Cancer Biomarkers - Volume 21, issue 2

Authors: Benlahfid, Mohammed | Traboulsi, Wael | Sergent, Frederic | Benharouga, Mohamed | Elhattabi, Khalid | Erguibi, Driss | Karkouri, Mehdi | Elattar, Hicham | Fadil, Abdelaziz | Fahmi, Yassine | Aboussaouira, Touria | Alfaidy, Nadia

Article Type: Research Article

Abstract: BACKGROUND: The highest risk factor for mortality among malignant tumors is metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor which biological activity is mediated via two G protein-coupled receptors, prokineticin receptor1 (PROKR1) and PROKR2. Recent studies suggested that EG-VEGF expression is deregulated in multiple cancers including colorectal cancer (CRC). METHODS: Using distinctive CRC and peritoneal carcinomatosis (PC) cohorts and a corresponding control cohort, we determined the circulating levels of EG-VEGF and its in situ expression, and that of its related receptors. RESULTS: Circulating EG-VEGF levels were significantly increased …in patients with metastatic PC compared to CRC and control patients (p < 0.05). Furthermore, according to clinicopathologic examinations, local EG-VEGF expression correlated with higher tumor and nodal stages (p < 0.001) of CRC. EG-VEGF and PROKR2 were highly expressed in colorectal primary lesions compared to positive controls. PROKR1 expression was lower and did not change in tumor specimens. Also, EG-VEGF and its receptor PROKR2 were differentially expressed in the colorectal primary lesions and in the control groups. CONCLUSION: Altogether these findings suggest that EG-VEGF/receptors system might be an important actor in the CRC progression into PC and might be involved in the ability of tumor cells to invade other organs. Circulating EG-VEGF could be proposed as a prognostic marker in human CRC and its progression into PC. Show more

Keywords: Prokineticin, colorectal cancer, peritoneal carcinomatosis, EG-VEGF

DOI: 10.3233/CBM-170499

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 345-354, 2018

Authors: Wu, Dong-Ming | Shi, Jiao | Liu, Teng | Deng, Shi-Hua | Han, Rong | Xu, Ying

Article Type: Research Article

Abstract: Cervical cancer is the fourth most common malignancy among women worldwide, and continued research to discover biomarkers or therapeutic targets will aid early diagnosis and treatment of this cancer. Here, we investigated novel cervical cancer biomarkers using integrated analysis of high-throughput sequencing data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We have identified nine genes of interest that appear to be involved in cervical cancer development: SPARCL1 , SYCP2 , KIF4A , PRC1 , TOP2A , LAMP3 , KIF20A , MCM2 , and APOBEC3B . Furthermore, gene ontology (GO) and co-expression analysis of these …differentially expressed genes indicated that SPARCL1 may play a core role in cervical cancer development. Further, we analyzed the expression of these nine genes during the progression of cervical cancer, and found that SPARCL1 is also related to precancerous lesions and migration processes during cervical cancer pathogenesis. Finally, we validated these observations by investigating SPARCL1 expression in cervical cancer tissue and serum samples. The diagnostic specificity of serum SPARCL1 in cervical cancer occurrence was also compared with other high incidence diseases. All of these data indicate that SPARCL1 may be a novel cancer predictive marker and a potential therapeutic target for tumor development and progression in cervical cancer. Show more

Keywords: Cervical cancer, SPARCL1, marker

DOI: 10.3233/CBM-170501

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 355-365, 2018

Authors: Wang, Dong | Ji, Zhi-Gang | Li, Han-Zhong | Zhang, Yu-Shi

Article Type: Research Article

Abstract: OBJECTIVE: To assess whether adrenalectomy may improve biochemical and metabolic impairment for patients with subclinical Cushing syndrome (SCS) due to adrenal incidentaloma (AI) compared with conservative management. METHODS: A total of 87 patients with SCS due to AI in Peking Union Medical College Hospital between September 2011 and January 2016 have been treated. Forty-eight patients underwent laparoscopic adrenalectomy (operative group), whereas 39 were managed conservatively (control group). RESULTS: The duration of follow-up was 32.5 ± 10.6 months in operative group, and 30.1 ± 13.1 months in control group, respectively. In …the operative group, laboratory corticosteroid parameters normalized in all patients but not in the control group. In the operative group, BP of hypertensive patients improved or normalized (22 of 48); to the contrary, in the control group, cure or improvement was never achieved among the patients with hypertension, whereas a worsening was observed in 5 patients (P = 0.004). No significant difference was found in glycemic control and blood lipid change between the two groups. However, a decrease in triglyceridaemia and HBA1c was found in operative group compared with the control group (P = 0.011 and P = 0.017, respectively). Substitutive corticosteroid treatment was administered in 3 patients due to postoperative adrenal insufficiency during hospital stay, and the duration of treatment was 9 weeks, 10 weeks and 12 weeks, respectively. CONCLUSIONS: Laparoscopic adrenalectomy should be performed for patients with SCS due to AI. Show more

Keywords: Subclinical Cushing’s syndrome, adrenal incidentaloma, adrenalectomy

DOI: 10.3233/CBM-170531

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 367-372, 2018

Authors: Fang, Enhao | Zhang, Xiuqing

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer (BC) is the second most common cause of death from cancer in women in the United States. As the molecular mechanism of BC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing molecular mechanism of breast cancer initiation and progression. OBJECTIVE: This study aimed to identify potential biomarkers and survival analysis of hub genes for BC treatment. METHODS: The differentially expressed genes (DEGs) between breast cancer and normal cells were screened using microarray data obtained from the Gene Expression Omnibus (GEO) database. …Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS) analysis of hub genes was performed by the Kaplan-Meier plotter online tool. Finally, the potential molecular agents were identified with Connectivity Map (cMap) database. RESULTS: A total of 585 DEGs were obtained, which were significantly enriched in the terms related to positive regulation of cell migration, regulation of cell proliferation and focal adhesion. KEGG pathway analysis showed that the significant pathways included Focal adhesion, Pathways in cancer, ECM-receptor interaction, Ribosome, Transcriptional misregulation in cancer and other signaling pathways about cancer. The PPI network was established with 576 nodes and 1943 edges. A significant module was found from the PPI network, the enriched functions and pathways included ECM-receptor interaction and Focal adhesion. CONCLUSIONS: Fifteen genes were selected as hub genes because of high degrees, among which, low expression of four genes was associated with worse OS of patients with BC, including RPS9 , RPL11 , RPS14 and RPL10A . Additionally, the small molecular agent emetine may be a potential drug for BC. Show more

Keywords: Breast cancer, bioinformatics analysis, differently expressed genes, hub genes, therapeutic agent, survival analysis

DOI: 10.3233/CBM-170550

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 373-381, 2018

Authors: Zuo, Jiangcheng | Yu, Yalan | Zhu, Man | Jing, Wei | Yu, Mingxia | Chai, Hongyan | Liang, Chunzi | Tu, Jiancheng

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS: The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore …whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS: In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS: Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer. Show more

Keywords: miR-155, breast cancer, cancer stem cell, MDA-MB-231, Doxorubicinol

DOI: 10.3233/CBM-170642

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 383-392, 2018

Authors: Hussain, Lal | Ahmed, Adeel | Saeed, Sharjil | Rathore, Saima | Awan, Imtiaz Ahmed | Shah, Saeed Arif | Majid, Abdul | Idris, Adnan | Awan, Anees Ahmed

Article Type: Research Article

Abstract: Prostate is a second leading causes of cancer deaths among men. Early detection of cancer can effectively reduce the rate of mortality caused by Prostate cancer. Due to high and multiresolution of MRIs from prostate cancer require a proper diagnostic systems and tools. In the past researchers developed Computer aided diagnosis (CAD) systems that help the radiologist to detect the abnormalities. In this research paper, we have employed novel Machine learning techniques such as Bayesian approach, Support vector machine (SVM) kernels: polynomial, radial base function (RBF) and Gaussian and Decision Tree for detecting prostate cancer. Moreover, different features extracting strategies …are proposed to improve the detection performance. The features extracting strategies are based on texture, morphological, scale invariant feature transform (SIFT), and elliptic Fourier descriptors (EFDs) features. The performance was evaluated based on single as well as combination of features using Machine Learning Classification techniques. The Cross validation (Jack-knife k-fold) was performed and performance was evaluated in term of receiver operating curve (ROC) and specificity, sensitivity, Positive predictive value (PPV), negative predictive value (NPV), false positive rate (FPR). Based on single features extracting strategies, SVM Gaussian Kernel gives the highest accuracy of 98.34% with AUC of 0.999. While, using combination of features extracting strategies, SVM Gaussian kernel with texture + morphological, and EFDs + morphological features give the highest accuracy of 99.71% and AUC of 1.00. Show more

Keywords: Prostate cancer, support vector machine (SVM), decision tree, Bayesian approach, morphological, scale invariant feature transform (SIFT), texture, and elliptic fourier descriptors (EFDs)

DOI: 10.3233/CBM-170643

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 393-413, 2018

Authors: Ruan, Libo | Chen, Jun | Ruan, Litao | Yang, Tianrui | Wang, Ping

Article Type: Research Article

Abstract: MicroRNAs are a class of small non-coding RNA molecules that play crucial roles in the initiation and progression of lung cancer. This study was undertaken to investigate the expression and roles of miR-186 in lung cancer. Ectopic expression experiments demonstrated that miR-186 functions as a tumor suppressor. Bioinformatic predictions, a luciferase reporter assay, and protein expression analysis suggested that miR-186 could inhibit the protein levels of SIRT6, a purported tumor suppressor gene. Collectively, our results indicated that miR-186 could inhibit lung cancer progression through targeting SIRT6 and that miR-186 may be a therapeutic target for lung cancer.

Keywords: Lung cancer, microRNA, miR-186, SIRT6, apoptosis

DOI: 10.3233/CBM-170650

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 415-423, 2018

Authors: Zuo, Li | Ying, Jiang-Shan | Zhang, Feng-Chun | Xu, Ying-Chun

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the correlation of katanin P60 expression with clinicopathological grade and overall survival (OS) in patients with breast cancer (BC). METHODS: Three hundred and four operative BC patients were retrospectively reviewed in this cohort study. Tumor tissue sample was acquired from each patient during surgery. Immunofluorescent staining was used to assess katanin P60 expression. RESULTS: There were 265 BC patients with katanin P60 negative expression and 75 patients with katanin P60 positive expression. Higher N stage (p < 0.001) and TNM stage (p < …0.001) were observed in katanin P60 positive expression group compared to katanin P60 negative expression group. Kaplan-Meier (K-M) curves showed association of katanin P60 positive expression status with shorter OS. Multivariate Cox analysis illustrated katanin P60 positive expression (p < 0.001) could independently predict worse OS. Subgroups analysis indicated that katanin P60 positive expression correlated with worse OS in patients of TNM stage II (p = 0.001) and stage III (p =0.001), while no correlation was found between katanin P60 expression and OS in BC patients with stage I (p = 0.538). According to molecular subtypes, katanin P60 positive expression was correlated with shorter OS in patients with HER2 + HR + (p < 0.001), HER2 + HR - (p < 0.001) and HER2 - HR - (p = 0.001) status compared to katanin P60 negative expression, while no correlation between katanin P60 expression and OS was observed in patients with HER2 - HR + (p = 0.073). CONCLUSION: Katanin P60 positive expression was correlated with higher lymph node metastasis and worse OS, and it could be regarded as a novel and convincing biomarker to independently predict the prognosis of BC patients. Show more

Keywords: Tumor tissue, katanin P60, breast cancer, prognosis

DOI: 10.3233/CBM-170666

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 425-432, 2018

Authors: Rodríguez-Molinero, Alejandro | Hercbergs, Aleck | Sarrias, Manuel | Yuste, Antonio

Article Type: Research Article

Abstract: Preclinical studies have attributed 3,3’,5-triiodo-L-thyronine (T3) a direct negative effect on tumor progression, as well as chemosensitizing, differentiating and immunomodulatory properties. On the other hand, L-thyroxine (T4), via a thyroid hormone receptor on plasma membrane integrin α vβ 3, promotes solid tumor growth and neoangiogenesis, therefore lowering endogenous T4 reduces tumor growth rate. We present the case of two patients with metastatic triple negative breast cancer and metastatic pancreatic cancer respectively, who benefit of the sole treatment with antithyroid drugs and exogenous administration of T3 (liothyronine). In these cases tumor growth was accompanied by T3 depletion …in plasma, which may represent a novel marker for progression. Show more

Keywords: Neoplasm metastasis, pancreatic neoplasms, thyroid hormones, triiodothyronine, triple negative breast neoplasms

DOI: 10.3233/CBM-170668

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 433-438, 2018

Authors: Wang, Yang-Kun | Wang, Su-Nan | Li, Ying-Ying | Wang, Gong-Ping | Yun, Tian | Zhu, Chao-Ya | Yang, Bin-Feng | Li, Cong-Yang | Jiang, Bo | Zhu, Mei-Ling

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma. RESULTS: The expression rate of HER2 protein was 39.3% (53/135). Among these positive cases, patients with HER2 protein (3+) accounted for 9.6% (13/135), patients with HER2 protein (2+) accounted for …13.3% (18/135), and patients with HER2 protein (1+) accounted for 16.3% (22/135). The amplification rate of the HER2 gene was 35.8% (19/53). In the detection of the mRNA expression of ERCC1, TUBB3 and TYMS, 45 patients had low and moderate single gene expression, 50 patients had low and moderate double gene expression, 22 patients had low and moderate mRNA expression for ERCC1, TUBB3 and TYMS, and 18 patients had no low and moderate expression. Among the 53 patients with HER2 protein expression and 22 patients with low and moderate mRNA expression of ERCC1, TUBB3 and TYMS, 12 patients received chemotherapy and trastuzumab. Follow-up results revealed that HER2 gene status was positively correlated with the therapeutic effect of the combined treatment in patients with low mRNA expression of ERCC1, TUBB3 and TYMS. Among these patients, five patients with extensive HER2 (3+), HER2 cluster-specific amplification, and low mRNA expression of ERCC1, TUBB3 and TYMS had a total survival of up to 19.1 months. CONCLUSIONS: The detection of HER2 in gastric cancer is highly heterogeneity, and the combined detection of HER2 protein expression, HER2 gene amplification and chemosensitivity can provide important reference markers for the benefit of antitumor drugs. Show more

Keywords: Stomach neoplasms, HER2 gene, HER2 protein, FISH, IHC, fluorescence RT-PCR

DOI: 10.3233/CBM-170671

Citation: Cancer Biomarkers, vol. 21, no. 2, pp. 439-447, 2018