Wen-Wen Zhang

Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3

Introduction Although some circRNAs have been found to regulate the progression of malignancies, their functions and coupled molecular mechanisms are still unclear. In our study, we sought to assess the underlying molecular mechanisms of circRNAs in breast cancer and therefore explored the differentially expressed circRNAs and co-expression networks, followed by in vitro experiments. Materials and methods High-throughput RNA sequencing was performed to obtain an unbiased profile of circRNA expression. CircRNA-miRNA-mRNA co-expression networks were predicted, and sequence analyses were carried out. The MTT, transwell migration and invasion assay was conducted in Michigan Cancer Foundation-7 cells that had been transfected with si-circRNA and si-negative control (si-NC). Results A total of 152 circRNAs were differentially expressed in breast cancer tissues, among which 85 were upregulated and 67 downregulated. Out of these, hsa_circ_0011946 was selected and the subsequent bioinformatics analysis predicted that hsa_circ_0011946 sponging miR-26a/b directly targeted replication factor C subunit 3 (RFC3) and that its knockdown could inhibit RFC3 mRNA and protein expression. Furthermore, hsa_circ_0011946 loss-of-function significantly suppressed the migration and invasion of Michigan Cancer Foundation-7 cells. Conclusion Together, these results indicate that hsa_circ_0011946 and RFC3 comprise a novel pathway involved in the progression of breast cancer.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis:

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer–specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2− and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor−/human epidermal growth factor receptor 2+ and hormone receptor−/human epidermal growth factor receptor 2− subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor−/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer–specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor−/human epidermal growth factor receptor 2− subtype conferred a significantly poorer outcome in terms of breast cancer–specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer–specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer–specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer–specific survival and overall survival.

The Clinicopathological Features and Survival Outcomes of Different Histological Subtypes in Triple-negative Breast Cancer

Purpose: To determine the clinicopathological features and survival outcomes of triple-negative breast cancer (TNBC) according to different histological subtypes. Methods: Using the Surveillance, Epidemiology, and End Results database, we included TNBC cases in 2010-2013. The effect of histological subtype on breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed using univariate and multivariate analyses. Results: A total of 19,900 patients were identified. Infiltrating ductal carcinoma not otherwise specified accounted for 91.6% of patients, followed by metaplastic carcinoma (2.7%), medullary carcinoma (1.4%), mixed lobular-ductal carcinoma (1.4%), lobular carcinoma (1.3%), apocrine carcinoma (1.0%), and adenoid cystic carcinoma (0.6%). Medullary carcinoma was more frequently poorly/undifferentiated. Significantly more lobular carcinoma, mixed lobular-ductal carcinoma, and metaplastic carcinoma patients had larger tumors. Adenoid cystic carcinoma, metaplastic carcinoma, medullary carcinoma, and apocrine carcinoma were more frequently node-negative. Lobular carcinoma (16.0%) and mixed lobular-ductal carcinoma (10.4%) more frequently had distant stage at initial diagnosis. Histologic subtype was an independent prognostic factor of BCSS and OS. Compared with infiltrating ductal carcinoma, medullary carcinoma and apocrine carcinoma had better BCSS and OS, while mixed lobular-ductal carcinoma and metaplastic carcinoma had worse survival. Adenoid cystic carcinoma survival was not significantly different from that of infiltrating ductal carcinoma. Conclusions: TNBC histological subtypes have different clinicopathological characteristics and survival outcomes. Medullary carcinoma and apocrine adenocarcinoma have excellent prognosis; mixed lobular-ductal carcinoma and metaplastic carcinoma are the most aggressive subtypes.

Trends and Outcomes of Sentinel Lymph Node Biopsy in Early-stage Vulvar Squamous Cell Carcinoma: A Population-based Study

Purpose: To compare trends and outcomes between lymphadenectomy and sentinel lymph node biopsy (SLNB) in node-negative early-stage vulvar squamous cell carcinoma (SCC) using a population-based cancer registry. Methods: Patients with vulvar SCC registered on the Surveillance, Epidemiology, and End Results program between 2003 and 2013 were identified. Statistical analysis was performed using Cox regression proportional hazards to calculate hazard ratio (HR) and 95% confidence interval (CI). A 1:1 propensity score matching (PSM) method was performed to minimize selection bias. Results: A total of 1475 patients were identified, including 1346 (91.3%) who received lymphadenectomy and 129 (8.7%) who underwent SLNB. The proportion of patients receiving SLNB increased between 2008 and 2013 compared with the years 2003-2007 (13.9% vs. 3.7%, p < 0.001). Five-year cause-specific survival (CSS) in patients who received lymphadenectomy and SLNB was 91.8% and 92.9%, respectively (p = 0.912), and 5-year overall survival (OS) was 77.5% and 82.5%, respectively (p = 0.403). SLNB was not associated with an decrease in CSS (HR 1.024, 95% CI 0.474-2.213, p = 0.952) or OS (HR 0.874, 95% CI 0.541-1.410, p = 0.581) in univariate and multivariate analyses. A total of 115 pairs were selected by PSM and survival analysis also showed comparable CSS (p = 0.481) and OS (p = 0.545) between lymphadenectomy and SLNB. Conclusions: There is an increasing trend toward SLNB in the treatment of patients with node-negative early-stage vulvar SCC, and survival is comparable between lymphadenectomy and SLNB.

Omission of Postoperative Radiotherapy in Women Aged 65 Years or Older With Tubular Carcinoma of the Breast After Breast-Conserving Surgery

Introduction To investigate the temporal trends of postoperative radiotherapy (RT) administration and the effects of omitting postoperative RT on breast cancer-specific survival (BCSS) in women aged ≥65 years with tubular carcinoma (TC) of the breast who received breast-conserving surgery (BCS). Methods We included women aged ≥65 years with non-metastatic TC of the breast who underwent BCS between 2000 and 2013 using the Surveillance, Epidemiology, and End Results database. Statistical analyses were performed using chi-square tests, Kaplan–Meier analyses, Cox proportional hazards models, and a 1:1 propensity score matching (PSM). Results Before PSM, a total of 1,475 patients with tumor size ≤2 cm, node-negative disease, and estrogen receptor-positive disease were identified, including 927 (62.8%) underwent postoperative RT and 548 (37.2%) had postoperative omission of RT. The administration of postoperative RT steadily declined over the study period. Patients with younger age, larger tumor size, and other race/ethnicity were more likely to receive postoperative RT. The median follow-up duration was 85.0 months, the 5- and 10-year BCSS rates were 98.7 and 97.9%, respectively. The median BCSS was 161.9 and 165.0 months for patients with and without postoperative RT, respectively, and the corresponding 5-year BCSS rates were 98.5 and 98.8%, respectively (p = 0.134). Prognostic analysis indicated that postoperative RT was not associated with improved BCSS rates compared with RT omission (p = 0.134). After PSM, a total of 431 complete pairs were generated. In the matched population, the 5-year BCSS rates were 98.6 and 98.4% in non-postoperative RT and postoperative RT groups, respectively (p = 0.858). The univariate analyses also confirmed that the administration of postoperative RT was not associated with better BCSS (p = 0.858). Conclusion The incidence of breast cancer-related death is probably sufficiently low to avoid postoperative RT in women aged ≥65 years with TC of the breast after BCS.

Survival in signet ring cell carcinoma varies based on primary tumor location: a Surveillance, Epidemiology, and End Results database analysis

ABSTRACT Background: The aim of this study was to investigate the survival of patients with signet ring cell carcinoma (SRCC) based on primary tumor location. Methods: Patient data were obtained from the Surveillance, Epidemiology, and End Results database (1988–2012) with ≥200 cases per tumor location. Cox regression analysis was used to investigate prognostic factors of cause-specific survival (CSS). Results: We identified 24,171 patients. Of the patients, 63.4% had gastric SRCC, followed by colon (18.2%), esophageal (5.0%), rectal (3.5%), lung (3.1%), pancreatic (1.8%), breast (1.5%), bladder (1.3%), small intestine (1.1%), and gallbladder SRCC (1.0%). The 5-year CSS was 22.1%, 69.0%, 33.2%, 28.1%, 24.8%, 16.1%, 13.6%, 12.6%, 11.0%, 6.4% in patients with gastric, breast, colon, rectum, bladder, small intestine, esophageal, gallbladder, lung, and pancreatic SRCC, respectively (P < 0.001). Multivariate analyses showed that the primary tumor location was an independent prognostic factor of survival. Patients with lung, small intestine, and bladder SRCC had a comparable CSS to gastric SRCC, while breast and colorectal SRCC had better survival than gastric SRCC. Esophageal, gallbladder, and pancreatic SRCC were significantly associated with poor CSS compared with gastric SRCC. Conclusion: Our study suggests a major difference in survival of SRCC based on the primary tumor locations.

Comparison of survival outcomes between radical hysterectomy and definitive radiochemotherapy in stage IB1 and IIA1 cervical cancer

Introduction There is an ongoing debate regarding the optimal local treatment modalities for stage IB1 and IIA1 cervical cancer. The aim of this study was to determine whether radical hysterectomy or definitive radiochemotherapy is superior in stage IB1 and IIA1 cervical squamous cell carcinoma (SCC). Methods From 1990 to 2010, a total of 3,769 patients with stage IB1 and IIA1 cervical SCC were included from the Surveillance, Epidemiology, and End Results database and were stratified according to whether they received radical hysterectomy or primary radiochemotherapy. Propensity score-matching (PSM) methods were used to balance patient baseline characteristics. Cancer-specific survival (CSS) and overall survival (OS) were compared between the two groups. Results Of the 3,769 patients, 3,653 (96.9%) and 116 (3.1%) patients received radical hysterectomy and definitive radiochemotherapy, respectively. Radiochemotherapy was rarely used for definitive treatment prior to 2000. Before PSM, patients who were older, of black ethnicity, and with larger tumor size and stage IIA1 disease were more likely to receive definitive radiochemotherapy. A total of 116 pairs were completely matched using PSM. The local treatment modalities had no effect on CSS or OS in either unmatched or matched populations. In the matched population, the 8-year CSS rates were 82.1% and 76.5% in surgery and radiochemotherapy groups, respectively (p=0.382). The 8-year OS rates were 74.6% and 67.8% in surgery and radiochemotherapy groups, respectively (p=0.205). Conclusion Our population-based study suggests that there is no clear local treatment of choice on survival outcomes between radical hysterectomy and definitive radiochemotherapy in patients with stage IB1 and IIA1 cervical SCC.

Survival benefits with the addition of adjuvant hysterectomy to radiochemotherapy for treatment of stage I-II adenocarcinoma of the uterine cervix: HUANG et al.

Background and Objectives: To determine the survival benefits of additional adjuvant hysterectomy in the International Federation of Gynecology and Obstetrics (FIGO) stage I‐II cervical adenocarcinoma patients treated with radiochemotherapy.

The Effect of Marital Status on Nasopharyngeal Carcinoma Survival: A Surveillance, Epidemiology and End Results Study

Purpose: This study examined the role of marital status on survival outcome of nasopharyngeal carcinoma (NPC) patients using a population-based cancer registry. Methods: Patients with primary NPC diagnosed between 2004 and 2013 were included using the Surveillance, Epidemiology and End Results program. Patient demographic, clinicopathologic features, management, and survival outcomes were compared according to marital status. Cause-specific survival (CSS, NPC-related death) for marital status was analyzed. Results: The data of 3018 patients were included, with 61.4%, 11.1%, 21.8, and 5.6% of patients married, divorced (or separated), single, and widowed, respectively. Widowed patients had the highest proportion of elderly age (p < 0.001), were more likely to be female (p < 0.001), and had more well-to-moderately differentiated (p < 0.001) and node-negative disease (p = 0.038). Widowed patients were also less likely to have received radiotherapy and chemotherapy compared with patients of other marital status (p < 0.001). The 5-year CSS was 76.1%, 70.8%, 73.4%, and 59.8% in the married, divorced, single, and widowed groups, respectively (p = 0.001). Marital status was the independent prognostic factor for CSS. Widowed patients had a significantly increased risk of NPC-related death compared with married (hazard ratio [HR] 2.014, 95% confidence interval [CI] 1.477-2.747, p < 0.001), divorced (HR 1.580, 95% CI 1.087-2.295, p = 0.017), and single (HR 2.000, 95% CI 1.402-2.854, p < 0.001) patients. The divorced (p = 0.067) and single (p = 0.949) groups had similar CSS to the married group. Conclusions: Being widowed was associated with an increased the risk of cancer mortality in NPC compared with being married, divorced, or single.

The effect of lymphadenectomy in advanced ovarian cancer according to residual tumor status: A population-based study

BACKGROUND We investigated the effect of lymphadenectomy on the survival outcomes of patients with advanced epithelial ovarian cancer in the Surveillance, Epidemiology, and End Results database according to residual disease status. METHODS We evaluated 3048 patients with International Federation of Gynecology and Obstetrics stage-IIIC-IV epithelial ovarian cancer. We assessed the effect of lymphadenectomy stratified by residual disease size on cause-specific survival (CSS). RESULTS A total of 1904 (62.5%) patients received lymphadenectomy, and 1355 (71.2%) patients had nodal metastases. Lymph-node status had no significant association with residual tumor size in the lymphadenectomy group. In multivariate analysis, lymphadenectomy was associated with a significantly better CSS and was an independent prognostic factor for CSS. Patients with >10 lymph nodes removed had better CSS compared with non-lymphadenectomy and 1-10 lymph nodes removed groups. Lymphadenectomy was associated with a significantly better CSS in patients with no gross residual tumor, but not in patients with residual tumor ≤1 cm or >1 cm. CONCLUSIONS Lymphadenectomy is significantly associated with a better survival outcome in patients advanced ovarian cancer, but its positive effect diminishes as residual tumor size increases.