Shi-Ting Huang

Identification of genes involved in radioresistance of nasopharyngeal carcinoma by integrating gene ontology and protein-protein interaction networks.

Radioresistance remains one of the important factors in relapse and metastasis of nasopharyngeal carcinoma. Thus, it is imperative to identify genes involved in radioresistance and explore the underlying biological processes in the development of radioresistance. In this study, we used cDNA microarrays to select differential genes between radioresistant CNE-2R and parental CNE-2 cell lines. One hundred and eighty-three significantly differentially expressed genes (p<0.05) were identified, of which 138 genes were upregulated and 45 genes were downregulated in CNE-2R. We further employed publicly available bioinformatics related software, such as GOEAST and STRING to examine the relationship among differentially expressed genes. The results show that these genes were involved in type I interferon-mediated signaling pathway biological processes; the nodes tended to have high connectivity with the EGFR pathway, IFN-related pathways, NF-κB. The node STAT1 has high connectivity with other nodes in the protein-protein interaction (PPI) networks. Finally, the reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and Western blotting. The results were consistent with the microarray data. Our study suggests that microarrays combined with gene ontology and protein interaction networks have great value in the identification of genes of radioresistance in nasopharyngeal carcinoma; genes involved in several biological processes and protein interaction networks may be relevant to NPC radioresistance; in particular, the verified genes CCL5, STAT1-α, STAT2 and GSTP1 may become potential biomarkers for predicting NPC response to radiotherapy.

Poly(ADP-ribose) polymerase-1 regulates the mechanism of irradiation-induced CNE-2 human nasopharyngeal carcinoma cell autophagy and inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells

The aim of the present study was to investigate the role of autophagy in response to ionizing radiation (IR) in CNE-2 human nasopharyngeal carcinoma cells and to demonstrate the function of poly(ADP-ribose) polymerase-1 (PARP-1) in the regulation of IR-induced autophagy. Microtubule-associated protein 1 light chain 3 (LC3) and poly(ADP-ribose) (PAR) were assessed using western blotting. Ultrastructural analysis was performed using transmission electron microscopy (TEM). The percentage of apoptotic cells was assessed by flow cytometry. The MTT method was used to detect cell viability of CNE-2 cells at different time points after IR. Clonogenic survival assays were used to evaluate the radiosensitivity of nasopharyngeal carcinoma cells treated with IR and IR combined with autophagy inhibitor (chloroquine phosphate), with autophagy inducer (rapamycin) or with PARP-1 inhibitor 3-amino benzamide (3AB). IR induced a massive accumulation of autophagosomes detected by TEM and intensified the conversion of cytosolic LC3-I to LC3-II. PARP-1 activation was accompanied by strong upregulation of PAR and LC3-II expression in CNE-2 cells. Compared with radiation alone, chloroquine phosphate (CDP) or 3AB combined with IR significantly decreased cell viability, as well as the autophagic ratio and LC3-II protein levels. Inhibition of autophagy increased radiation-induced apoptosis; rapamycin (RAPA) significantly decreased cell viability as well, but RAPA increased the autophagic ratio and LC3-II protein levels; induction of autophagy increased radiation-induced apoptosis. To conclude, PARP-1 regulates IR-induced autophagy, and PARP-1 inhibitor contributes to the radiation sensitization of CNE-2 cells. Blockade of autophagy with CDP enhanced the cytotoxicity of radiotherapy in CNE-2 cells. This suggests that inhibition of autophagy or PARP-1 may be used as an adjuvant therapy to treat nasopharyngeal carcinoma.

Identification of Radioresistance-Associated Proteins in Human Nasopharyngeal Carcinoma Cell Lines by Proteomic Analysis

BACKGROUND AND PURPOSE Radiotherapy is the mainstay of treatment modality for human nasopharyngeal carcinoma (NPC), but in some cases, the disease is radioresistant. This study aimed to identify proteins potentially responsible for radioresistance of NPC by a proteomic approach. MATERIAL AND METHODS The radioresistant human NPC cell line CNE-2R and its parental cell line CNE-2 were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/time-of-flight mass spectrometry analysis. The candidate proteins were validated by Western blot analysis. RESULTS In total, 16 differentially expressed proteins were identified; among them, Nm23 H1 was significantly increased, while Annexin A3 was significantly downregulated in CNE-2R cells, compared to CNE-2 cells. CONCLUSIONS Our findings provide a platform for further characterization of the proteins implicated in radioresistance and suggest that these proteins could be exploited as a biomarker for predicting the NPC response to radiotherapy in the clinic.

Systematic review and meta-analysis of the efficacy of breast conservation therapy followed by radiotherapy in four breast cancer subtypes

The different molecular subtypes of breast cancer are associated with distinct outcomes. We assessed the efficacy of breast conservation therapy (BCT) followed by radiotherapy for patients with different breast cancer subtypes. We searched the MEDLINE, EMBASE, and Cochrane Library databases to identify studies published prior to April 30, 2016 that assessed the efficacy of BCT followed by radiotherapy in breast cancer patients with different molecular subtypes. A meta-analysis of seven studies that included 3,798 luminal A, 770 luminal B, 344 human epidermal growth factor receptor 2 (Her-2), and 767 triple-negative breast cancer (TNBC) patients was performed. The pooled odds ratio [OR] for local relapse-free survival in luminal A compared to Her-2 patients was 0.1960 (95% confidence interval [CI]: 0.0440–0.8728, p = 0.0325) at 5 years and 0.2592 (95% CI: 0.1301–0.5167, p = 0.0001) at 10 years. The pooled OR for local-regional relapse-free survival in luminal A compared to TNBC patients was 0.1381 (95% CI: 0.0565–0.3374, p = 0.0000) at 5 years and 0.1221 (95% CI: 0.0182–0.8192, p = 0.0304) at 10 years. Thus, the rate of local-regional control is higher in luminal A patients than in Her-2 or TNBC patients.The different molecular subtypes of breast cancer are associated with distinct outcomes. We assessed the efficacy of breast conservation therapy (BCT) followed by radiotherapy for patients with different breast cancer subtypes. We searched the MEDLINE, EMBASE, and Cochrane Library databases to identify studies published prior to April 30, 2016 that assessed the efficacy of BCT followed by radiotherapy in breast cancer patients with different molecular subtypes. A meta-analysis of seven studies that included 3,798 luminal A, 770 luminal B, 344 human epidermal growth factor receptor 2 (Her-2), and 767 triple-negative breast cancer (TNBC) patients was performed. The pooled odds ratio [OR] for local relapse-free survival in luminal A compared to Her-2 patients was 0.1960 (95% confidence interval [CI]: 0.0440-0.8728, p = 0.0325) at 5 years and 0.2592 (95% CI: 0.1301-0.5167, p = 0.0001) at 10 years. The pooled OR for local-regional relapse-free survival in luminal A compared to TNBC patients was 0.1381 (95% CI: 0.0565-0.3374, p = 0.0000) at 5 years and 0.1221 (95% CI: 0.0182-0.8192, p = 0.0304) at 10 years. Thus, the rate of local-regional control is higher in luminal A patients than in Her-2 or TNBC patients.

Secondary malignancies after partial versus whole breast irradiation: a systematic review and meta-analysis.

Secondary malignancies are a common complication for patients receiving radiotherapy. Here, we compared rates of secondary malignancies after partial breast irradiation (PBI) and whole breast irradiation (WBI). The MEDLINE, EMBASE, and the Cochrane Library databases were systematically searched to identify relevant randomized clinical trials comparing PBI with WBI in breast cancer patients treated with breast-conserving therapy. Four studies including 2,185 patients were selected. Compared to WBI, the pooled odds ratios (OR) for contralateral breast cancer were 0.86 (95% confidence interval (CI) 0.31–2.42; p = 0.78) after 5 years and 1.15 (95% CI 0.43-3.09; p = 0.78) after 10 years for PBI. The pooled ORs for secondary non-breast cancer were 0.91 (95% CI 0.49-1.67; p = 0.77) after 5 years and 1.20 (95% CI 0.39-3.66; p = 0.75) after 10 years for PBI compared to WBI. These results demonstrate that the risk of secondary malignancies is similar for PBI and WBI after breast-conserving radiotherapy.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in intensity modulated radiation therapy for nasopharyngeal carcinoma

Background Inflammatory response markers plays an important role in tumor progression. The aim of this analysis was to evaluate whether the neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) could predict the prognosis of nasopharyngeal carcinoma(NPC). Materials and Methods 247 patients who underwent Intensity Modulated Radiation Therapy( IMRT )were enrolled from January 2012 and December 2012. NLR, and PLR were calculated from peripheral blood cell counts taken at pre-treatment. Optimal cutoff values of NLR and PLR were determined on the basis of receiver operating characteristic curve analysis. Overall survival (OS), progression-free survival(PFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival ( LRFS) rates were compared according to NLR and PLR level respectively. Multivariate analysis was performed to assess the prognostic value of NLR and PLR. Results The 5-year estimated OS, PFS, LRFS and DFS were 87.2, 77.8, 96.9, and 86.2%, respectively. Our results shows that the NLR was significantly associated with T-stage (P < 0.05), N-stage (P < 0.05) and tumor stage(P < 0.05). PLR was significantly associated with T-stage (P < 0.05) and tumor stage(P < 0.05). NLR was an independent prognostic indicator for OS (HR: 3.259, P = 0.004), PFS (HR:7.093, P < 0.001), DMFS (HR: 6.576, P = 0.003), except for PLR. In subgroup analysis, adjuvant chemotherapy had no significantly improved survival for patients with high NLR. Conclusions NLR is a strong prognostic factor for NPC patients. NLR might not be a useful indicator for selection of treatment strategies for loco-regionally advanced NPC.

Prognostic Nomogram for Overall Survival in Extranodal Natural Killer/T-Cell Lymphoma Patients

Background: Extranodal natural killer/T‐cell lymphoma (ENKTL) is a rare lymphoid malignancy with diverse clinical features and prognoses. The aims of this study were to explore the pretreatment prognostic factors of ENKTL and develop a new individual prognostic model. Patients and Methods: We retrospectively enrolled 81 ENKTL patients with newly diagnosed disease between June 2006 and August 2017 at the Affiliated Cancer Hospital of Guangxi Medical University. Survival analysis was used to assess the prognostic value of various factors. A nomogram was developed to predict overall survival (OS) based on the Cox proportional hazards model. Results: The median survival time of the patients was 48 months, and the 5‐year OS rate was 47.5%. Cox regression analysis showed that the prognostic factors of OS for ENKTL patients included Eastern Cooperative Oncology Group performance status, Ann Arbor stage, pretreatment albumin‐to‐globulin ratio, and platelet count. A prognostic nomogram was developed to predict the OS rate for ENKTL patients based on these factors. The calibration curve showed that the nomogram was able to predict OS accurately. The concordance index of the nomogram for OS prediction was 0.807. Conclusion: Our proposed nomogram based on Eastern Cooperative Oncology Group performance status, Ann Arbor stage, albumin‐to‐globulin ratio, and platelet count provides an individualized risk estimate of OS in patients with ENKTL.

Comparison of the efficacy between intensity-modulated radiotherapy and two-dimensional conventional radiotherapy in stage II nasopharyngeal carcinoma

We compared treatment outcomes in patients with stage II nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT). Stage II (2010 UICC/AJCC staging system) NPC patients treated with IMRT (n = 178) or 2D-CRT (n = 73) between January 2007 and December 2014 were retrospectively analyzed. Patients were matched using the propensity score-matching method. The primary endpoint was overall survival (OS). Secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Acute and late toxicity reactions to IMRT and 2D-CRT were also compared. In an unmatched cohort of 251 patients, no significant survival differences were found between those receiving IMRT and those receiving 2D-CRT (5-year OS, 95.67% vs 94.44%, P = 0.0556; LRFS, 97.34% vs 98.59%, P = 0.6656; RRFS, 99.26% vs 100%, P = 0.6785; DMFS, 96.5% vs 98.63%, P = 0.7910; DFS, 92.2% vs 97.24%, P = 0.8719). In the propensity-matched cohort of 146 patients, 5-year OS (97.06% vs 94.44%, P = 0.1325), LRFS (96.75% vs 98.59%, P = 0.8869), RRFS (100% vs 100%, P = 1.0000), DMFS (98.63% vs 98.63%, P = 0.4225), and DFS (95.37% vs 97.24%, P = 0.5634) were similar between patients treated with IMRT or 2D-CRT. However, IMRT correlated with fewer acute and late toxicity reactions. Thus although IMRT provides no survival advantage, it has a lower incidence of toxicity than 2D-CRT in stage II NPC patients.We compared treatment outcomes in patients with stage II nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT). Stage II (2010 UICC/AJCC staging system) NPC patients treated with IMRT (n = 178) or 2D-CRT (n = 73) between January 2007 and December 2014 were retrospectively analyzed. Patients were matched using the propensity score-matching method. The primary endpoint was overall survival (OS). Secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Acute and late toxicity reactions to IMRT and 2D-CRT were also compared. In an unmatched cohort of 251 patients, no significant survival differences were found between those receiving IMRT and those receiving 2D-CRT (5-year OS, 95.67% vs 94.44%, P = 0.0556; LRFS, 97.34% vs 98.59%, P = 0.6656; RRFS, 99.26% vs 100%, P = 0.6785; DMFS, 96.5% vs 98.63%, P = 0.7910; DFS, 92.2% vs 97.24%, P = 0.8719). In the propensity-matched cohort of 146 patients, 5-year OS (97.06% vs 94.44%, P = 0.1325), LRFS (96.75% vs 98.59%, P = 0.8869), RRFS (100% vs 100%, P = 1.0000), DMFS (98.63% vs 98.63%, P = 0.4225), and DFS (95.37% vs 97.24%, P = 0.5634) were similar between patients treated with IMRT or 2D-CRT. However, IMRT correlated with fewer acute and late toxicity reactions. Thus although IMRT provides no survival advantage, it has a lower incidence of toxicity than 2D-CRT in stage II NPC patients.

Intensity-modulated radiotherapy provides better quality of life than two-dimensional conventional radiotherapy for patients with stage II nasopharyngeal carcinoma

Two-dimensional conventional radiotherapy (2D-CRT) and intensity-modulated radiotherapy (IMRT) are effective for control of nasopharyngeal carcinoma (NPC). The purpose of this study was to compare the quality of life (QoL) of stage II NPC patients treated with 2D-CRT versus IMRT. We conducted a cross-sectional study of 106 patients with stage II NPC treated with 2D-CRT (n = 47) versus IMRT (n = 59) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. Patients receiving IMRT with or without concurrent chemotherapy had better outcomes in head and neck related symptoms and general aspects of QoL than those receiving 2D-CRT with or without concurrent chemotherapy. Thus, IMRT improves the QoL of patients with stage II NPC as compared to 2D-CRT.

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy.