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// San-Gang Wu 1, * , Wen-Weng Zhang 2, * , Jia-Yuan Sun 2 , Feng-Yan Li 2 , Huan-Xin Lin 2 , Juan Zhou 3 and Zhen-Yu He 2 1 Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 2 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China * These authors have contributed equally to this work Correspondance to: Juan Zhou, email: juanzhou12345@163.com Zhen-Yu He, email: hezhy@sysucc.org.cn Keywords: breast cancer, SEER program, surgery, subtype, survival Received: February 20, 2017 Accepted: June 04, 2017 Published: June 29, 2017 ABSTRACT This retrospective study aimed to investigate the clinical value of local surgery in stage IV BC and determined whether the survival outcomes were affected by the breast cancer subtype (BCS). Women with de novo stage IV BC from 2010 to 2013 were included using the Surveillance Epidemiology and End Results database. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic factors for breast cancer-specific survival (BCSS) and overall survival (OS). Among 9,256 patients were identified, 3,130 (33.8%) were received local surgery. Patients with hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- subtype were less likely to receive local surgery, while HR-/HER2- tumors were more likely to receive surgery. Multivariate analyses revealed that local surgery improved survival, surgical intervention was an independent favorable prognostic factor for BCSS (P < 0.001) and OS (P < 0.001). Patients who receipt of surgery had better survival outcomes compared with the non-surgery group, and the survival benefits of local surgery were not affected by the BCS status. Local surgery was improved survival for patients with stage IV BC regardless of the BCS status.

// Juan Zhou 1, * , San-Gang Wu 2, * , Jia-Yuan Sun 3, * , Li-Ying Tang 4 , Huan-Xin Lin 3 , Feng-Yan Li 3 , Qiong-Hua Chen 1 , Xin Jin 5 and Zhen-Yu He 3 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 3 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 4 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College of Xiamen University, Xiamen, People’s Republic of China 5 Faculty of Basic Medicine, Medical College, Xiamen University, Xiamen, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Xin Jin, email: xinjin@xmu.edu.cn Zhen-Yu He, email: hezhy@sysucc.org.cn Keywords: cervical carcinoma, small cell, survival, prognosis Received: June 06, 2016 Accepted: March 03, 2017 Published: March 21, 2017 ABSTRACT To investigate the clinicopathological characteristics and survival of small cell carcinoma of the cervix using Surveillance, Epidemiology, and End Results database. Patients with a diagnosis of small cell carcinoma of the cervix were included between 1988 and 2012. Kaplan-Meier method and Cox regression models were used. A total of 487 patients were included. Of the patients with known International Federation of Gynecology and Obstetrics stage and tumor grade, the stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly or undifferentiated histology. The 5-year cause specific survival and overall survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing age, advanced stage, and treatment by primary radiotherapy were associated with worse survival outcomes. Small cell carcinoma of the cervix is a rare disease with aggressive characteristics and prone to metastasize and is dismal in prognosis. Reduced survival was associated with increasing age, advanced stage, and treatment by primary radiotherapy.

// Juan Zhou 1, * , San-Gang Wu 2, * , Jia-Yuan Sun 3, * , Xu-Lin Liao 4 , Feng-Yan Li 3 , Huan-Xin Lin 3 , Li-Chao Yang 5 , Zhen-Yu He 3 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 2 Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 3 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 4 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China 5 Faculty of Basic Medicine, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China * These authors contributed equally to this work Correspondence to: Li-Chao Yang, email: yanglichaoxmu@163.com Zhen-Yu He, email: hezhy@sysucc.org.cn Keywords: cervical cancer, positive lymph nodes, TNM, tumor histology, survival Received: November 07, 2016 Accepted: January 27, 2017 Published: February 09, 2017 ABSTRACT To determine the prognostic value of the number of positive lymph nodes (LNs) in cervical cancer and further stratify patients with positive LNs into multiple risk groups based on analysis of Surveillance Epidemiology and End Results (SEER) program. Patients with cervical cancer who undergo hysterectomy and had pathologically-confirmed positive LNs after lymphadenectomy were identified using the SEER database (1988-2012). Kaplan–Meier survival methods and Cox proportional hazards regression were performed. We included 2,222 patients with the median number of removed LNs and positive LNs was 22 and 2, respectively. Multivariable Cox analysis showed patients with > 2 positive LNs had poorer cause-specific survival (CSS) (hazard ratio [HR] 1.631, 95% confidence interval [CI] 1.382–1.926, P 2 positive LNs, respectively. The number of positive LNs had prognostic value in cervical squamous cell carcinoma or adenosquamous carcinoma, but not in cervical adenocarcinoma. The number of positive LNs is an independent risk factor for CSS and OS in cervical cancer. This new category might be helpful in better prognostic discrimination of node-positive early stage cervical cancer after hysterectomy.

// San-Gang Wu 1, * , Jia-Yuan Sun 2, * , Li-Chao Yang 3, * , Li-Ying Tang 4 , Xue Wang 4 , Xue-Ting Chen 4 , Gui-Hua Liu 5 , Huan-Xin Lin 2 , Qin Lin 1 , Zhen-Yu He 2 1 Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 3 Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China 4 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of China 5 School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Qin Lin, email: linqin05@163.com Zhen-Yu He, email: hezhy@sysucc.org.cn Keywords: breast cancer, breast cancer subtype, distant metastasis, patterns Received: December 25, 2015 Accepted: May 20, 2016 Published: June 16, 2016 ABSTRACT To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) − (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2−); HR+/HER2+ (ER+ and/or PR+, HER2+), HR−/HER2+ (ER− and PR−, and HER2+); and HR−/HER2− (ER− and PR−, and HER2−). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−, respectively. Patients with HR+/HER2+ and HR−/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2− and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR−/HER2− subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.

// Juan Zhou 1, * , Qiong-Hua Chen 1, * , San-Gang Wu 2, * , Zhen-Yu He 3 , Jia-Yuan Sun 3 , Feng-Yan Li 3 , Huan-Xin Lin 3 , Ke-Li You 4 1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 3 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 4 Department of Gynecology, GuangDong General Hospital, Guangzhou, People’s Republic of China * These authors contributed equally to this work Correspondence to: Ke-Li You, email: diagnosis@163.com Keywords: cervical cancer, lymph node ratio, postoperative radiotherapy, survival, SEER Received: November 28, 2015 Accepted: March 28, 2016 Published: April 18, 2016 ABSTRACT The standard treatment for node-positive cervical cancer after radical hysterectomy is pelvic radiotherapy and concurrent chemotherapy. Given the potential toxicity of postoperative radiotherapy, we used the lymph node ratio (LNR) to assess the benefit of postoperative radiotherapy in lymph node-positive cervical cancer patients. Data from the Surveillance Epidemiology and End Results database (1988–2010) were analyzed using Kaplan–Meier and Cox regression proportional hazard analysis. A total of 2,269 eligible patients were identified (median follow-up, 78.0 months); 1,863 (82.1%) patients received postoperative radiotherapy. In both univariate and multivariate analysis multivariate analysis, a higher LNR was significantly associated with a poorer outcome. A LNR > 0.16 was associated with poorer cervical cancer-related survival (CCSS) (hazard Ratio [HR] 1.376, confidence interval [CI] 1.082–1.750; P 0.16 (CCSS, P 0.16.

E2F transcription factors are involved in cell cycle regulation and synthesis of DNA in mammalian cells, and simultaneously play important roles in the development and progression of cancer when dysregulated. E2F8, a novel identified E2F family member, was found to be associated with the progression of several human cancers; however, the biological role and clinical significance of E2F8 in breast cancer remain to be further elucidated. Herein, we report that E2F8 is robustly elevated in breast cancer cell lines and clinical breast cancer tissue samples, respectively. The high expression level of E2F8 significantly correlates with clinical progression (P = 0.001), poor patient survival (P < 0.001) and a high Ki67 staining index (P = 0.008) in 187 human breast cancer specimens. Furthermore, we find that overexpressing E2F8 promotes, whereas silencing E2F8 suppresses, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. We further demonstrate that E2F8 transcriptionally upregulates CCNE1 and CCNE2 via directly interacting with their respective gene promoter, which accelerates the transition of G1 to S phase of breast cancer cells. Taken together, these findings uncover a novel biologic role and regulatory mechanism of E2F8 responsible for the progression of breast cancer, indicating E2F8 may represent a novel prognostic biomarker and therapeutic target against breast cancer.

To compare the log odds of positive lymph nodes (LODDS) with the number of positive lymph nodes (pN), lymph node ratio (LNR), removed lymph node (RLN) count, and negative lymph node (NLN) count in determining the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. The records of patients with ESCC who received esophagectomy were retrospectively reviewed. The log-rank test was used to compare curves for overall survival (OS), and Cox regression analysis was performed to identify prognostic factors. The prognostic performance of the different lymph node staging systems were compared using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion. A total of 589 patients were enrolled. Univariate Cox analysis showed that pN stage, LNR, RLN count, NLN count, and the LODDS were significantly associated with OS (p < 0.05 for all). Multivariate Cox analysis adjusted for significant factors indicated that LODDS was independent risk factor on overall survival (OS), and a higher LODDS was associated with worse OS (hazard ratio = 3.297, 95% confidence interval: 2.684-4.050, p < 0.001). The modified Tumor-LODDS-Metastasis staging system had better discriminatory ability, monotonicity, and homogeneity, and better optimistic prognostic stratification than the Tumor-Node-Metastasis staging system in determining the prognosis of patients with ESCC. The LODDS staging system was superior to other lymph node classifications in determining the prognosis of patients with ESCC after esophagectomy. LODDS may be incorporated into esophageal staging system if these results are eventually confirmed by other studies.

// San-Gang Wu 1, * , Zhao-Qiang Zhang 2, * , Wen-Ming Liu 3, * , Zhen-Yu He 4 , Feng-Yan Li 4 , Huan-Xin Lin 4 , Jia-Yuan Sun 4 , Hui Lin 5 , Qun Li 4 1 Department of Radiation Oncology, the First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 2 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College of Xiamen University, Xiamen 361003, People’s Republic of China 3 Department of Gastroenterology, Zhongshan Hospital of Xiamen University, Xiamen 361003, People’s Republic of China 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, People’s Republic of China 5 Department of Cardiovascular and Thoracic Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China * These authors contributed equally to this work Correspondence to: Hui Lin, e-mail: linhui33622@sina.com Qun Li, e-mail: liqun0799@126.com Keywords: esophageal cancer, lymph nodes, preoperative radiotherapy, survival, SEER Received: October 29, 2015 Accepted: February 24, 2016 Published: March 16, 2016 ABSTRACT To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer-directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan–Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy ( P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11–71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603–0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636–0.824, P < 0.001) than patients with 1–10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1–10 RLNs and 11–71 RLNs, respectively ( P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1–10 RLNs and 11–71 RLNs, respectively ( P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery.

// Tian-Hao Liu 1, 2, * , Fang Zheng 1, 3, * , Mu-Yan Cai 1, 5, * , Lin Guo 1, 4 , Huan-Xin Lin 1 , Jie-Wei Chen 1, 5 , Yi-Ji Liao 1 , Hsiang-Fu Kung 1 , Yi-Xin Zeng 1 , Dan Xie 1, 5 1 Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China 3 Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China 4 Department of Nasopharyngeal Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China 5 Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Dan Xie, e-mail: xiedan@sysucc.org.cn Keywords: nasopharyngeal carcinoma, ARHGEF3, BIRC8, apoptosis, pathogenesis Received: September 06, 2015 Accepted: March 06, 2016 Published: March 23, 2016 ABSTRACT Nasopharyngeal carcinoma (NPC) is one of the most prevalent forms of highly invasive malignancy in Southern China and Southeast Asia. The pathogenesis of NPC is a multistep process driven by the acquisition of numerous genetic abnormalities. We investigated the potential oncogenic role of the Rho-guanine nucleotide exchange factor 3 gene, ARHGEF3 , in NPC pathogenesis. Expression levels of ARHGEF3 were frequently up-regulated in NPC cell lines and tissues. In a large cohort of clinical NPC tissues high expression of ARHGEF3 was positively associated with an increased T status, distant metastasis, and a more advanced clinical stage ( P < 0.05). Survival analysis revealed that ARHGEF3 expression was a significant and independent prognosis factor for NPC patients. In NPC cell lines, knockdown of ARHGEF3 was sufficient to inhibit cell growth, motility, and invasion in vitro , whereas ectopic overexpression of ARHGEF3 substantially enhanced NPC cells tumorigenesis and metastasis in vivo . Depletion of ARHGEF3 in NPC cells dramatically promoted caspase-3 induced apoptosis and an anti-apoptosis factor, BIRC8 , was identified as a critical downstream target of the ARHGEF3 . Our findings suggest that increased expression of ARHGEF3 plays a critical oncogenic role in NPC pathogenesis by preventing cell apoptosis through the up-regulation of BIRC8 , and ARHGEF3 might be employed as a novel prognostic marker and effective therapeutic target for human NPC.

// Juan Zhou 1,* , Zhen-Yu He 2,* , Feng-Yan Li 2,* Jia-Yuan Sun 2 , Huan-Xin Lin 2 , San-Gang Wu 3 and Qiong-Hua Chen 1 1 Xiamen Cancer Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China 2 Sun Yat-sen University Cancer Center, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People’s Republic of China 3 Xiamen Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China * These authors have contributed equally to this work Correspondence to: San-Gang Wu, email: // Qiong-Hua Chen, email: // Keywords : epithelial ovarian cancer, lymph node ratio, positive lymph nodes, prognosis, SEER Received : September 04, 2015 Accepted : January 04, 2016 Published : January 13, 2016 Abstract To assess the prognostic value of the lymph node ratio (LNR) in patients with stage IIIC epithelial ovarian cancer (EOC) with node-positive in a Surveillance, Epidemiology, and End Results (SEER) population-based study.Data of patients were obtained from the SEER database from 1990 to 2012, and analyzed using Kaplan-Meier survival methods and Cox regression proportional hazard model. The prognostic value of the LNR on cause-specific survival (CSS) and overall survival (OS) were calculated. A total of 5,926 patients were identified. Univariate analysis showed that the number of removed lymph nodes (RLNs), the number of positive lymph nodes, and the LNR were significantly associated with CSS and OS ( P 0.42, the 5-year CSS was 53.1% and 34.7%, respectively ( P < 0.001), and the 5-year OS was 50.4% and 32.0%, respectively ( P < 0.001). The prognostic value of the LNR persisted for patients after stratification by the numbers of RLNs, tumor histology, and tumor grade. LNR is a more accurate prognostic method for stage IIIC EOC patients. Patients with a higher LNR are associated with poorer survival in stage IIIC EOC.