Cancer Biomarkers - Volume 18, issue 4

Authors: Zohny, Samir F. | Baothman, Othman A. | El-Shinawi, Mohamed | Al-Malki, Abdulrahman L. | Zamzami, Mazin A. | Choudhry, Hani

Article Type: Research Article

Abstract: OBJECTIVE: We examined the expression status of p21^{Waf1/Cip1} and p57^{Kip2} in breast cancer as well as their relationship with clinicopathological factors. Moreover, the diagnostic value of gene promoter methylation of p21 ^Waf1/Cip1 and p57 ^Kip2 was assessed in breast cancer patients. METHODS: This study involved 85 patients diagnosed with breast cancer and 36 patients with benign breast lesions. The expression of p21^{Waf1/Cip1} and p57^{Kip2} in cell lysates was analyzed by ELISA and Western blot, respectively. The gene promoter methylation of p21 ^Waf1/Cip1 and p57 ^Kip2 was examined in cell lysates by methylation …specific PCR. RESULTS: p21^{Waf1/Cip1} expression was higher while p57^{Kip2} level was lower in breast cancer patients compared to patients with benign breast lesions. The combined use of p21^{Waf1/Cip1} and p57^{Kip2} provided sensitivity and specificity of 82.35% and 86.11%, respectively. None of the malignant and benign breast tumors were found to be hypermethylated at p21 ^Waf1/Cip1 gene promoter. However, aberrant methylation of p57 ^Kip2 gene promoter was detected in 49 of 85 (57.65%) of breast cancer tumors. High p21^{Waf1/Cip1} level was associated with high grade, late stages and lymph node involvement, whereas low p57^{Kip2} level was correlated with high grade and HER2 overexpressing breast cancer. Moreover, hypermethylated p57 ^Kip2 gene promoter was associated with high grade. CONCLUSION: Our findings show that the overexpression of p21^{Waf1/Cip1}, down-expression of p57^{Kip2} and gene promoter methylation of p57 ^Kip2 could be considered as promising diagnostic markers for breast cancer. Show more

Keywords: Breast cancer, p21^{Waf1/Cip1}, p57^{Kip2}, gene promoter methylation, clinicopathological factors

DOI: 10.3233/CBM-160308

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 413-423, 2017

Authors: Song, Lele | Yu, Haotian | Jia, Jia | Li, Yuemin

Article Type: Research Article

Abstract: BACKGROUND: The applications of the SEPT9 assay are expanding from CRC early diagnosis to screening, therapeutic effect monitoring and prognosis prediction. Its performance in these areas has not been thoroughly examined. OBJECTIVE: We aim to evaluate the performance of the SEPT9 assay in CRC screening, diagnosis and therapy by reviewing the current data published in these aspects. METHODS: The Ovid MEDLINE, EMBASE, CBMdisc (China Biology Medicine disc) and CJFD (Chinese Journal Full - text Database) database were searched for potential reports on the assay performance. Letters, reviews, meta-analysis and guidelines, basic research studies …and articles irrelevant to mSEPT9 detection assays were excluded. Finally, data from 19 studies was summarized and systematically reviewed to clarify the assay performance. RESULTS: 2/3 algorithm provided the best overall performance in diagnosis and screening, while the 1/3 algorithm exhibited the best sensitivity in screening. The combination of SEPT9 assay with FIT and/or CEA enhanced the CRC detection rate in screening. The SEPT9 assay appeared to be effective in monitoring the therapeutic effect and may potentially predict the CRC recurrence and survival. CONCLUSION: The SEPT9 assay exhibited satisfactory performance in CRC diagnosis and screening, while more evidence is needed for therapeutic effect monitoring and prognosis prediction. Show more

Keywords: SEPT9, Septin 9, colorectal cancer, adenoma, methylation, CEA, fecal DNA

DOI: 10.3233/CBM-160321

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 425-432, 2017

Authors: Huang, Baohua | Liu, Xiaoyan | Sun, Chengming | Wang, Lipeng | Yang, Liping

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the relationship of single nucleotide polymorphisms in the coding region of Bcl -2 with the occurrence and prognosis of colorectal cancer (CRC). METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used detect Bcl -2 gene polymorphisms (rs1800477A/G and rs1801018A/G) in 185 patients with CRC (case group) and 177 healthy subjects (control group). The relationships of Bcl -2 gene polymorphisms with clinicopathological features and prognosis of CRC patients were analyzed. RESULTS: The frequency of GG genotype and G allele of rs1800477A/G in the case group were significantly higher …than those in the control group (both P < 0.05). The GG genotype of rs1800477A/G was associated with lymph node metastasis and Dukes' staging of CRC (both P < 0.05). Haplotype analysis demonstrated that the case group had decreased frequency of GA haplotype, but increased frequency of GG haplotype in comparisons to the control group (GA: P = 0.014; GG: P = 0.003). Kaplan-Meier survival analysis showed that the risk of death (within 5 years) in patients carrying GG genotype (rs1800477A/G) was 2.159 as much as that in patients carrying AA + GA genotype. Multivariate analyses showed that Dukes' staging and GG genotype of rs1800477A/G are risk factors for poor prognosis in CRC (Dukes' staging: P = 0.001; GG genotype: P = 0.034). CONCLUSION: Bcl -2 rs1800477A/G polymorphism may be related to the occurrence of CRC, and GG genotype could be a risk factor of poor prognosis in CRC. Show more

Keywords: Colorectal cancer, Bcl-2, gene polymorphism, clinicopathological features, prognosis

DOI: 10.3233/CBM-160378

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 433-439, 2017

Authors: Akyol, Murat | Alacacioglu, Ahmet | Demir, Leyla | Kucukzeybek, Yuksel | Yildiz, Yasar | Gumus, Zehra | Kara, Mete | Salman, Tarik | Varol, Umut | Taskaynatan, Halil | Oflazoglu, Utku | Bayoglu, Vedat | Tarhan, Mustafa Oktay

Article Type: Research Article

Abstract: BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in …body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. RESULTS: There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, p< 0.001). Total body water (p< 0.001), serum glucose (p= 0.036) and triglyceride levels (p< 0.001) also exhibited a significant decrease. The decreases in total cholesterol and low-density lipoprotein were not statistically significant. Likewise, high-density lipoprotein increased after adjuvant endocrine therapy, although it did not reach statistical significance. The changes in body composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. CONCLUSION: As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer. Show more

Keywords: Breast cancer, serum FGF 21, glucose metabolism, lipid metabolism, tamoxifen, aromatase inhibitors

DOI: 10.3233/CBM-161507

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 441-449, 2017

Authors: Qi, Ming | Liu, Dongmei | Zhang, Shuhong

Article Type: Research Article

Abstract: BACKGROUND: Multidrug resistance in gastric cancer greatly impedes the efficacy of chemotherapy. OBJECTIVE: To explore the efficacy of microRNA-21 (mir-21) in distinguishing metastatic gastric cancer (MGC) with chemoresistance. METHODS: From April 2012 to May 2015, 92 MGC patients were enrolled. Cisplatin and fluorouracil-based systemic chemotherapy was given, and patients' characteristics and follow-up data were collected. In addition, miR-21 expression was determined in tumor tissue and plasma. RESULTS: Sixty-seven patients responded to chemotherapy, and chemotherapy resistance was observed in 25 patients. miR-21 expression in tumor tissue and plasma was significantly elevated …in the chemotherapy-resistant group (CRG) compared to the chemotherapy-sensitive group (CSG) (p< 0.001). miR-21 expression in tissue was associated with tumor differentiation (p= 0.042), and plasma miR-21 was correlated with gender (p= 0.016), tumor differentiation (p= 0.003), and number of metastatic sites (p< 0.001). Receiver operating characteristic (ROC) analysis indicated that miR-21 in tissue yielded an area under the ROC curve (AUC) of 0.830 (95%CI: 0.737-0.900, sensitivity: 88.0%, specificity: 68.7%) in distinguishing CRG from CSG; and plasma miR-21 yielded an AUC of 0.759 (95%CI: 0.658-0.842, sensitivity: 52.0%, specificity: 88.1%) in distinguishing CRG form CSG. Log-rank test and Cox proportional hazard regression analysis indicated that patients with higher miR-21 expression in tissue and plasma experienced shorter overall survival (P< 0.001). CONCLUSION: miR-21 could serve as a potential biomarker to identify MGC with chemoresistance. Show more

Keywords: microRNA-21, gastric cancer, biomarker, survival analysis

DOI: 10.3233/CBM-161732

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 451-458, 2017

Authors: Kurtul, Neslihan | Taşdemir, Erdem Arzu | Ünal, Dilek | İzmirli, Mustafa | Eroglu, Celalettin

Article Type: Research Article

Abstract: BACKGROUND: The aim of this study is to search the prognostic value of SPARC expression in rectum cancer cases receiving postoperative radiotherapy. METHODS: Forty three rectal cancer patients are recruited to this retrospective study. All patients received postoperative radiotherapy which the median dose was 5040 cGy and concomitant chemotherapy. Samples taken from their paraffin blocks were examined with immunohistochemical procedures. RESULTS: When the association between SPARC expression and the clinicopathological feature was examined, there was a significant association between age and expression levels. Overall survival of patients with low expression was found to …be 67 months whereas the overall survival of the patients with high expression was 32 months and the difference was statistically significant. Time to local recurrence of patients with low expression was found to be 74 months whereas time to local recurrence of the patients with high expression was 31 months. Progression free survival of the patients with low expression and high expression were 67 months and 32 months, respectively. In multivariate Cox regression analyses, high expression of SPARC was found to be associated with a statistically significant shorter overall survival and progression free survival. CONCLUSIONS: High expression of SPARC is related to worse prognosis in rectal cancer patients. Show more

Keywords: Prognosis, rectal cancer, SPARC

DOI: 10.3233/CBM-161733

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 459-466, 2017

Article Type: Other

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 467-472, 2017