Cancer Biomarkers - Volume 21, issue 4

Authors: Yang, Jian-Gong | He, Xiao-Feng | Huang, Bing | Zhang, Hui-Ai | He, Yong-Kang

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to explore the rule of changes in serum GGT activity, as well as GGT/ALT and AST/ALT ratios, in primary hepatic carcinoma (PHC) patients with different alpha-fetal protein (AFP) levels. METHODS: GGT, AST and ALT were detected in 370 PHC patients with positive HBs-Ag using a automatic biochemical analyzer, and AFP was detected using a Roche E170 modular analytics immunoassay analyzer. GGT level, as well as AST/ALT and GGT/ALT, ratios were compared among PHC patients with different AFP levels. RESULTS: As shown in Table 1 , GGT levels were 109.59 ± …111.06, 151.13 ± 190.43, 135.86 ± 107.62, 151.36 ± 176.59 and 172.58 ± 188.84, respectively, in the groups of primary PHC patients with AFP levels of ⩽ 10, 10–100, 100–200, 200–400 and ⩾ 400 ng/ml; and the differences among these groups were not statistically significant (P > 0.05). AST/ALT ratios were 1.55 ± 1.02, 1.30 ± 0.81, 2.02 ± 1.89, 2.12 ± 1.11 and 1.73 ± 1.25, respectively; and the differences among these groups were not statistically significant (P > 0.05). GGT/ALT ratios were 3.43 ± 3.12, 3.57 ± 5.70, 3.57 ± 2.94, 3.89 ± 4.58 and 3.43 ± 3.61, respectively; and the differences among these groups were not statistically significant (P > 0.05). CONCLUSION: For patients with chronic hepatitis B and cirrhosis after hepatitis B, no matter how AFP level is, when liver function report reveals increased GGT, AST/ALT > 1 and GGT/ALT > 1 (that is, AST > ALT and GGT > ALT), even if AFP is negative, we should also be alert to the existence of PHC. Show more

Keywords: Liver neoplasms, hepatitis B, liver cirrhosis, GGT

DOI: 10.3233/CBM-170088

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 743-746, 2018

Authors: Neumann, Mirko Peter | González, María Victoria | Pitiot, Ana S. | Santamaría, Íñigo | Martínez, Cristina | Tardón, Adonina | Astudillo, Aurora | Balbín, Milagros

Article Type: Research Article

Abstract: BACKGROUND: Lung cancer is a leading cause of death worldwide, with poor survival rates despite diagnostic and therapeutic advances. Markers are needed in order to improve clinical patient management and survival. TP53 is frequently involved in lung cancer development with polymorphic sites potentially having a role in it. This study aims to determine the value of codon 72 missense polymorphic variant genotyping, TP53 R72P, as a prognostic factor in NSCLC patients. METHODS: One hundred and fifteen NSCLC samples from patients exposed to tobacco smoke and silica dust from Asturias (Northern Spain) were genotyped by …direct sequencing. RESULTS: Seventy-five percent tumour samples alleles coded for Arg. The R72P genotype was an independent predictor of lymph node status (HR = 3.6). The heterozygous genotype was associated to a reduced 5-year survival rate (28% vs 51% for homozygotes). Importantly, this result was specifically observed in these subsets of patients: those over 67 years, patients with silicosis, current smokers, patients with squamous cell carcinomas and, notably, with tumour free lymph nodes. CONCLUSION: Our results indicate a remarkable application of R72P genotyping in the clinical setting: refine patient subclassification to identify those with an adverse clinical course despite tumour free lymph node status. Show more

Keywords: NSCLC, TP53, R72P, polymorphism, prognosis

DOI: 10.3233/CBM-170230

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 747-754, 2018

Authors: Zhang, Qing-An | Yang, Xu-Hai | Chen, Dong | Yan, Xiang | Jing, Fu-Chun | Liu, Hong-Qian | Zhang, Ronghua

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTION”. The retraction notice is available at http://doi.org/10.3233/CBM219903

Keywords: Pancreatic cancer, chemoresistance, miR-34, Slug, PUMA

DOI: 10.3233/CBM-170289

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 755-762, 2018

Authors: Zhang, Jiajia | Wang, Tong | Zhang, Yong | Wang, Hao | Wu, Yubing | Liu, Kunhe | Pei, Chong

Article Type: Research Article

Abstract: OBJECTIVE: Emerging studies show that microRNAs (miRNAs) play a essential role in tumorigenesis. Deregulation of miR-494 is frequently observed in various human cancers including non-small cell lung cancer (NSCLC). However, little is known about the clinical significance of serum miR-494. The aim of this study was to investigate the diagnostic and prognostic value of serum miR-494 for NSCLC. METHODS: We first compared miR-494 levels between NSCLC cell lines and lung bronchus epithelial cell line. A total of 90 NSCLC patients and 50 healthy controls were included in this study. MiR-494 levels were examined in serum samples …by using real-time quantitative reverse transcription polymerase chain reactions. Association between serum miR-494 levels and the prognosis of NSCLC was further analyzed. RESULTS: Our results showed that miR-494 was elevated in NSCLC cell lines. Serum miR-494 levels were significantly increased in patients with NSCLC compared to healthy controls. Area under receiver operating characteristic (ROC) curve was 85.4%. In addition, serum miR-494 levels decreased remarkably when patients received effective therapy. High serummiR-494 levels were significantly associated with higher incidence of lymph node metastasis, advanced clinical stage and higher histological grade. Moreover, survival analysis demonstrated that patients in the high serum miR-494 group had a poorer 5 year overall survival and disease free survival compared with the patients in the low serum miR-494 group. Multivariate analysis showed that serum miR-494 was an independent risk factor. CONCLUSIONS: In conclusion, serum miR-494 was significantly elevated in NSCLC patients and closely correlated with poor clinical outcome, indicating that serum miR-494 might be a useful diagnostic and prognostic marker for NSCLC. Show more

Keywords: Biomarker, diagnosis, non-small cell lung cancer, serum miR-494, prognosis

DOI: 10.3233/CBM-170337

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 763-768, 2018

Authors: Cui, Jian | Wang, Qian | Wang, Hai-Bo | Wang, Bin | Li, Ling

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Breast cancer is the leading cause of death in women worldwide. There are evidences that human cytomegalovirus (HCMV) infection is associated with several malignant tumors. This study aims to investigate the infection of human cytomegalovirus (HCMV) in a large sample of breast cancer patients, and conduct a correlation analysis of clinical and pathological factors, to provide evidence for whether HCMV infection is associated with breast cancer development, progression and metastasis. MATERIALS AND METHODS: A total of 438 tissue samples (including breast cancer tissue, paracancerous tissue and sentinel lymph node [SLN] tissue) obtained from 146 …patients who were diagnosed with breast cancer and intraoperatively underwent unilateral axillary SLN biopsy at the Affiliated Hospital of Qingdao University from June 2013 to June 2014 were included into this study. These tissue samples were divided into two groups: SLN positive group and SLN negative group. The clinical information is collated and numbered. Normal breast tissues of 40 patients with cyclomastopathy were taken as controls. The expressions of HCMV immediate-early (IE) and late antigen (LA) proteins of breast cancer tissues, paracancerous tissues, SLN tissues and normal breast tissues were analyzed by immunohistochemistry, and HCMV infection of the samples was graded according to the percentage of the positive cells, and HCMV IE2 mRNA expression was detected by reverse transcription polymerase chain reaction. The clinical data were collated and statistically analyzed. RESULTS: HCMV IE and LA proteins were highly expressed in all breast cancer tissue samples. IE proteins were detected in 47.9% (70/146) of paracancerous tissue samples, and LA proteins were detected in 53.4% (78/146) of paracancerous tissue samples. IE and LA proteins were expressed in 92.6% of metastatic SLN samples (62/68) and in most of the tumor cells. Inflammatory cells in 60% (42/70) of non-metastatic samples were positive for HCMV. HCMV DNA was present in 100% of breast cancer tissue samples, 50% of paracancerous tissue samples, and 91% of metastatic SLN samples; but this was not present in HCMV negative and non-metastatic SLN samples. Differences in HCMV infection, and estrogen receptor-α , progesterone receptor, Elston classification, Ki67 percentage, Her-2 and Luminal type and other clinical indicators were not statistically significant. CONCLUSION: HCMV infection is common in breast cancer tissues, paracancerous tissues and SLN tissues. The severity of HCMV infection varied markedly with tissue type. HCMV infection might be associated with metastasis and invasion of breast cancer. The expression of HCMV IE2 was associated to breast cancer and lymph node metastasis. The expression level of estrogen receptor-α was related to HCMV infection. Show more

Keywords: Primary breast cancer, HCMV, para cancer tissues, sentinel lymph nodes, immunohistochemistry

DOI: 10.3233/CBM-170409

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 769-780, 2018

Authors: Liang, Peiqi | Miao, Miao | Liu, Zhuogang | Wang, Hongtao | Jiang, Wei | Ma, Shiyu | Li, Chuan | Hu, Rong

Article Type: Research Article

Abstract: OBJECTIVE: We undertook a single-center retrospective study to determine the relationship between CD9 and acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: In total, 112 newly diagnosed patients in our center were enrolled in the study. Their clinical information was collected and the patients werefollowed over the course of the study. Flow cytometry was used to detect the expression of CD9. RESULTS: CD9 expression was more common in B cell acute lymphoblastic leukemia (B-ALL) and patients > 40 years old. CD9-positive patients exhibited a higher BCR-ABL fusion gene positive rate and higher neutrophil counts …than CD9 negative patients (P = 0.004 and P = 0.004, respectively). Response to induction chemotherapy was not dependent on CD9 expression. CD9-positive patients had a lower 2-year overall survival rate than CD9-negative patients. CONCLUSION: CD9 expression predicts some clinical characteristics and indicates an unfavorable prognosis in ALL patients. Show more

Keywords: Acute lymphoblastic leukemia, CD9, clinical characteristics, prognosis

DOI: 10.3233/CBM-170422

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 781-786, 2018

Authors: Zhong, Li-Xia | Nie, Jun-Hua | Liu, Jia | Lin, Li-Zhu

Article Type: Research Article

Abstract: BACKGROUND: Aplysia ras homology member I/ARHI is known as ovarian cancer suppressor gene and potential inhibitor of signal transducer and activator of transcription 3/STAT3 signaling. Resveratrol suppresses growth and STAT3 activation of ovarian cancer cells, while its influence in ARHI expression remains unknown. OBJECTIVE: The current study aims to elucidate the status of ARHI expression and its relevance with growth suppression and STAT3 inactivation of resveratrol-treated cells. METHODS: ARHI expression patterns of three ovarian cancer cell lines (human CAOV-3, OVCAR-3 and rat NUTU-19) without and with 100 μ M resveratrol treatment …were checked by immunocytochemical staining, Western blotting and RT-PCR. The involvement of ARHI in the growth inhibition and STAT3 inactivation of resveratrol-treated OVCAR-3 cells was investigated by transfection of ARHI-specific siRNA. RESULTS: ARHI is expressed in low levels in three ovarian cancer cell lines, which is upregulated upon resveratrol treatment accompanied with growth arrest, extensive apoptosis, increased autophagic activity and inactivated STAT3 signaling. Specific siRNA transfection efficiently knocked down ARHI expression in resveratrol-treated CAOV-3 and OVCAR-3 cells and increased the total cell number in limited extents (P > 0.05) in comparison with that of resveratrol-treated ovarian cancer cells without any transfection or transfected with mock oligonucleotides. ARHI knockdown failed to prevent resveratrol-caused STAT3 inactivation and cell crisis. CONCLUSION: ARHI upregulation is another molecular event caused by resveratrol and one of the elements related with resveratrol’s anti-ovarian cancer efficacy. Resveratrol may inactivate STAT3 signaling of ovarian cancer cells in ARHI unrelated pattern(s). Show more

Keywords: ARHI, Resveratrol, Ovarian Cancer, STAT3 signaling, Growth suppression, siRNA transfection

DOI: 10.3233/CBM-170483

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 787-795, 2018

Authors: Zhang, Xin | Liu, Xia | Kang, Shuxia | Liu, Caiyun | Hao, Yuqin

Article Type: Research Article

Abstract: AIMS AND BACKGROUND: Squamous cell carcinoma (SCC) is one of the most common skin cancers. Photodynamic therapy (PDT) is a non-invasive treatment for SCC, but it is usually effective only on tumors just under the skin. Resveratrol (Res) is a polyphenolic compound, which is capable of promoting apoptosis of a variety of cancer cells. Res administration is non-invasive and effective on SCC, thus it may be used as an adjuvant for PDT. So far, there is no published study investigating the combination use of PDT with Res to improve clinical outcome of SCC. So in this study, we will …examine the effectiveness of combined treatment of PDT and Res as well as its underlying mechanism. METHODS: The human HaCaT keratinocytes and human A431 epidermoid carcinoma cells were treated with ALA-PDT or/and Res, and cell proliferation and apoptosis were evaluated by MTT and flow cytometry respectively afterwards. p-ERK, p38, p53 and caspase-3 protein expression was examined by western blot. Then a p38 inhibitor was added to test the involvement of p38 pathway in A431 cells responding to ALA-PDT and Res treatments. RESULTS: The results showed that Res could enhance the effect of ALA-PDT on cell proliferation and apoptosis in A431 cells. We also found that the expression of p-ERK, p-p38, p53 and caspase-3 was increased. However, inhibition of p38 pathway attenuated the effect of Res. CONCLUSION: Our study demonstrated that Res could enhance the effect of ALA-PDT against skin cancer cells through p38/ MAPK pathway. Show more

Keywords: ALA-PDT, resveratrol, squamous cell carcinoma, proliferation, apoptosis

DOI: 10.3233/CBM-170495

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 797-803, 2018

Authors: Wang, Jianjun | Liu, Yuanyuan | Sun, Wangwei | Zhang, Qinghui | Gu, Tao | Li, Guangxin

Article Type: Research Article

Abstract: Exosomes are lipid bilayer vesicles of endocytic origin ranging from 30 to 100 nm in size, and contain various nucleic acid molecules such as DNA, mRNA, miRNA, lncRNA and multiple proteins, which could be transferred into target cells. Recent study indicated that exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Increasing evidences show that exosomes play a crucial role in gastric cancer because they are potential to influence normal cellular physiology and promote various states of the cancer. In this review, we focus on the latest findings on exosomes in the …plasma of gastric cancer patients, mainly summarizing the functions of miRNAs, lncRNAs and multiple proteins in diagnosis, prognosis, and in establishing treatment regimens against gastric cancer. Furtherly, potential functions of exosomes as novel diagnostic biomarkers for gastric cancer are discussed extensively. Exosomes are believed to be a non-invasive disease biomarker with a dual capability to provide insights into the early diagnosis for gastric cancer. Show more

Keywords: Exosomes, gastric cancer, biomarker, miRNA, lncRNA

DOI: 10.3233/CBM-170738

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 805-812, 2018

Authors: Li, Zhongqi | Guo, Qi | Wei, Juying | Jin, Jie | Wang, Jinghan

Article Type: Research Article

Abstract: BACKGROUND: The prognostic value of geriatric nutritional risk index (GNRI) for diffuse large B-cell lymphoma (DLBCL) treated in the rituximab era was not clear. OBJECTIVE: To investigate the prognostic impact of GNRI in patients with DLBCL in our hospital. METHODS: DLBCL patients were recruited and classified into two groups with and without malnutrition based on GNRI. Clinical features, concentration of T-helper cell type (Th1/Th2/Th17) cytokine profiles and overall survival were compared between these two groups. RESULTS: One hundred and five (39%) out of 267 patients were classified into malnutrition group. …Patients with malnutrition had lower levels of albumin and hemoglobin, but older age, higher lactate dehydroxygenase (LDH) level, higher frequencies of advanced stage, poor performance status, B symptoms and extranodal involvement, higher scores of NCCN-IPI and higher level of INF-γ . Moreover, patients with malnutrition had poor overall survival in univariate analyses. But these significances did not stand after stratified analyses by NCCN-IPI, or in the context of NCCN-IPI in the multivariate analyses. CONCLUSIONS: GNRI is not an independent predictor for DLBCL patients. Show more

Keywords: lymphoma, nutritional risk, predictor

DOI: 10.3233/CBM-170754

Citation: Cancer Biomarkers, vol. 21, no. 4, pp. 813-820, 2018