Cancer Biomarkers - Volume 20, issue 3

Authors: Ma, Yan | Dai, Huan-Yu | Zhang, Feng | Zhao, Da

Article Type: Research Article

Abstract: OBJECTIVE: The tripartite motif-containing protein (TRIM) family is involved in important biological processes such as the cell cycle, cell apoptosis, and innate immunity of virus. This study aimed to investigate TRIM66 expression and its predictive role in non-small cell lung cancer (NSCLC) patients. METHODS: We detected the expression levels of TRIM66 protein and TRIM66 mRNA in NSCLC tissues, and evaluated the prognostic role of TRIM66 in NSCLC. RESULTS: TRIMM66 was highly expressed in NSCLC tissues compared with normal paracancerous tissues (P = 0.001). The high TRIM66 expression closely associated …with lymph node metastasis and TNM stage in NSCLC patients (P < 0.05). Kaplan-Meier survival model indicated that survival time of NSCLC patients in the high TRIM66 expression group were markedly lower than those in the low expression group (P < 0.05). Cox regression analysis showed that high expression of TRIM66 is associated with poor prognosis in NSCLC patients. CONCLUSION: TRIM66 can be serve as an important molecular marker for predicting the prognosis in NSCLC patients. Show more

Keywords: Non-small cell lung cancer, TRIM66, expression, prognosis

DOI: 10.3233/CBM-170207

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 309-315, 2017

Authors: Yao, Rong | Pu, Juan | Fan, Ruihua | Zhu, Weiguo | Ding, Xiaorong | Shen, Xiaoying | Zhang, Tiecheng

Article Type: Research Article

Abstract: Our study mainly investigated ubiquitin-specific protease 4 (USP4) expression in pathogenesis of esophageal cancer. The data showed significantly increased expression of USP4 in cancer tissues compared to that in para-carcinoma tissues (68.38% ± 25.60% vs 13.04% ± 9.95%, P = 0.000) and positive correlation between USP4 and pathology grade (r = 0.249, P = 0.014), although survival analysis revealed that USP4 expression was positively associated with the prognosis (32.4% vs 10.9%, P = 0.043). …Grouped analysis revealed that the prognosis of patients with high USP4 expression were significantly better only in the small tumor subgroup (diameter ⩽ 5 cm) (52.6% VS 8.6%, P = 0.001) and the early stage subgroup (stages 1 and 2) (60.0% VS 16.7%, P = 0.006). Moreover, in the subgroup of clinical stages 1 and 2 with tumor diameter ⩽ 5 cm, high USP4 expression prolonged the survival time of esophageal cancer patients more significantly (75.5% VS 5.9%, P = 0.000). Based on these results, we speculated that it was possible to significantly improve the prognosis of patients with low USP4 expression by targeted therapy in early esophageal cancer. Taken together, our study uncovered a previously unknown function of USP4 in esophageal cancer and more investigations would be carried out to further study its regulation gene network and molecular biological mechanism in esophageal cancer. Show more

Keywords: Tissue microarray, immunohistochemistry, USP4, esophageal cancer, prognosis

DOI: 10.3233/CBM-170308

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 317-323, 2017

Authors: Xie, Rui | Wu, Shang-Nong | Gao, Cheng-Cheng | Yang, Xiao-Zhong | Wang, Hong-Gang | Zhang, Jia-Ling | Yan, Wei | Ma, Tian-Heng

Article Type: Research Article

Abstract: BACKGROUND: microRNA (miR)-1290 was previously indicated to promote esophageal squamous cell carcinoma (ESCC) progression via regulating its target gene nuclear factor I/X (NFIX). OBJECTIVE: To investigate clinical significance of miR-1290 and NFIX in ESCC. METHODS: Quantitative real-time PCR was performed to detect miR-1290 and NFIX mRNA expression in ESCC tissues. Associations of miR-1290 and/or NFIX mRNA expression with various clinicopathological features and prognosis in ESCC patients were statistically evaluated. RESULTS: Compared to noncancerous esophageal mucosa, miR-1290 expression was upregulated, while NFIX mRNA expression was downregulated in ESCC tissues. There was …a significantly negative correlation between miR-1290 and NFIX expression in ESCC tissues (r = - 0.427, P = 0.01). Interestingly, miR-1290-high and/or NFIX-low expression were all significantly associated with positive lymph node metastasis and advanced tumor-node-metastasis stage of ESCC patients (all P < 0.05). Moreover, miR-1290 upregulation and NFIX downregulation both correlated short overall and disease-free survivals of ESCC patients. Importantly, the prognostic value of combined miR-1290 and NFIX expression was more significant than those considered alone. CONCLUSIONS: Our data suggest that the dysregulation of miR-1290-NFIX axis may play crucial roles in esophageal carcinogenesis and progression. We also confirmed miR-1290 and its target gene NFIX as independent prognostic factors for ESCC patients. Show more

Keywords: Esophageal squamous cell carcinoma, microRNA-1290, nuclear factor i/X, prognosis, clinicopathological characteristics

DOI: 10.3233/CBM-170029

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 325-331, 2017

Authors: Najjar, Fadi | Alammar, Moocheer | Al-Massarani, Ghassan | Almalla, Nissreen | Aljapawe, Abdulmunim | Ikhtiar, Adnan

Article Type: Research Article

Abstract: BACKGROUND: Circulating endothelial cells (CECs) and microparticles (MPs) are proposed as useful biosensors for angiogenesis and membrane damage in cancer. OBJECTIVE: We investigated their predictive value for progression disease (PD) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy. METHODS: Peripheral blood samples were obtained from 60 patients. Immunomagnetic separation (IMS) and flow cytometry techniques were used to quantify CECs and MPs, respectively. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values for CECs and MPs counts according to their levels in patients …with an objective response (OR) and non-responders after treatment. Baseline serum biomarkers levels and their kinetics after chemotherapy were correlated with tumor response and outcomes in advanced NSCLC patients. RESULTS: Forty-seven patients presented an OR after chemotherapy. Of these, 28 patients progressed within three months. Through an increase in their levels during or after chemotherapy, CECs and MPs correctly predicted PD in 57% and 61% of these patients, respectively. Regarding tumor stage, NSCLC patients with stage IV had significantly higher pretreatment CECs and MPs levels than stage III patients (p = 0.037 and 0.018, respectively). Moreover, progression-free survival (PFS) was significantly longer in patients with high baseline CECs levels than those with low pretreatment CECs values (p = 0.05). Moreover, patients with high percentage change in CECs count after chemotherapy had significantly longer time to progression (TTP) duration (p = 0.018). CONCLUSIONS: Our findings suggest the increase in CECs and MPs number during or after chemotherapy as predictive biomarkers of tumor progression in advanced NSCLC patients. An association of basal CECs and MPs values with tumor stage was also shown in advanced NSCLC patients. However, baseline CECs levels and their kinetics after chemotherapy seem to be prognostic factors in advanced NSCLC. Show more

Keywords: Circulating endothelial cells, microparticles, non-small cell lung cancer, chemotherapy, biomarkers, tumor progression

DOI: 10.3233/CBM-170130

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 333-343, 2017

Authors: Hou, Xiaohui | Liu, Rui | Huang, Canhua | Jiang, Lu | Zhou, Yu | Chen, Qianming

Article Type: Research Article

Abstract: Oral submucous fibrosis (OSF) is a chronic insidious disease which predisposes to oral cancer. Understanding the molecular markers for OSF is critical for diagnosis and treatment of oral cancer. In this study, the proteins expression profile of OSF tissues was compared to normal mucous tissues by 2 dimensional electrophoresis (2-DE). The 2-DE images were analyzed through cut, spot detection and match analysis using mass spectrometry (MS). Differentially expressed genes were identified as candidates. RT-PCR, Western Blot and immunohistochemistry were performed to validate the difference in expression of the candidates between OSF and normal mucous tissues. The shRNA targeted to the …candidates were then transfected by Lipofectamine2000 to the 3T3 cells to study gene function. Cell proliferation and apoptosis were measured by MTT, clonogenic formation, PI and TUNEL staining. From the proteomic analysis, 94 of the 182 selected spots with differential expression were identified by MS analysis and Cyclophilin A (CYPA) was determined to be the OSF-associated protein candidate. The significant differences in expression between OSF and normal tissues were verified and confirmed by RT-PCR, Western blot and Immunohistochemical analysis. Inhibition of CYPA expression by RNA interference suggested its potential activities involved in cell proliferation and apoptosis process. In conclusion, these results indicated a novel molecular mechanism of OSF pathogenesis and demonstrated CYPA as a potential biomarker and gene intervention targets of OSF. These data may help the development for therapeutics of oral cancer. Show more

Keywords: Oral submucous fibrosis, proteomics, 2-D electrophoresis, mass spectrum, Cyclophilin A, small hairpin RNA

DOI: 10.3233/CBM-170142

Citation: Cancer Biomarkers, vol. 20, no. 3, pp. 345-356, 2017