literature or databases. Further studies are required to confirm the impact of new sequence variants on the risk of breast cancer in the Buryat Mongol population. Show more

Keywords: BRCA1, mutation, breast cancer, Buryat, Mongoloid race

DOI: 10.3233/CBM-161649

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 291-296, 2017

Authors: Ma, Kewei | Xu, Wang | Wang, Chang | Li, Biao | Su, Keju | Li, Wei

Article Type: Research Article

Abstract: OBJECTIVES: This study aimed to examine the prognostic role of the plasma 25-hydroxyvitamin D (25(OH)D) level in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based doublet first-line chemotherapy. METHODS: A total of 195 advanced NSCLC patients were consecutively and prospectively hospitalized to receive platinum-based first-line chemotherapy. The baseline 25(OH)D level was measured at the time of diagnosis. Main outcome measures included overall survival (OS) and progression-free survival (PFS). RESULTS: With 10 ng/mL as the cutoff value for the baseline plasma 25(OH)D level, patients with 25(OH)D < 10 ng/mL (n = 54) …and those with 25(OH)D ≥ 10 ng/mL (n = 141) were found to have similar characteristics in terms of age, sex, smoking status, pathological type, Eastern Cooperative Oncology Group (ECOG) performance status, and clinical staging (all P-values > 0.05). The median OS values of patients with 25(OH)D < 10 ng/mL and ≥ 10 ng/mL were 17.9 months (95% confidence interval [CI], 14.4-21.4 months) and 20.8 months (95%CI, 17.9-23.8 months), respectively; the median PFS values were 9.4 months (95%CI, 8.2-10.5 months) and 9.4 months (95%CI, 8.3-10.5 months), respectively. Both univariate and multivariate analyses showed that having a plasma 25(OH)D level < 10 ng/mL was associated with a significantly shorter OS (P = 0.003; P = 0.009), while the baseline plasma 25(OH)D level was not significantly associated with PFS. CONCLUSION: Deficiency of 25(OH)D is an independent prognostic factor for a poor OS in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Show more

Keywords: Non-small cell lung cancer, advanced, platinum-based first-line chemotherapy, 25(OH)D, survival, prognostic factor

DOI: 10.3233/CBM-161687

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 297-303, 2017

Authors: Zhai, Ling-Ling | Zhou, Jiao | Zhang, Jing | Tang, Xi | Zhou, Ling-Yu | Yin, Jia-Yu | Vanessa, Minse-Evola Deniz | Peng, Wen | Lin, Jiang | Deng, Zhao-Qun

Article Type: Research Article

Abstract: OBJECTIVES: This study was intended to investigate the expression status of Vimentin 2p (VIM 2p) , a pseudogene of Vimentin , and further analyze its clinical significance in AML patients. METHODS: Real-time quantitative PCR (RQ-PCR) was employed to explore the expression status of VIM 2p in 128 patients with de novo AML and 36 healthy controls. RESULTS: The expression level of VIM 2p was significantly decreased compared with healthy controls (P< 0.001). The patients with low VIM 2p expression were identified in 93 of 128 (73%) of AML patients. …No significant differences could be observed in sex, age, blood parameters, FAB/WHO subtypes, karyotype risks and ten gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3 A, C/EBPA, N/K-RAS and U2AF1 ) between VIM 2p low-expressed and high-expressed patients (P> 0.05). Patients with low VIM 2p expression had significantly shorter overall survival (OS) than those with high VIM 2p expression in whole AML cases (median 7 vs. 13 months, respectively, P= 0.032), besides cytogenetically normal AML (CN-AML) and non-M3 AML cohort (P= 0.042 and 0.045, respectively). CONCLUSIONS: These findings indicate that VIM 2p down-regulation is a common event in AML and may be associated with poor clinical outcome. Show more

Keywords: Pseudogene, Vimentin 2p, prognostic marker, acute myeloid leukemia

DOI: 10.3233/CBM-160247

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 305-312, 2017

Authors: Carvalho, Ivna N.S.R. | Reis, Adriana H.O. | dos Santos, Anna C.E. | Vargas, Fernando R.

Article Type: Research Article

Abstract: BACKGROUND: Retinoblastoma (RB) is a malignant pediatric tumor and, mainly because of late diagnosis, most patients undergo enucleation. The tumor almost always initiates by two inactivation events at the RB1 gene. Single nucleotide polymorphisms (SNPs) in p53 pathway have been found to represent genetic modifiers of RB. OBJECTIVE: To investigate whether a SNP (rs4938723T > C) in mir-34b/c gene, a key effector of p53, could influence RB risk and patients' age of onset. METHODS: mir-34b/c rs4938723T > C was sequenced in 130 RB patients and in 105 control individuals. Statistical analysis consisted …of χ 2 tests or Fisher's exact, odds ratios (ORs) and Mann-Whitney test. RESULTS: The presence of the C allele did not change the risk for retinoblastoma. However, in hereditary RB patients, the mean age at diagnosis is much lower (1.4 ± 1.4 months) among CC carriers than when it is compared to TT genotype (13.8 ± 6.4, p = 0.001). Besides, hereditary RB patients with CC genotype are around 4 times more likely to present retinoblastoma under the age of 3 months (OR = 4.44; IC: 2.50-7.90; p = 0.002). CONCLUSIONS: The C allele together with a germ-line RB1 gene mutation may speed retinoblastoma onset which suggests that mir-34b/c rs4938723T > C may represent a candidate biomarker for hereditary RB. Show more

Keywords: Retinoblastoma, mir-34b/c, rs4938723, age at diagnosis

DOI: 10.3233/CBM-160248

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 313-317, 2017

Authors: Yu, Yalan | Zuo, Jiangcheng | Tan, Qian | Zar Thin, Khaing | Li, Ping | Zhu, Man | Yu, Mingxia | Fu, Zhenming | Liang, Chunzi | Tu, Jiancheng

Article Type: Research Article

Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in the carcinogenesis and progression of cancers. Aberrant expression of miRNAs in tissue and plasma has been found in various solid tumors. Our research aims to determine whether the abnormal plasma miRNA expression patterns can be used as a predictive marker for the diagnosis and prognosis of small cell lung cancer (SCLC). Fifty SCLC patients and 30 healthy controls annotated with clinical characteristics and specific questionnaire survey for smoking history were available. Quantification of several miRNAs (miR-20a-5p , miR-92a-2-5p and miR-17-5p ) was performed using quantitative real-time polymerase chain …reaction (qRT-PCR), and results were analyzed using SPSS statistics 17.0. Plasma miR-92a-2 level was significantly higher in the SCLC patients group compared with healthy control (P< 0.0001), the receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were at 100% and 56% for diagnosis of SCLC, area under the ROC curve (AUC) was 0.761. No other statistically significant differences were found in the expression level of plasma miR-92a-2 among survival analysis in SCLC. Detection of miR-92a-2 levels in plasma could be a potential and noninvasive method for the diagnosis of SCLC. Show more

Keywords: MiR-92a-2, plasma, small cell lung cancer, diagnosis

DOI: 10.3233/CBM-160254

Citation: Cancer Biomarkers, vol. 18, no. 3, pp. 319-327, 2017