Neoadjuvant Chemoradiotherapy Does Not Contribute to Worse Survival in Pathological Node-Negative Rectal Cancer.

Purpose: The prognostic significance of ypN0 rectal cancer with comparison to pN0 disease still remains poorly defined. This study aimed to compare the prognosis of ypN0 and pN0 rectal cancer. Methods: Eligible patients were identified from the SEER18 registries research database (the latest data up to date was on April 15, 2019). Propensity score (PS) matching was usually performed to reduce the imbalance and potential confounding that were introduced by inherent differences between the groups. The cause-specific survival (CSS) was analyzed to evaluate the prognostic prediction of ypN0 and pN0 groups using the Kaplan-Meier method with the log-rank test. Cox proportional hazard model was also used to identify independent prognostic variables. Results: In total, 26,832 patients diagnosed with pN0 or ypN0 rectal cancer were confirmed as the final cohort, including 7,237 (27.0%) patients with radiation and 19,595 (73.0%) patients without radiation prior to surgery. The median follow-up time was up to 81 months. After adjusting for other prognostic factors, neoadjuvant radiotherapy was not an independent prognostic variable of CSS (HR = 1.100, 95%CI = 0.957-1.265, P = 0.180, using pN0 group as the reference). Conclusions: ypN0 rectal cancer was strongly associated with worse pathological diagnoses compared with pN0 rectal cancer, contributing to worse oncologic outcomes. However, the receipt of neoadjuvant chemoradiotherapy was not an independent prognostic factor of worse prognosis in pathological node-negative patients. Our study could give guidance to the treatment of ypN0 rectal cancer.

Hsa_circ_0000515 is a novel circular RNA implicated in the development of breast cancer through its regulation of the microRNA-296-5p/CXCL10 axis.

Cancer metastasis is a major cause of death among women afflicted with breast cancer (BC) and understanding the molecular processes involved is a major focus in BC research. Circular RNAs (circRNAs) have emerged as genomic regulatory molecules in carcinogenesis and metastasis; however, their role in BC is unclear. We characterized a novel circRNA, hsa_circ_0000515, in context of BC. We collected 340 cancerous tissues surgically resected from BC patients and found hsa_circ_0000515 was upregulated in BC tissues and associated with poor prognosis of BC. Silencing of hsa_circ_0000515 impaired cell cycle progression, cell proliferation, and invasion, attenuated inflammatory response, and reduced the proangiogenetic potential of BC cells. RNA pull-down and dual-luciferase reporter gene assays showed that hsa_circ_0000515 binds miR-296-5p, preventing it from repressing CXCL10 expression. We also observed that miR-296-5p inhibition or CXCL10 overexpression promoted cell cycle progression, restored proliferative, invasive and proangiogenetic abilities, and increased inflammatory response in MCF-7 cells in the absence of hsa_circ_0000515. In vivo analyses showed that partial loss of hsa_circ_0000515 reduced the tumor growth of MCF-7 cells in nude mice. The key findings from this study revealed that targeting hsa_circ_0000515 might be an effective strategy to combat BC.

Re-Evaluation of the Survival Paradox Between Stage IIB/IIC and Stage IIIA Colon Cancer.

OBJECTIVE: We conducted this large population-based study to re-evaluate the survival paradox between stage IIB/C and stage IIIA colon cancer based on the newest staging criteria. METHODS: Colon cancer patients were recruited from the Surveillance, Epidemiology, and End Results (SEER) database using SEER*Stat software (version 8.3.4) with strict inclusion criteria. We used Chi-square test to compare categorical variables between patients diagnosed with stage IIB/IIC and stage IIIA colon cancer. Survival probabilities were then assessed using the Kaplan-Meier method. Cox proportional hazards models were used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) of clinicopathologic characteristics in stage IIB/IIC and stage IIIA colon cancer patients. RESULTS: In the current study, a total of 9,227 eligible colon cancer patients were collected from the SEER database between 2010 and 2015. It was found that stage IIIA had 66.4% decreased risk of colon cancer-specific mortality compared with stage IIB (HR = 0.336, 95%CI = 0.286-0.394 for stage IIIA, P < 0.001, using stage IIB as the reference) after the adjustment for other known prognostic factors. And T1N2a colon cancer had significantly lower 5-year overall survival (OS) rate compared with T2N1 disease (74.7% vs. 57.1%, P = 0.018). CONCLUSIONS: Our study confirmed the existence of survival paradox between stage IIB/IIC and stage IIIA colon cancer based on the newest staging criteria. What is more, the subgroup analyses revealed that T1N2a had the least influence on the survival paradox. N2a colon cancer seemed to be associated with worse prognosis than T2 disease, which would give us a better understanding of tumor biology of colon cancer and be conducive to the refinement of individualized treatment regimens in stage III disease.

Efficacy of Primary Tumor Resection in Metastatic Colorectal Cancer.

BACKGROUND The aim of this study was to evaluate the survival benefit of palliative primary tumor resection in colorectal cancer (CRC) patients with unresectable metastases. MATERIAL AND METHODS Clinicopathological characteristics of eligible patients who underwent surgery to remove the primary tumor and those who did not between 2004 and 2013 were compared. We also evaluated the association between survival and different clinicopathologic characteristics in metastatic CRC. RESULTS The percentage of patients undergoing surgical resection of the primary tumor was higher during the earlier years and trended toward less use of surgery in later years. Palliative primary tumor resection was strongly associated with better cause-specific survival (hazard ratio=0.403, 95% confidence interval=0.389 to 0.417, P<0.001). CONCLUSIONS We added new strong evidence supporting the survival benefit of palliative resection, which should be confirmed in future randomized controlled trials.

Mucinous Histology Might Be an Indicator for Enhanced Survival Benefit of Chemotherapy in Stage II Colon Cancer.

Background: It was a difficult question to identify candidates who would benefit most from adjuvant chemotherapy in stage II colon cancer because of the paucity of relevant conclusive clinical trial results. We aimed to assess if mucinous adenocarcinoma (MUA) could be an indicator for the efficacy of adjuvant chemotherapy in stage II colon cancer. Methods:Using SEER*Stat software V.8.3.5, eligible patients were then recruited from the SEER database. A χ2 test was applied to compare the distribution of different categorical variables between nonmucinous adenocarcinoma (NMUA) and MUA groups. We then used the Kaplan-Meier method to analyze overall survival (OS) of different histological types in stage II colon cancer, and the log-rank test was then used to assess the OS differences. The Cox proportional regression risk models were also built in our analyses to eliminate potential crossed bias from other prognostic factors. Results:A total of 50,065 patients diagnosed with stage II colon cancer were recruited from the SEER database from 2004 to 2011; all the patients were divided into two groups, including NMUA (n = 44,785) and MUA (n = 5,280). The Cox analysis of the histological type indicated that the survival difference between MUA and NMUA failed to reach statistical significance in stage II colon cancer (P = 0.360). In NMUA, patients treated with adjuvant chemotherapy were independently associated with 37.2% decreased risk of overall mortality compared with those not [hazard ratio (HR) = 0.628, 95% confidence interval (CI) = 0.601-1.656, P < 0.001]; in MUA, the number increased to 41.5% (HR = 0.585, 95% CI = 0.515-0.665, P < 0.001). Conclusions:Our study showed that the survival difference between MUA and NMUA failed to reach statistical significance in stage II colon cancer. More importantly, our study had provided the first evidence that chemotherapy would offer higher survival improvement in MUA compared with NMUA in stage II colon cancer; mucinous histology might be an indicator for enhanced survival benefit of chemotherapy in stage II colon cancer.

The survival benefit of adjuvant radiotherapy for pathological T4N2M0 colon cancer in the Modern Chemotherapy Era: evidence from the SEER database 2004-2015.

Neoadjuvant chemoradiotherapy has been established as the standard treatment for patients with locally advanced rectal cancer. However, the role of radiotherapy (RT) has not been fully confirmed in advanced colon cancer (LACC). We postulated that patients with pathological T4N2 locally advanced colon cancer would benefit more from RT. 6715 pT4N2M0 colon cancer patients were included in the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoints were 5-year overall survival (OS) and cancer-specific survival (CSS). Propensity score matching (PSM) with Kaplan-Meier and Cox proportional hazards' models was performed to estimate prognosis. Before PSM, patients underwent RT had better OS and CSS as compared to patients did not receive RT (OS: 40.1% vs 27.6%, p < .001; CSS: 49.6% vs 41.1%, p = .002). After PSM, 239 matched pairs were formed for further analysis. RT group also presented significantly improved prognosis (OS: 40.1% vs 25.7%, p = .008; CSS: 49.6% vs 38.2%, p = .042). Multivariable Cox regression analysis showed that RT was a protective factor [OS：Hazard ratio (HR) =0.677, 95% Confidence interval (CI): 0.532-0.862, p = .002; CSS: HR = 0.708, 95% CI: 0.533-0.941, p = .018]. For pT4N2M0 colon cancer patients, the addition of RT seems to confer survival benefit as compared to patients who did not receive RT.

EMT induced by loss of LKB1 promotes migration and invasion of liver cancer cells through ZEB1-induced YAP signaling.

Liver cancer cells often exhibit mesenchymal phenotypes, a critical phenotypic alteration of cancer cells termed the epithelial-mesenchymal transition (EMT). To examine whether liver kinase B1 (LKB1) serves a potential role in EMT in liver carcinogenesis, in the present study, it was determined that the expression of LKB1 decreased in the hepatocellular carcinoma (HCC) cell line, compared with a normal liver cell line. LKB1 overexpression decreased cell motility and invasiveness. Furthermore, the loss of LKB1 induced the expression of several EMT marker proteins, including that of Zinc Finger E-Box Binding Homeobox 1 (ZEB1). Notably, the expression of Yes-associated protein (YAP) was positively associated with that of ZEB1 in LKB1-knockdown cells with a mesenchymal phenotype. Here, we describe the direct regulation of the Hippo pathway effector YAP by ZEB1. The findings of the present study demonstrate that ZEB1 regulates the expression of YAP and regulates the expression of downstream target genes to promote malignant progression.