Cancer Biomarkers - Volume 21, issue 3

Authors: Chai, Annie Wai Yeeng | Cheung, Arthur Kwok Leung | Dai, Wei | Ko, Josephine Mun Yee | Lee, Nikki Pui Yue | Chan, Kin Tak | Law, Simon Ying-Kit | Lung, Maria Li

Article Type: Research Article

Abstract: BACKGROUND: Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. OBJECTIVE: In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. METHODS: Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. RESULTS: The serum NID2 levels in ESCC patients (median 24.4 μ g/L) …are significantly higher (p = 4.3e-09) than that of the healthy controls (median 15.85 μ g/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μ g/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μ g/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175–3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μ g/L). CONCLUSIONS: In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients. Show more

Keywords: Nidogen-2, enzyme-linked immunosorbent assay, esophageal squamous cell carcinoma, serum biomarker, extracellular matrix protein

DOI: 10.3233/CBM-170484

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 583-590, 2018

Authors: Forcella, Matilde | Mozzi, Alessandra | Stefanini, Federico M. | Riva, Alice | Epistolio, Samantha | Molinari, Francesca | Merlo, Elisabetta | Monti, Eugenio | Fusi, Paola | Frattini, Milo

Article Type: Research Article

Abstract: BACKGROUND: Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression. OBJECTIVES: With the aim of improving the knowledge about sialidases deregulation in various cancer types, we investigated the amount of NEU1, NEU3 and NEU4 transcripts in paired normal and tumor tissues from 170 patients with 11 cancer types. METHODS: mRNA was extracted …from patients’ tissue specimens and retrotranscribed into cDNA, which was quantified by Real-Time PCR. RESULTS: We found NEU1 and NEU3 to be up regulated, while NEU4 was down regulated in most cancer types. In particular, colorectal cancer tissues showed the highest increase in NEU3 expression. Both NEU1 and NEU3 showed a strong up-regulation in ovarian cancer. CONCLUSIONS: Our data show that human sialidases are expressed at different levels in healthy tissues and are strongly deregulated in tumors. Moreover, sialidases expression in our European cohort showed significant differences from Asian populations. Some of these peculiar features open potential applications of sialidases in cancer diagnosis and therapy. Show more

Keywords: Sialome, sialidase expression, cancer progression, diagnosis and therapy

DOI: 10.3233/CBM-170548

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 591-601, 2018

Authors: Ricco, Gabriele | Cavallone, Daniela | Cosma, Chiara | Caviglia, Gian Paolo | Oliveri, Filippo | Biasiolo, Alessandra | Abate, Maria Lorena | Plebani, Mario | Smedile, Antonina | Bonino, Ferruccio | Pontisso, Patrizia | Brunetto, Maurizia Rossana

Article Type: Research Article

Abstract: BACKGROUND: The role of serum biomarkers in the surveillance of hepatocellular carcinoma (HCC) is controversial. OBJECTIVE: We assessed the diagnostic performances of alpha-fetoprotein (AFP) and protein-induced by vitamin-K-absence/antagonist-II (PIVKA-II) in 388 cirrhotic patients with chronic liver disease (CLD). METHODS: Biomarkers were quantified by automated chemiluminescent-enzyme-immunoassays (Fujirebio, Tokyo, Japan) at HCC diagnosis in 258 patients (204 males; median age 66.9 years) and in 130 cirrhotics without HCC (104 males; median-age 60.6 years). CLD etiology in HCC/non-HCC was CHB in 48/35, CHC in 126/56 and Non-Viral in 84/39. RESULTS: Overall AUROC values …for AFP and PIVKA-II were 0.698 (95%CI = 0.642–0.753, P < 0.001) and 0.780 (95%CI = 0.730–0.831, P < 0.001). AFP/PIVKA-II AUROC (95%CI) were: 0.822 (0.728–0.915)/0.833 (0.739–0.926) in CHB, 0.648 (0.560–0.736)/0.732 (0.650–0.814) in CHC; 0.640 (0.540–0.740)/0.806 (0.722–0.889) in Non-Viral-CLD. AFP/PIVKA-II diagnostic accuracy was 40.5–59.8%/62.7–73.5% and combining both markers 78.2% for CHB, 77% for Non-Viral-CLD and 75% for CHC. AFP correlated with ALT in HCC patients with CHC (ρ = 0.463/P < 0.001) and Non-Viral CLD (ρ = 0.359/P = 0.047), but not in CHB (treated with antivirals). PIVKA-II correlated with tumour size independently of CLD-etiology (P < 0.001) and AFP in CHB patients only (P = 0.007). CONCLUSION: The diagnostic performance of AFP and PIVKA-II is significantly influenced by the etiology and activity of CLD; their combination provides a better diagnostic accuracy. Show more

Keywords: Alpha-fetoprotein, protein induced by vitamin K absence/antagonist-II, HCC, chronic liver disease

DOI: 10.3233/CBM-170551

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 603-612, 2018

Authors: Zhao, Bin | Lu, Yu-Lin | Yang, Yong | Hu, Li-Bing | Bai, Yu | Li, Rui-Qian | Zhang, Guo-Ying | Li, Jun | Bi, Cheng-Wei | Yang, Li-Bo | Hu, Chen | Lei, Yong-Hong | Wang, Qi-Lin | Liu, Zhi-Min

Article Type: Research Article

Abstract: Long non-coding RNAs (lncRNAs) were playing critical roles in tumorigenesis. However, in prostate cancer, the roles and mechanisms of lncRNAs especially ANRIL were largely unknown. We investigated the effects of ANRIL on the proliferation and migration of prostate cancer cells using CCK-8 assay and Transwell migration assay. Real-time PCR and western blotting assays were used to analyze the levels of ANRIL, let-7a, TGF-β 1, p-Smad2 and p-Smad7. Our results showed that ANRIL was significantly overexpressed in prostate cancer tissues compared with corresponding normal tissues. Knockdown of ANRIL significantly inhibited the proliferation and migration of prostate cancer LNCap, PC3 …and DU145 cells. Knockdown of ANRIL significantly decreased the levels of TGF-β 1 and p-Smad2, and increased the level of p-Smad7 in prostate cancer LNCap cells. We further found that knockdown of ANRIL significantly enhanced the expression of let-7a, and rescue experiment found that let-7a inhibitor recovered the suppressive effects of ANRIL silencing on the proliferation and migration of prostate cancer LNCap, PC3 and DU145 cells. And let-7a inhibitor recovered the suppressive effects of ANRIL silencing on the activity of TGF-β 1/Smad signaling pathway in prostate cancer LNCap cells. Taken together, our findings indicated that overexpression of lncRNA ANRIL promoted the proliferation and migration of prostate cancer cells via regulating let-7a/TGF-β 1/Smad signaling pathway. Show more

Keywords: lncRNA ANRIL, prostate cancer, let-7a, TGF-β1/Smad signaling pathway

DOI: 10.3233/CBM-170683

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 613-620, 2018

Authors: Pirouzpanah, Saeed | Taleban, Forough-Azam | Mehdipour, Parvin | Sabour, Siamak | Atri, Morteza

Article Type: Research Article

Abstract: BACKGROUND: The option of endocrine therapy in breast cancer remains conventionally promising. OBJECTIVE : We aimed to investigate how accurately the pattern of hypermethylation at estrogen receptor (ESR ) and progesterone receptor (PgR ) genes may associate with relative expression and protein status of ER, PR and the combinative phenotype of ER/PR. METHODS : In this consecutive case-series, we enrolled 139 primary diagnosed breast cancer. Methylation specific PCR was used to assess the methylation status (individual test). Tumor mRNA expression levels were evaluated using real-time RT-PCR. Immunohistochemistry data was used to present hormonal receptor status …of a tumor (as test reference). RESULTS : Methylation at ESR1 was comparably frequent in ER-breast tumors (83.0%, P < 0.001; sensitivity = 83.0%, specificity = 65.2% and diagnostic odds ratio, DOR = 12.0) and strongly correlated with ER-/PR- conditions (Cramer’s V = 0.44, P < 0.001). Methylated PgRb promoter frequently was observed in tumors recognised as ER- or negative ER/PR (77.1%, P < 0.01). Assessment of DNA methylation of ESR1 harbouring methylation at PgRb was a case significantly suggested to be able to detect the lack of ER/PR expressions (55.6%, P < 0.01; sensitivity = 80.6%, specificity = 68.7% and DOR = 8.7). However, methylated PgRb was quite acceptable determinant to contribute with methylated ESR1 to rank tumors as ER-/PR- (64.4%, P < 0.01; sensitivity = 78.0%, specificity = 62.5% and DOR = 6.0). CONCLUSIONS : Despite the methylation status of ESR1 showed preponderant contribution to tumoral phenotypes of ER- and ER-/PR-, the hypermethylation of PgRb seem another epigenetic signalling variable actively associate with methylated ESR1 to show lack of ER+/PR+ tumors in breast cancer. Show more

Keywords: Breast cancer, hypermethylation, estrogen receptor, progestrone receptor

DOI: 10.3233/CBM-170697

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 621-638, 2018

Authors: Ma, Xingcong | Zhao, Xiaoyao | Yan, Wanjun | Yang, Jun | Zhao, Xixi | Zhang, Hong | Hui, Yuxin | Zhang, Shuqun

Article Type: Research Article

Abstract: BACKGROUND: Inhibition of lymphocytes infiltration and activity may impair antitumor immune response and limit treatment responsiveness. Wnt/β -catenin pathway has been suggested to contribute to immune evasion in tumor by suppressing the function of immune cells and excluding T cell infiltration. However, the effects of Wnt/β -catenin on TILs recruitment remain controversial. OBJECTIVE: We aimed to investigate whether intratumoral Wnt/β -catenin signaling could affect the lymphocyte infiltration in breast cancer. METHODS: The distribution of stromal TILs, CD8 + and FOXP3 + …TIL subsets, and the expression of β -catenin were separately assessed on consecutive sections of 96 breast cancer specimens. RESULTS: Both stromal infiltrated TILs and β -catenin expression were upregulated in hormone receptor negative HER2-enriched and TNBC subtypes. Furthermore, high levels of stromal TILs as well as CD8 + or FOXP3 + TIL subsets were associated with β -catenin overexpression by breast cancer, respectively. CONCLUSIONS: For the first time, we demonstrated that rather than excluding lymphocytes infiltration as reported in mela-noma, high levels of TILs were associated with β -catenin overexpression in BC. Wnt/β -catenin signaling may play a critical role in BC immunity, particularly in HER2-enriched and triple negative BC, and may serve as a potential target for regulating immune infiltrates in breast cancer. Show more

Keywords: Tumor infiltrating lymphocytes, Wnt/β-catenin signaling, CD8+ TILs, FOXP3+ TILs, breast cancer

DOI: 10.3233/CBM-170708

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 639-650, 2018

Authors: Zhang, Chun | Yang, Xi | Qi, Quan | Gao, Yuhai | Wei, Qiang | Han, Shuwen

Article Type: Research Article

Abstract: BACKGROUND: Chronic hepatitis C (CHC) is a contagious liver disease that results from infection with the hepatitis C virus (HCV). The most serious consequence of CHC is HCV-related hepatocellular carcinoma (HCC). OBJECTIVE: To illustrate the clinical significance of lncRNA HEIH expression in serum and exosomes in the development of HCV-related HCC. METHODS: Thirty-five CHC, twenty-two HCV-induced cirrhosis and ten HCV-related HCC patients in Huzhou Central Hospital from January 2016 to September 2016 were recruited in the present study. Basic patient information, clinical serological indicators, and clinical imaging data were investigated and analyzed. Serum …samples were collected from patients after receiving informed consent. Exosomes were extracted from the serum, and electron microscopy was used to observe the ultrastructure of exosomes. Quantitative PCR was used to detect lncRNA HEIH gene expression in serum and exosomes. RESULTS: The changes in the ALT, GGT, HDL, INR, Alb and AFP levels in the patients with HCV-induced cirrhosis and HCV-related HCC were statistically significant. In patients with HCV-related HCC, lncRNA-HEIH expression in serum and exosomes was increased, but the ratio of lncRNA-HEIH expression in serum versus exosomes was decreased compared to patients with CHC. Show more

Keywords: Chronic hepatitis C, cirrhosis, hepatocellular carcinoma, HEIH, exosome

DOI: 10.3233/CBM-170727

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 651-659, 2018

Authors: Chen, Yu-Hua | Zhou, Bi-Yun | Wu, Guo-Cai | Liao, De-Quan | Li, Jing | Liang, Si-Si | Wu, Xian-Jin | Xu, Jun-Fa | Chen, Yong-Hua | Di, Xiao-Qing | Lin, Qiong-Yan

Article Type: Retraction

Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.

Keywords: Exogenous interleukin-37, human lung adenocarcinoma A549 cells, biological characteristic, chemotaxis and regulatory T cells

DOI: 10.3233/CBM-170732

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 661-673, 2018

Authors: Fu, Shuang | Liu, Li | Zhang, Xin | Liu, Zhi-Ping | Wang, Rui-Tao

Article Type: Research Article

Abstract: BACKGROUND: Laryngeal cancer is one of the most common malignancies in the head and neck. Activated platelets play a critical role in cancer development and progression. Altered mean platelet volume (MPV) and platelet distribution width (PDW) have been found in various types of cancer. The purpose of the current study was to investigate the association of platelet indices with laryngeal cancer. STUDY DESIGN: The study included 216 patients with laryngeal cancer, 189 subjects with benign laryngeal disease, and 213 control subjects between January 2015 and December 2015. All participants’ clinical and laboratory characteristics at initial diagnosis …were collected. RESULT: MPV was significantly lower and PDW was markedly higher in laryngeal cancer patients compared with control subjects and patients with benign laryngeal disease. A significant correlation between MPV and lymph node metastasis was found. The prevalence of laryngeal cancer increased as MPV quartiles decreased and PDW quartiles increased. Furthermore, MPV and PDW were independent risk factors for distinguishing laryngeal cancer from benign laryngeal disease. CONCLUSIONS: The patients with laryngeal cancer have reduced MPV and increased PDW compared to the subjects without laryngeal cancer. In addition, MPV and PDW play different roles in laryngeal cancer from benign laryngeal disease. Show more

Keywords: Laryngeal cancer, mean platelet volume, platelet distribution width, diagnosis

DOI: 10.3233/CBM-170751

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 675-680, 2018

Authors: Wang, Pingan | Guo, Lingyu | Li, Kaipeng | Ning, Shanglei | Shi, Weichen | Liu, Zhaochen | Chen, Yuxin

Article Type: Research Article

Abstract: BACKGROUND: This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). METHODS: One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. RESULTS: …In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (P < 0.05). The expression of SRSF2 in HCC was not associated with gender (χ 2 = 0.014, P = 0.906), age (χ 2 = 0.007, P = 0.931), tumor size (χ 2 = 3.566, P = 0.059) and T stage (χ 2 = 2.708, P = 0.100), and was significantly correlated with tumor differentiation (χ 2 = 9.687, P = 0.007), lymph node metastasis (χ 2 = 4.827, P = 0.028), distal metastasis (χ 2 = 9.235, P = 0.002), tumor, node, metastasis (TNM) stage (χ 2 = 3.978, P = 0.046), portal vein invasion and serum alpha-fetoprotein (χ 2 = 14.919, P = 0.000). The expression of SRSF2 protein in hepatocellular carcinoma was positively correlated (r = 0.704, P < 0.05) with serum alpha-fetoprotein through Pearson analysis. The survival rates of SRSF2 overexpressing hepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). CONCLUSION: SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients. Show more

Keywords: SRSF2, hepatocellular carcinoma, immunohistochemistry, clinical pathology

DOI: 10.3233/CBM-170770

Citation: Cancer Biomarkers, vol. 21, no. 3, pp. 681-687, 2018