Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.

Abstract. Multiple studies have reported the prognostic association of certain inflammatory factors with various types of cancer. The present study assessed the prognostic value of the C-reactive protein (CRP)/albumin (Alb) ratio and the neutrophil/lymphocyte ratio (NLR), separately and in combination, in gastric cancer (GC). A total of 337 cases pathologically diagnosed with gastric adenocarcinoma were retrospectively evaluated. The clinicopathological and prognostic relevance of the CRP/Alb ratio and NLR and their combination were analyzed. The optimal cut-off values of the CRP/Alb ratio and NLR were 0.38 and 3.14, respectively. High CRP/Alb ratio (≥0.38) and NLR (≥3.14) values were associated with increased tumor invasion, more distant metastasis and a more advanced tumor-node-metastasis stage (all P<0.05). In addition, a high NLR value was also associated with increased tumor size (P= 0.02). The CRP/Alb ratio (≥0.38/<0.38) and NLR (≥3.14/<3.14) were independent prognostic factors for overall survival time (OS) in GC by multivariate analysis (P= 0.005 and P= 0.001). Using the CRP/Alb ratio and NLR classification, patients were stratified into three subgroups with different OS time (P<0.001), which were identified as independent prognostic variables in multivariate analysis (P<0.001). The present study demonstrated that the CRP/Alb ratio and NLR were independent prognostic factors for OS in patients with GC. The combination of these indexes was associated with significant prognostic value and may further stratify prognosis. IntroductionGastric cancer (GC) is one of the most common types of tumor globally. In 2015, GC had the second highest incidence and rate of mortality among cancer patients in China (1). Due to the rapid progression of GC and the absence of early specific symptoms and signs, the majority of patients are diagnosed at the late stage of gastric carcinoma (2-5). At present, surgery is the preferred treatment for patients without distant metastasis, and postoperative metastasis and recurrence are the predominant causes of mortality (3,5). Although disease-free and overall survival (OS) may be improved by postoperative chemotherapy and radiotherapy, the prognosis of GC remains poor (3,6). Identifying simple but effective prognostic markers for GC remains an important aim for researchers.Inflammation occurs in various types of tumor, and serves a crucial function in tumor development and distant metastasis (7-10). Previous studies have indicated that inflammation is associated with the formation of the tumor microenvironment by inflammatory mediators, including vasoactive amines and cytokines (11-13). The C-reactive protein (CRP)/albumin (Alb) ratio is used as a novel inflammation-based prognostic indicator in multiple types of tumor. Previous studies have demonstrated the prognostic value of CRP/Alb ratio in colorectal (14) and esophageal cancer (15), hepatocellular carcinoma (16), and renal (17) and pancreatic cancer (18). Another important inflammatory marker is the neutrophil/lymphocyte ratio (...

The aim of this study is to establish and validate an effective prognostic nomogram in patients with AFP-negative hepatocellular carcinoma (HCC). The nomogram was based on a primary cohort that consisted of 419 patients with clinicopathologically diagnosed with HCC, all the data was gathered from 2008 to 2014 in Sun Yat-sen University Cancer Center. All the model factors were determined by univariate and multivariate Cox hazard analysis. The concordance index (C-index) and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram, and compared with the TNM staging systems on HCC. Internal validation was assessed. An independent validation cohort contained 150 continuous patients from 2014 to 2015. Independent factors for overall survival (OS) were body mass index (BMI), tumor stage, distant metastases, HBs Ag, lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), and albumin (ALB), which were all contained into the nomogram. The calibration curve for probability of OS showed good agreement between prediction by nomogram and actual observation. The C-index of nomogram was 0.807 (95% CI: 0.770-0.844), which was superior to the C-index of AJCC TNM Stage (0.697). The AUC was 0.809(95%CI: 0.762-0.857). In the validation cohort, the nomogram still gave good discrimination (C-index: 0.866, 95% CI: 00.796-0.936; AUC: 0.832, 95%CI: 0.747-0.917) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively. The proposed nomogram presents more accurate and useful prognostic prediction for patients with AFP-negative HCC.

Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases) and validation group (431 cases). The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039). In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50) also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015). Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer.

Background: Noninvasive prognostic tools for esophageal squamous cell carcinoma (ESCC) are urgently needed. Serum lipids and lipoproteins are used for the prognosis of certain diseases; however, the prognostic value of serum apolipoprotein A-I (ApoA-I) in ESCC has not been described. Methods: Pre-treatment serum lipids and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) were analyzed retrospectively and compared between 210 patients with ESCC and 219 healthy controls. The prognostic significance of serum lipids and lipoproteins was determined by univariate and multivariate Cox hazard models in ESCC. Results: Clinical characteristics (age, sex, pT status, pN status, pM status, pTNM status, histological differentiation or alcohol index) had no influence on baseline ApoA-I level. Serum ApoA-I, HDL-C, LDL-C, and TC levels were significantly lower and Apo-B was significantly higher in ESCC patients than in normal controls. On univariate analysis, ApoA-I, alcohol index, pT status, pN status and pTNM status were associated with significantly poor survival, and ApoA-I (p = 0.039), alcohol index (p = 0.037) and pTNM status (p = 0.000) were identified as prognostic factors associated with shorter survival in the multivariate analysis. Conclusions: Overall survival was shorter in ESCC patients with decreased pre-treatment ApoA-I levels. Our findings suggest that serum ApoA-I level should be evaluated as a predictor of survival in patients with ESCC.

BackgroundAvailable data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5-fluorouracil (TPF) or cisplatin and 5-fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT).MethodsIn total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival, using the propensity score method.ResultsIn total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442–0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411–0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406–0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse-free survival before or after matching.ConclusionsIn our study, IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.

BackgroundThe aim of this study was to propose a prognostic scoring system based on preoperative serum apolipoprotein A-1 and C-reactive protein (ApoA-1 and CRP, AC score) levels and to evaluate the prognostic value of these markers in patients with hepatocellular carcinoma (HCC).MethodsIn all, 539 consecutive cases diagnosed with HCC from 2009 to 2012 at Sun Yat-sen University Cancer Center were analysed. The characteristics and levels of pretreatment lipids (ApoA-1, apolipoprotein B (Apo-B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs)) and CRP were reviewed and determined by univariate and multivariate Cox hazard models. Then, the AC score was proposed, which combines two independent risk factors (ApoA-1 and CRP).ResultsThe optimal cut-off points in our study were determined according to established reference ranges. Patients with decreased ApoA-1 levels (< 1.090 g/L) and increased CRP levels (≥3.00 mg/L) exhibited a significantly poor overall survival (OS) and disease-free survival (DFS). The AC score was calculated as follows: patients with decreased ApoA-1 and elevated CRP were given a score of 3, patients with only one of these abnormalities were given a score of 2, and those with no abnormalities were given a score of 1. Patients with a higher AC score showed more progressive disease and a poorer prognosis. This was observed not only in the entire cohort (for OS, P < 0.001; for DFS, P < 0.001) but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). The discriminatory ability of the AC score in HCC was assessed according to the AUC values. The AUC value of the AC score (AUC: 0.676, 95% CI: 0.629–0.723, P < 0.001) was higher than that of AFP. In addition, the combination of the AFP and AC scores (AUC: 0.700, 95% CI: 0.655–0.745, P < 0.001) was superior to the AFP and AC scores alone.ConclusionsThe AC score is a significant valuable predictor of OS and DFS and could more accurately differentiate the prognosis of HCC patients. As this study is a retrospective analysis, the value of the AC score should be validated in large prospective trials.

BackgroundPatients with HBsAg-positive gastric cancer (GC) are a heterogeneous group, and it is not possible to accurately predict the overall survival (OS) in these patients.MethodsWe developed and validated a nomogram to help improve prediction of OS in patients with HBsAg-positive GC. The nomogram was established by a development cohort (n = 245), and the validation cohort included 84 patients. Factors in the nomogram were identified by univariate and multivariate Cox hazard analysis. We tested the accuracy of the nomograms by discrimination and calibration, and plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context. Then we evaluated the risk in the two cohort.ResultsSignificant predictors were age, tumor stage, distant metastases, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. The nomogram had a concordance index (C-index) of 0.812 (95% CI 0.762–0.862), which was superior than the C-index of AJCC TNM Stage (0.755, 95% CI 0.702–0.808). The calibration plot in the validation cohort based on 5 predictors suggested good agreement between actual and nomogram-predicted OS probabilities. The decision curve showed that the nomogram in predicting OS is better than that of TNM staging system in all range. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and high risk group, respectively.ConclusionThis nomogram, using five pre-treatment characteristics, improves prediction of OS in patients with HBsAg-positive gastric cancer. It represents an improvement in prognostication over the current TNM stage. To generalize the use of this nomogram in other groups, additional validation with data from other institutions is required.