Factor For Poor Overall Survival Research Articles

Prognostic Value of Immune-Related lncRNA SBF2-AS1 in Diffuse Lower-Grade Glioma.

LncRNA SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) has been proven to play an oncogenic role in various types of tumors, but the prognostic role of SBF2-AS1 in tumors, especially in diffuse lower-grade glioma (LGG), is still unclear. Here, we aimed to investigate the prognostic value of SBF2-AS1 in LGG. The LGG expression profiles from The Cancer Genome Atlas (TCGA, n = 524) and Chinese Glioma Genome Atlas (CGGA, n = 431) were mined by Kaplan-Meier analysis, Cox regression analysis, Chi-square test and GSEA analysis. Through Kaplan-Meier analysis, we found the prognosis of LGG patients with high expression of SBF2-AS1 were worse than that of patients with low expression (Log Rank P < 0.001). Cox analysis showed SBF2-AS1 was an independent prognostic factor for poorer overall survival in LGG (P < 0.05). SBF2-AS1 was found to be significantly related to IDH mutation status and SBF2-AS1 was highly expressed in IDH wildtype group. GSEA analysis obtained a total of 126 GO terms and 6 KEGG pathways that were significantly enriched in SBF2-AS1 high expression phenotype (NOM P value < 0.05). We found these 126 GO terms and KEGG pathways were mainly related to immunity. In conclusion, lncRNA SBF2-AS1 expression is an immune-related lncRNA associated with unfavorable overall survival in LGG. SBF2-AS1 could be a reliable prognostic biomarker for patients with LGG.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim:Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

A new prognosis prediction model combining TNM stage with MAP2K4 and JNK in postoperative pancreatic cancer patients

Mitogen-activated protein kinase kinase 4 (MAP2K4) is a tumor suppressor in many cancers. However, its roles and action mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we analyzed MAP2K4 and its downstream kinases (c-Jun N-terminal kinase (JNK) and p38) using immunohistochemical staining and their prognostic significances using univariate and multivariate Cox proportional hazards regression analysis in our PDAC cohort. Then, we validated MAP2K4/JNK/p38 mRNA levels and prognostic significances using The Cancer Genome Atlas (TCGA) database. Finally, we evaluated the effects of MAP2K4 on the proliferation and invasion of PDAC cells. MAP2K4, JNK, and p38 proteins were expressed in 97.3 % (72/74), 95.6 % (65/68), and 88.6 % (62/70) of the samples, respectively, and their levels in tumor tissues were significantly higher than those in normal ducts. MAP2K4 protein expression was lower in male patients (p = 0.028). In our PDAC cohort, advanced TNM stage, low MAP2K4, and high JNK protein levels were significant prognostic factors for poor overall survival (OS) based on a univariate survival analysis (p = 0.006, p < 0.001, and p = 0.004, respectively). N stage and MAP2K4 and JNK protein levels were independent prognostic factors for OS based on multivariate analysis. We then built a prognosis prediction nomogram combining the standard TNM staging system with MAP2K4 and JNK expression that had a Harrell’s C-index of 0.645. The new prognosis prediction model effectively stratified the resected patients with PDAC, from both our cohort and TCGA database, into low- and high-risk groups. Finally, MAP2K4 overexpression inhibited pancreatic cancer cell proliferation and migration in vitro. This study shows that reduced protein and mRNA levels of MAP2K4 found in PDAC patients, coupled to in vitro effects observed, support the tumor suppressor role of MAP2K4 in PDAC. Importantly, combining MAP2K4 and JNK expression with the TNM staging system results in a better prediction of postoperative survival of patients with PDAC.

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer.

BACKGROUNDProgrammed death ligand 1 (PD-L1) immunotherapy remains poorly efficacious in colorectal cancer (CRC). The recepteur d’origine nantais (RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.AIMTo identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.METHODSGene expression data from the Gene Expression Omnibus database (GEO; n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM; n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot.RESULTSIn the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121 (32%), 43 (11%), 91 (24%), and 51 (13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment (P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells.CONCLUSIONRON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.

Long-Term Outcomes and Prognostic Factors of Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged ≥75 Years.

Simple SummaryThe number of elderly patients with early gastric cancer (EGC) who meet the indications for endoscopic submucosal dissection (ESD) is increasing. Since elderly patients have more comorbidities, and lower life expectancy than younger patients, special considerations to establish treatment strategies according to prognosis is needed. We investigate overall survival and risk factors related to survival after ESD in these patients. During the follow-up, the 3-, 5-, and 10-year overall survival was 91.2%, 83.5%, and 54.5%, respectively. Smoking, history of cancer of other organs, neutrophil to lymphocyte ratio > 1.6, Charlson comorbidity index ≥ 3, and presence of lymphovascular invasion were independent five risk factors for poor overall survival. The long-term outcome of ESD was poorer in elderly patients with risk factors than in those without. These prognostic factors can also be useful in deciding whether to recommend additive surgery and a close follow-up after non-curative endoscopic treatment in the elderly patients.Background and Aims: The number of elderly patients with early gastric cancer (EGC) who meet the indications for endoscopic submucosal dissection (ESD) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing ESD for EGC. Methods: Between January 2006 and December 2018, 439 patients aged ≥75 years who underwent ESD for EGC were analyzed. The clinical outcomes and prognosis were evaluated, and independent risk factors for OS were identified. Results: The mean patient (302 men, 137 women) age was 78.3 (range 75–92) years. En bloc, R0, and curative resections were achieved in 96.8%, 90.7%, and 75.6%, respectively, without severe adverse events. During the follow-up (median 54.2 (range 4.0–159.6) months), 86 patients died (three of gastric cancer). The 3-, 5-, and 10-year OS was 91.2%, 83.5%, and 54.5%, respectively, and the 3-, 5-, and 10-year cancer related survival rate were 99.7%, 99.1% and 97.5%, respectively. In multivariate analysis, smoking, history of cancer of other organs, NLR > 1.6, Charlson comorbidity index ≥ 3, and presence of lymphovascular invasion (hazard ratio = 3.96, 1.78, 1.83, 1.83, and 2.63, respectively, all p < 0.05) were independent five risk factors for poor OS. The high-risk group (≥3 risk factors) showed a significantly lower OS than the low-risk group (<2 risk factors) (p < 0.001). Conclusions: The five factors could be useful in predicting the long-term prognosis of elderly ESD patients or deciding the therapeutic approaches in case of non-curative resection.

Long-term outcomes of patients undergoing hepatectomy for bilateral multiple colorectal liver metastases-a propensity score matching analysis

Objective: Liver is the most common site of distant metastasis in colorectal cancer patients. Currently, surgical resection of colorectal liver metastasis (CRLM) still remains the most curative therapeutic option which is associated with long-term survival. However, the outcome of CRLM patients with bilobar multiple lesions has been reported to be extremely poor due to the complex techniques of the surgery and the difficulties to achieve a negative resection margin. In this study, postoperative long-term outcome in patients with bilobar versus unilobar multiple CRLM undergoing surgical resection were compared and the prognostic factors of CRLM were analyzed. Methods: A retrospective cohort study was performed. The clinicopathological data were collected retrospectively from patients with multiple CRLM who received liver resection between January 2002 and November 2018 at our department. Inclusion criteria: (1) All CRLM lesions were confirmed by preoperative enhanced CT or MRI and enhanced ultrasonography. (2) All CRLM lesions were resectable either initially or converted by systemic treatments. The CRLM patients were considered as resectable, if their extrahepatic diseases were able to be completely removed. (3) Sufficient remnant liver volume was required to maintain normal liver function, which was defined by the ratio of remnant liver volume to total liver volume (RLV-TLV), of greater than 30% in general or 40% for the patients undergoing chemotherapy. (4) Medical records and follow-up information were intact. Those undergoing multiple operations after recurrence, with R2 resection, or with a single CRLM lesion were excluded. Patients were divided into bilobar and unilobar group according to tumor distribution. One-to-one propensity score matching (PSM) was performed to balance the covariates between the bilobar group and unilobar group. After PSM, the differences in long-term outcomes between the two groups were compared. Results: A total of 491 patients met the inclusion criteria, 344 (69.6%) with bilobar and 147 (30.4%) with unilobar CRLM. In the propensity-score-matched population (bilobar, 143; unilobar, 143), baseline characteristics were similar between the two groups. The 1-, 3-, and 5-year overall survival rates in the bilobar group were 91.6%, 52.1%, and 35.3% respectively, compared with 93.7%, 56.8%, and 43.8% in the unilobar group, and the difference was not statistically significant (P=0.204). The 1-, 3-, and 5-year recurrence-free survival rates in the bilobar group were 45.7%, 33.7%, and 33.7% respectively, compared with 62.5%, 44.1%, and 42.1% in the unilobar group, and the difference was not statistically significant (P=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, P=0.543). Univariate analysis showed that N stage of primary tumor, diameter of the largest liver metastases, carcinoembyonic antigen level, RAS gene status and clinical risk score (CRS) were significantly associated with the prognosis of CRLM (all P<0.05). Multivariate analysis indicated that diameter of largest liver metastases > 5 cm (HR=1.888, 95% CI: 1.251-2.848, P=0.002), CRS≥3 (HR=1.552,95% CI:1.050-2.294, P=0.027) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, P=0.012) were independent risk factors of poor overall survival after hepatectomy. Conclusions: Tumor distribution may not affect the prognosis of multiple CRLM after resection. Surgical removal in patients with bilobar multiple CRLM provides comparable long-term survival to unilobar multiple CRLM.

Preoperative low hematocrit is an adverse prognostic biomarker in ovarian cancer.

The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan-Meier method and log-rank test. 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050-2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7months in patients with preoperative HCT ≥ 35% and 61.7months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65years, BMI ≥ 25.0kg/m2, ascites volume ≤ 500mL, ASA score < 3, albumin ≥ 35g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110g/mL), low albumin (< 35g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. Preoperative low HCT was a valuable predictor for EOC patients' poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.

Efficacy of the physiobiological parameter-based grading system for predicting the long-term prognosis after curative surgery for resectable pancreatic cancer

BackgroundSeveral prognostic scoring systems based on cancer-related inflammation have been developed. We aimed to evaluate the efficacy of a novel physiobiological parameter-based grading system (PGS) for predicting the long-term prognosis after curative-intent surgery for pancreatic ductal adenocarcinoma. MethodsOne-hundred fifty-nine consecutive patients with pancreatic ductal adenocarcinoma were enrolled. Univariate and multivariate analyses were performed to identify variables associated with overall survival and recurrence-free survival. Patients were stratified according to the PGS score with a cut-off value of 40.5 being estimated by receiver-operating characteristic curve analysis. Propensity score matching analysis (PSM) was performed to compare between patients with low and high scores in the physiobiological parameter-based grading system. ResultsUnivariate analysis showed that CEA elevation (p = 0.032), tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), Prognostic nutritious index (PNI) ≤40 (p = 0.002) and positive Glasgow prognostic score (GPS) (p = 0.001) were risk factors for poor overall survival. CEA elevation (p = 0.006), Tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), PNI ≤40 (p = 0.017) and positive GPS (p < 0.001) were identified as risk factors for poor recurrence-free survival. The multivariate analysis revealed that tumor size ≥20 mm (p = 0.007, p = 0.008, respectively) and high PGS score (p = 0.041, p = 0.018, respectively) were independently associated with poor overall survival and recurrence-free survival. Patients with high-PGS showed a significantly worse long-term prognosis even after PSM. ConclusionThe PGS is a novel nomogram that could effectively predict long-term outcomes following curative surgery in patients with pancreatic ductal adenocarcinoma.

Prediction of the prognosis of advanced hepatocellular carcinoma by TERT promoter mutations in circulating tumor DNA.

Human telomerase reverse transcriptase (TERT) promoter mutations were the most prevalent mutations in patients with hepatocellular carcinoma (HCC). We tried to detect the mutations with plasma circulating tumor DNA (ctDNA) in patients with advanced HCC and elucidated their clinical utility. Circulating tumor DNA in plasma was extracted from 130 patients with advanced HCC who were treated with systemic chemotherapy (n=86) or transcatheter arterial chemoembolization (n=44), and TERT promoter mutations were examined with digital droplet polymerase chain reaction. The correlations between these mutations and the clinical outcome of patients were analyzed. Of the 130 patients examined, 71 patients (54.6%) were positive for TERT promoter mutations in ctDNA, of which 64 patients were -124bp G>A and 10 were -146bp G>A. The presence of TERT promoter mutations was correlated with large intrahepatic tumor size (P=0.05) and high des-gamma carboxyprothrombin (P=0.005). Overall survival of the patients with the mutations was significantly shorter than those without them (P<0.001), and the patients with high (≥1%) fractional abundance of the mutant alleles showed shorter survival than those with low (<1%) fractional abundance. Multivariate analysis revealed that TERT promoter mutation (hazard ratio [HR]: 1.94; 95% confidence interval [CI], 1.18-3.24; P<0.01), systemic chemotherapy (HR: 2.38; 95% CI, 1.29-4.57; P<0.01), and vascular invasion (HR: 2.16; 95% CI, 1.22-3.76; P<0.01) were significant factors for poor overall survival. TERT promoter mutations in ctDNA were associated with short survival and could be a valuable biomarker for predicting the prognosis of patients with advanced HCC.

Circular RNA circ-MTO1 serves as a novel potential diagnostic and prognostic biomarker for gallbladder cancer.

Primary gallbladder carcinoma (GBC) is one of the most common biliary malignancies in the gastrointestinal tract. In this work, we examined the roles of circular-mitochondrial translation optimization 1 (circ-MTO1) in GBC tissues and patient plasma. Circ-MTO1 expression in GBC tissues and patient plasma was evaluated by quantitative Real Time-PCR (qRT-PCR). The relationships between circ-MTO1 expression and the pathological characteristics of GBC were analyzed. Kaplan-Meier survival curve was applied to calculate overall survival (OS) and progression-free survival (PFS) in GBC patients with different circ-MTO1 expression. The univariate COX regression curve analysis method was employed to analyze the potential relationships between high circ-MTO1 expression and OS and PFS. At last, we assessed the diagnostic value of the circ-MTO1 level in GBC patient plasma. Circ-MTO1 expression was significantly upregulated in tumor tissues and plasma in GBC patients. In addition, circ-MTO1 expression was associated with clinical-pathological characteristics in GBC. High circ-MTO1 expression served as an independent prognostic factor for poor OS and PFS in GBC patients. Moreover, upregulated plasma circ-MTO1 level was significantly associated with tumor development. Circ-MTO1 is a potential early diagnostic and prognostic biomarker for patients with gallbladder cancer. Thus, our present work might provide a new understanding of the diagnosis and treatment of GBC.

Surgery versus stereotactic body radiotherapy for clinical stage I non-small-cell lung cancer: propensity score-matching analysis including the ratio of ground glass nodules.

To investigate whether surgery and stereotactic body radiotherapy (SBRT) yield comparable outcomes for clinical stage (c-stage) I non-small-cell lung cancer (NSCLC), propensity score-matching (PSM) analysis was conducted. This single-institutional retrospective study included patients who underwent surgery (n = 574) or SBRT (n = 182) between 2004 and 2014. PSM was performed based on tumor diameter, age, sex, performance status, forced expiratory volume, Charlson comorbidity index, and ground glass nodules (GGN) defined as cTis or cT1mi according to the 8th TNM classification. The median follow-up durations for the surgery and SBRT groups were 66 and 69months, respectively. The multivariate analysis revealed that non-GGN was a significant factor for poorer overall survival (OS) and disease-free survival (DFS): hazard ratio (HR) 19.95% confidence interval (CI) 4.7-79, P < 0.001; and HR 28, 95% CI 6.9-110, P < 0.001, respectively. PSM identified 120 patients from each group. The 5-year OS and DFS rates of the surgery vs SBRT groups were 71% (95% CI 61-79) vs 64% (95% CI 54-72) (P = 0.41) and 63% (95% CI 53-72) vs 55% (95% CI 45-63) (P = 0.23) after PSM, respectively. The PSM analyses including the ratio of GGN demonstrated that the OS and DFS for patients with c-stage I NSCLC in the surgery group were slightly superior to those for those in the SBRT group, although both survivals were not significantly different between the two therapeutic approaches.

Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia

The mutational spectrum and prognostic factors of NRAS-mutated (NRASmut) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRASmut AML (13%). Of the 152 NRASmut AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRASmut AML.

The Impact of Severe Infectious Complications on Long-term Prognosis for Gastric Cancer.

The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer. Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses. A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001). Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer.

Controlling Nutritional Status score is superior to Prognostic Nutritional Index score in predicting survival and complications in pancreatic ductal adenocarcinoma: a Chinese propensity score matching study.

Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients' nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.

Muscle impairment during follow-up as an independent prognostic factor for poor overall survival in pancreatic cancer.

e16726 Background: We aimed to assess that muscle impairment during follow-up is as an independent prognostic factor for poor overall survival in pancreatic cancer (PC) and is more accurate than a single muscle mass evaluation. Methods: Data from all patients with pancreatic adenocarcinoma at our center from 2009 to 2015 were retrieved (N = 114). A retrospective review of the total psoas area (TPA) was performed using manual segmentation on a single cross-sectional image through the third lumbar vertebrae for each available scan (N = 713, median number of scans per patient was 6 [3; 8]). For each patient, when at least two CT scans were available, the decrease in the TPA from baseline (Muscle Impairment) was expressed by a percentage. Results: In the univariate analysis, a TPA level under 420 mm2/m2 during the follow-up, with a HR = 3.419 ([2.168; 5.394]; 95% CI; p &lt; 0.0001) and a TPA decrease of more than 20% from the baseline with a HR = 7.169 ([4.526; 11.353]; 95% CI; p &lt; 0.0001) were prognostic factors for death. The multivariate analysis confirmed the results with a HR = 5.799 ([3.418; 9.839]; 95% CI; p &lt; 0.0001) in the non-surgery group and a HR = 8.089 ([2.157; 30.339]; 95% CI; p = 0.0019) in the surgery group for a decrease in the TPA of more than 20% from the baseline. Conclusions: Muscle impairment during follow-up is a strong and independent prognostic factor for poor overall survival in patients with PC. It is in favor of a higher risk of death.

Prognostic Role of Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Level in Early Stage Hepatocellular Carcinoma

The purpose of this study is to evaluate the prognostic value of preoperative Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) in predicting overall survival for patients with hepatitis B- and hepatitis C-related early-stage hepatocellular carcinoma (ESHCC) after liver resection. Post-operative survival rates were compared according to WFA+-M2BP level and tumor stage. Six hundred and ten patients were identified and 198 were removed after application of the exclusion criteria; the median follow-up time was 4.33 years, and cancer-related death occurred in 117 (28.4%) patients. Age (p = 0.03), fibrosis grade (p = 0.042), cancer stage (p = 0.01), and WFA+-M2BP level (p = 0.001) were identified as independent risk factors for poor overall survival. The overall survival rates at 3 and 5 years for patients with WFA+-M2BP ≤ 1.12 were 0.92 and 0.90, respectively, and 0.76 and 0.61 for patients with WFA+-M2BP > 1.12 (p < 0.001). During the analysis of survival prediction, serum WFA+-M2BP level exhibited a higher log-likelihood and a lower AIC value compared to TNM stage (log likelihood: −638; AIC: 1279). Pre-operative serum WFA+-M2BP level provided important prognostic information after curative hepatic resection in our study.

Outcomes analysis of pre-brachytherapy MRI in patients with locally advanced cervical cancer

IntroductionVarious brachytherapy options are available for treating cervical cancer. This study investigated whether pre-brachytherapy magnetic resonance imaging (MRI) findings could help identify the appropriate brachytherapy technique for cervical cancer.MethodsWe retrospectively...

Decreased plasma riboflavin is associated with poor prognosis, invasion, and metastasis in esophageal squamous cell carcinoma.

Riboflavin deficiency confers a predisposition for esophageal cancer. The role of plasma riboflavin levels in development and prognosis of individuals with digestive tract inflammation and ulcer (DTIU), digestive tract polyps (DTPs), and ESCC is not well understood. We performed a cross-sectional study, including 177 DTIU, 80 DTP, and 324 ESCC cases, to measure the plasma riboflavin levels among the three populations. Correlation between plasma riboflavin levels (categorized as ≥31.8, 6.5-31.8 and ≤6.5 nmol/L groups) and clinical characteristics, as well as survival of ESCC patients (556 cases) was analyzed. There was no difference in plasma riboflavin levels between DTIU, DTP, and ESCC cases (P > 0.05). Plasma riboflavin levels were inversely correlated with invasive depth (correlation coefficient = -0.09, P = 0.026) and lymph node metastasis (correlation coefficient = -0.11, P = 0.010) of ESCC, and ESCC patients with low riboflavin levels had poor recurrence-free survival (P = 0.035) and overall survival (P = 0.003). Decreased riboflavin was a prognostic factor for poor overall survival (HR = 1.91, 95% CI = 1.19-3.07, P = 0.007). Plasma riboflavin levels in DTIU, DTP, and ESCC patients are similar. Plasma riboflavin levels are associated with the development and prognosis of ESCC.

Gamma-synuclein as a potential novel prognostic marker promoting tumor cell migration in biliary tract carcinoma.

577 Background: Biliary tract carcinoma (BTC) is a highly malignant tumor, but the detailed pathological mechanism of its development and progression remain ill-defined. Gamma-synuclein (SNCG) promotes invasive behavior in pancreatic cancer and a range of other cancers, and SNCG expression is reportedly a prognostic factor. However, the role of SNCG in BTC remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Methods: Using surgically resected BTC specimens from 149 patients with adenocarcinoma [extrahepatic cholangiocarcinoma (ECC) (n =98); intrahepatic cholangiocarcinoma (ICC) (n =51)], we immunohistochemically evaluated SNCG positivity and checked for correlations with clinicopathological factors and outcomes. Furthermore, cell lines with high expressions of SNCG were selected from 17 BTC cell lines by using immunohistochemistry and qPCR. Cell proliferation and migration assays were then performed in the presence and absence of SNCG (silenced using). Results: SNCG expression was found in 32 of 149 (21.4%) BTC patients. SNCG expression was significantly correlated with poorly differentiated tumor ( P = 0.001) and lymph node metastases ( P = 0.001). SNCG positivity was also correlated with poorly differentiated tumor in both ECC and ICC ( P = 0.008 and P = 0.03, respectively), but was correlated with lymph node metastases only in ECC ( P = 0.003). Multivariate analyses identified SNCG expression as an independent prognostic factor of poor overall survival ( P = 0.008) and poor recurrence-free survival (RFS) ( P = 0.006). SNCG expression in both ECC and ICC was significantly associated with poor prognosis in univariate analysis, and multivariate analysis identified SNCG as an independent prognostic factor of poor RFS for ECC (P = 0.03). High SNCG expression was found in 3 BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing by siRNA suppressed cell migration significantly in NCC-BD1 and NCC-CC6-1 and downregulated cell proliferation in NCC-CC6-1. Conclusions: Our results suggest that SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.

C1GALT1 is associated with poor survival and promotes soluble Ephrin A1-mediated cell migration through activation of EPHA2 in gastric cancer

C1GALT1 controls the crucial step of GalNAc-type O-glycosylation and is associated with both physiologic and pathologic conditions, including cancers. EPH receptors comprise the largest family of receptor tyrosine kinases (RTKs) and modulate a diverse range of developmental processes and human diseases. However, the role of C1GALT1 in the signaling of EPH receptors remains largely overlooked. Here, we showed that C1GALT1 high expression in gastric adenocarcinomas correlated with adverse clinicopathologic features and is an independent prognostic factor for poor overall survival. Silencing or loss of C1GALT1 inhibited cell viability, migration, invasion, tumor growth and metastasis, as well as increased apoptosis and cytotoxicity of 5-fluorouracil in AGS and MKN45 cells. Phospho-RTK array and western blot analysis showed that C1GALT1 depletion suppressed tyrosine phosphorylation of EPHA2 induced by soluble Ephrin A1-Fc. O-glycans on EPHA2 were modified by C1GALT1 and both S277A and T429A mutants, which are O-glycosites on EPHA2, dramatically enhanced phosphorylation of Y588, suggesting that not only overall O-glycan structures but also site-specific O-glycosylation can regulate EPHA2 activity. Furthermore, depletion of C1GALT1 decreased Ephrin A1-Fc induced migration and reduced Ephrin A1 binding to cell surfaces. The effects of C1GALT1 knockdown or knockout on cell invasiveness in vitro and in vivo were phenocopied by EPHA2 knockdown in gastric cancer cells. These results suggest that C1GALT1 promotes phosphorylation of EPHA2 and enhances soluble Ephrin A1-mediated migration primarily by modifying EPHA2 O-glycosylation. Our study highlights the importance of GalNAc-type O-glycosylation in EPH receptor-regulated diseases and identifies C1GALT1 as a potential therapeutic target for gastric cancer.