Prognosis Factors For Overall Survival Research Articles

Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Short- and long-term outcomes of robotic versus open radical antegrade modular pancreatosplenectomy: a retrospective propensity score-matched cohort study.

Robotic distal pancreatectomy has increasingly been accepted as it has overcome some of the limitations of open distal pancreatectomy, whilst the outcomes following robotic radical antegrade modular pancreatosplenectomy (RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of robotic RAMPS and open RAMPS for PDAC. The patients who underwent robotic RAMPS and open RAMPS for PDAC at our clinical centre between January 2017 and December 2021 were reviewed. After a propensity score matching (PSM) at a 1:1 ratio, the perioperative and pathological outcomes in the both groups were reviewed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. 318 cases were recorded in robotic and open groups. The robotic group showed advantages in operative time [205.00 (166.00, 240.00) min vs 235 (184.75, 270.00) min, P = 0.002], estimated blood loss [100 (50, 100) ml vs 300 (100, 400) ml, P < 0.001], delayed gastric emptying [0 vs 5.03%, P = 0.007] and postoperative hospital stay [7.00 (5.00, 10.00) days vs 11.00 (8.00, 14.00) days, P < 0.001]. There were no significant differences in rate of severe postoperative complications between the robotic group and the open group. Multivariable analysis showed that carbohydrate antigen 19-9, estimated blood loss, N stage, tumour differentiation, chemotherapy and vascular invasion were independent risk factors for OS and RFS of these patients. Robotic RAMPS was safe and had some advantages over open RAMPS for PDAC. There were no significantly differences in oncological outcomes and long-term survival rates between the robotic and open groups. Robotic RAMPS expanded the indications for minimally invasive surgeries for PDAC to a certain extent.

LENT Score as a Prognosis Factor for Overall Survival and Progression-Free Survival in Malignant Pleural Effusion Patients at Tertiary Hospitals in West Sumatera, Indonesia

Background: Malignant pleural effusion (MPE) has a variable survival rate and prognosis. The LENT score is one method for assessing survival rates in patients with MPE. This study aimed to investigate the LENT score as a prognostic factor for overall survival (OS) and progression-free survival (PFS) of patients with MPE at a tertiary hospital in West Sumatera.&#x0D; Methods: This study was an observational analytic study involving several tertiary hospitals in West Sumatera with a minimum observation period of 2 years. Data were collected from medical records. We used Kaplan Meier analysis to assess OS and PFS.&#x0D; Results: A total of 198 subjects met the inclusion criteria. Most MPE patients in this study were aged ≥60 years, male, smokers, pleural fluid lactate dehydrogenase value &lt;1500, ECOG 1, serum NLR value &lt;9, and high-risk cancer, namely lung cancer. The distribution of LENT scores for MPE patients was evenly distributed among the low, medium, and high-risk groups. Kaplan Meier analysis showed that the median OS based on LENT scores were 804 days, 275 days, and 161 days, respectively (log-rank test p = 0.000). The median PFS based on LENT scores were 715 days, 202 days, and 106 days, respectively (log-rank test p=0.000). The OS and PFS findings are longer than previous studies.&#x0D; Conclusion: Based on LENT scores, overall survival and progression-free survival MPE patients at tertiary hospitals in West Sumatera have a better prognosis compared to previous studies.

Comprehensive Bioinformatics Analysis Reveals PTPN1 (PTP1B) Is a Promising Immunotherapy Target Associated with T Cell Function for Liver Cancer.

Recently, PTP1B was identified as a novel immune checkpoint whose removal can unleash T cell responses. However, research on the influence of PTP1B as an immune regulator on liver cancer is limited. This study aimed to investigate the immunological correlation and function of PTP1B in liver cancer. The expression profiles and corresponding clinical information of liver cancer patients were obtained from the TCGA and ICGC databases. GSE146115 and GSE98638 retrieved from the GEO database were used for the single-cell RNA-seq analysis. The mRNA expression of PTP1B (PTPN1) was increased in patients with most malignancies (all p < 0.05), including liver cancer (p < 0.001). Furthermore, up-regulated PTPN1 was connected to advanced tumor stage (p < 0.05) and worse prognosis (p < 0.01) in liver cancer. Through Cox regression analysis, PTPN1 was considered as an independent prognosis factor of overall survival (p < 0.05) and acted as a high-risk factor (hazard ratio > 1). Gene function and pathway analysis suggested PTPN1 was involved in T cell-related immune responses. Moreover, a close relationship was also found between PTPN1 expression and immune checkpoints as well as immune cells, especially with T cell-related checkpoints (all p < 0.001) and T cells (all p < 0.001). Single-cell RNA-seq analysis further illustrated that the enrichment of PTPN1 in the T cell population may be linked to its exhaustion in the liver cancer microenvironment. Overall, PTPN1 (PTP1B) closely related to T cell may function as an immunotherapy target for liver cancer.

Effect of splenic hilar lymphadenectomy on locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ2 test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ2: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ2=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ2=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.

Prognosis factors for non-reversal of defunctioning ileostomy in patients with radical resection of rectal cancer

Objective: To examine the prognosis factors for non-reversal of defunctioning ileostomy in rectal cancer surgery. Methods: The data of 234 patients with rectal cancer undergoing radical resection and defunctioning ileostomy in the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2013 to June 2020 was analyzed retrospectively. There were 166 males and 68 females, aging (M(IQR)) 62(12) years (range: 33 to 89 years). Telephone following-up was conducted intensively in July 2021 to investigate whether stoma was reversed, causes of reversal failure, and tumor recurrence or metastasis after surgery. The non-reversal stoma was defined as stoma not being reversed during the follow-up period (more than 12 months). The χ2 test or Fisher's exact test was used to conduct a univariate analysis of clinical data related to reversal failure, and the factors with P<0.05 were selected into Logistic regression for multivariate analysis. Results: A total of 165 patients received stoma reversal postoperatively with an interval time of (6.5±2.4) months (range: 0.9 to 17.8 months), but 69 patients failed to closure of stoma. Univariate analysis showed that age, concomitant diseases, surgical methods, preoperative hemoglobin, preoperative carcinoembryonic antigen, tumor maximum diameter, depth of invasion, lymph node metastasis, TNM stage, anastomotic-related complications, postoperative tumor local recurrence or distant metastasis were associated with non-reversal of diverting ileostomy in rectal cancer surgery (all P<0.05). Multivariate analysis showed that age (OR=2.270, 95%CI: 1.150 to 4.479, P=0.018), open surgery (OR=7.249, 95%CI: 1.977 to 26.587, P=0.003), preoperative hemoglobin<120 g/L (OR=3.092, 95%CI: 1.566 to 6.105, P<0.01), anastomotic-related complications (OR=4.375, 95%CI: 1.686 to 11.349, P=0.002), postoperative local recurrence or distant metastasis (OR=7.065, 95%CI: 2.591 to 19.264, P<0.01) were independent prognosis factors for reversal failure of defunctioning stoma in rectal cancer surgery. Conclusions: There is a high risk of reversal failure of defunctioning ileostomy among rectal cancer patients with age>65 years, open surgery, preoperative hemoglobin<120 g/L, anastomotic-related complications, postoperative local recurrence or distant metastasis. Colorectal surgeons should fully evaluate the outcome and risk of reversal failure before making a decision of diverting ileostomy. Reducing anastomotic complications is helpful to the successful return of preventive ileostomy.

Short- and long-term outcomes after robotic and open liver resection for elderly patients with hepatocellular carcinoma: a propensity score-matched study.

Robotic liver resection (RLR) has increasingly been accepted as it has overcome some of the limitations of open liver resection (OLR), while the outcomes following RLR in elderly patients with hepatocellular carcinoma (HCC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of RLR vs. OLR in elderly HCC patients. Perioperative data of elderly patients (≥ 65years) with HCC who underwent RLR or OLR between January 2010 and December 2020 were retrospectively analyzed. A 1:2 propensity score-matched (PSM) analysis was performed to minimize the differences between RLR and OLR groups. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. Of the 427 elderly HCC patients included in this study, 113 underwent RLR and 314 underwent OLR. After the 1:2 PSM, there were 100 and 178 patients in the RLR and the OLR groups, respectively. The RLR group had a less estimated blood loss (EBL), a shorter postoperative length of stay (LOS), and a lower complications rate (all P < 0.05), compared with the OLR group before and after PSM. Univariable and multivariable analyses showed that advanced age and surgical approaches were not independent risk factors for long-term prognosis. The two groups of elderly patients who were performed RLR or OLR had similar OS (median OS 52.8 vs. 57.6months) and RFS (median RFS 20.4 vs. 24.6months) rates after PSM. RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.

Clinicopathological characteristics, survival outcome and prognostic factors of very young gastric cancer.

To explore the clinicopathological characteristics, survival outcomes, and prognosis of very young gastric cancer (GC). From January 1, 2011 to January 1, 2021, GC patients under 30years old treated in three tertiary hospitals were enrolled. Clinicopathological characteristics were summarized, prognostic factors and survival outcomes including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were retrospectively analyzed. One hundred patients were finally included, with a median age of 23years.73 (73.0%) were female. Most patients had initial symptoms of abdominal pain (66.0%). The most common tumor locations were gastric antrum (38.0%) and gastric body (37.0%). The main histological types were diffuse (81.0%) and poorly differentiated (91.0%). Most patients presented with stage III-IV disease (82.0%) at diagnosis and the common sites of metastasis were ovary (39.5%) and peritoneum (27.6%). The mOS of the whole group was 23.3months (95% CI 17.2-29.4). Moreover, the mOS of patients at stage I-II was not reached. The mOS of patients at stage III and stage IV was 40.6months (95% CI 10.2-70.9) and 10.3months (95% CI 8.9-11.6), respectively. The mDFS of stage I-III patients was 28.5months (95% CI 14.7-42.3), and the mPFS of the metastatic patients was 4.5months (95% CI 4.0-5.0). TNM stage (P = 0.005) and radical surgery (P = 0.001) were independent prognostic factors of overall survival. The very young GC were predominantly female, diffuse type, and advanced diagnosis. TNM stage and radical surgery were independent prognosis factors for overall survival.

Correlation between Characteristics of Lymph Node Metastasis and Prognosis of N1-N2 Stage Non-small Cell Lung Cancer

Objective: Patients with non-small cell lung cancer have prognostic heterogeneity, chief prognosis factor of them lymph node metastasis. Our study aimed to evaluate the correlation between lymph node ratio, the number of involved lymph node stations and skip-N2 metastasis and prognosis of N1-N2 stage non-small cell lung cancer. Methods: A total of 374 patients with N1 and N2 stage non-small cell lung cancer were retrospectively analyzed who underwent radical resection at the Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University from January 2012 to December 2019. Cox regression was conducted to identify the independent prognosis factors for N1-N2 stage non-small cell lung cancer. Survival curves were plotted by Kaplan-Meier method. Subgroup analyses were performed regarding proposals for the revision of the N descriptors in the 8th edition of the TNM classification. Results: Multivariate analysis of Cox regression model confirmed that smoking history, multiple-station lymph node metastasis and lymph node rate were independent prognosis factors for disease-free survival. Male, smoking history, multiple-station lymph node metastasis, lymph node ratio, adjuvant chemotherapy and targeted therapy were independent prognosis factors for overall survival. The 5-year overall survival was 57.4% in skip N2 group, while being 65.1% in N1 group (P=0.138) and 36.2% in the non-skip N2 group (P=0.007). Conclusion: Combined with lymph node ratio, the number of involved lymph node stations and skip metastasis, we can effectively predict the inter-subgroup survival difference.

ARNTL2 is a Prognostic Biomarker and Correlates with Immune Cell Infiltration in Triple-Negative Breast Cancer.

BackgroundTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with poor prognosis. The aberrant expression of circadian genes contributes to the origin and progression of breast cancer. The present study was designed to explore the potential function and prognosis value of circadian genes in TNBC.MethodsThe transcriptome data of circadian genes were downloaded from The Cancer Genomic Atlas (TCGA), GSE25066 and GSE31448 datasets. The differential expressed circadian genes between non-TNBC and TNBC patients were analysed by Wilcoxon test. Univariate and multivariate Cox regression analyses were employed to identify the prognostic circadian genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to study the biological functions of ARNTL2. The composition of 22 immune cells in the tumour samples was estimated with CIBERSORT algorithm. The correlations between ARNTL2 expression and tumour-infiltrating immune cells were evaluated by Spearman correlation coefficient.ResultsA total of 8 circadian genes were found to be differentially expressed between non-TNBC and TNBC, but only ARNTL2 has prognostic value. Multivariate Cox analysis identified that ARNTL2 was an independent prognosis factor for overall survival and relapse-free survival in TNBC patients. Functionally, ARNTL2 was mainly involved in immune response processes such as positive regulation of cytokine production, regulation of innate immune response, and cellular responses to molecules of bacterial origin. High expression of ARNTL2 was positively correlated with activated CD4 memory T cells, activated mast cells, and neutrophil infiltration and the expression of markers of neutrophils (ITGAM), dendritic cells (HLA-DRA, HLA-DPA1, ITGAM), Th1 (IL1B, STAT1), Th2 (IL13), Th17 (STAT3) and mast cells (TPSB2, TPSAB1).ConclusionARNTL2 may be linked with the functional modulation of the tumour immune microenvironment and serve as a potential biomarker for predicting the prognosis of TNBC patients.

Correlation between preoperative inflammatory biomarkers and postoperative pneumonia or long-term prognosis in patients with esophageal cancer after neoadjuvant therapy

Objective: To examine the correlation between neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio (NMR) for postoperative pneumonia or long-term overall survival in patients with esophageal cancer after neoadjuvant therapy. Methods: The clinical data of 137 patients, including 111 males and 26 females, with the age of (M(QR))61(10) years (range: 45 to 75 years), undergoing radical resection of esophageal cancer after neoadjuvant therapy admitted at Department of Thoracic Surgery, West China Hospital from January 2016 to May 2019 were analyzed retrospectively. The blood routine one or two days before surgery and the occurrence of pneumonia after surgery were collected via hospital information system. The absolute count of neutrophils, lymphocytes and monocytes was recorded, to calculate NLR, LMR and NMR. The survival of patients was recorded systematically via follow-up. In the first part, the influencing factors of postoperative inflammation were analyzed, to group the patients into two groups according to the occurrence of postoperative pneumonia. χ2 test, t-test or rank-sum test were conducted for inter-group comparison. In the second part, cutoff values of inflammatory biomarkers were obtained with the receiver operating characteristic (ROC) curve and grouped, with postoperative pneumonia as endpoint criteria. Independent factors correlated with postoperative pneumonia were determined through univariate and multivariate Logistic regression analysis. In the third part, the analysis on prognosis factors was carried on, with the survival as endpoint criteria. Cutoff values of inflammatory biomarkers were obtained with X-Tile software and grouped. The survival analysis was carried on with univariate and multivariate Cox proportional hazards regression model, and the Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Median follow-up time was 614 (299) days (range: 382 to 1 612 days). Cutoff values of NLR, LMR, and NMR obtained via the ROC curve were 3.0, 3.9, and 6.2, respectively. According to the multivariate Logistic regression analysis, NLR>3.0 (OR=2.740, 95% CI: 1.221 to 6.152, P=0.015) and LMR>3.9 (OR=0.140, 95% CI: 0.022 to 0.890, P=0.037) were independent prognosis factors for postoperative pneumonia in patients with esophageal cancer after neoadjuvant therapy. Cutoff values of NLR, LMR, and NMR obtained with X-Tile software were 3.3, 4.2, and 7.2, respectively. Through multivariate Cox proportional risk regression analysis, late tumor ypTNM staging (8th AJCC) (HR=2.087, 95% CI:1.079 to 4.038, P=0.029), poor pathologic response (HR=2.251, 95% CI: 1.117 to 4.538, P=0.023), and LMR>4.2 (HR=0.347, 95% CI: 0.127 to 0.946, P=0.039) could be independent prognosis factors for overall survival. Kaplan-Meier survival analysis indicated that the overall survival of patients with LMR ≤4.2 was worse (P=0.002), with the 1-year overall survival rate of 82.9%, and the 1-year overall survival rate of patients with LMR>4.2 was 94.6%. Conclusion: Preoperative LMR ≤3.9 and NLR>3.0 can be considered as independent prognosis factors for postoperative pneumonia, while LMR≤4.2 as one of independent prognosis factors for overall survival.

O11 Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an important clinical and prognostic indicator in pancreatic cancer

Abstract Introduction Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a cell adhesion molecule and one of the potential metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cell adhesion. The present study investigated the clinical, pathological and prognostic value of ALCAM in patients with pancreatic cancer. Method Pancreatic cancer tissues (n = 223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts. The expression was analysed against clinical, pathological and clinical outcome of the patients. We validated our findings with an available TCGA database (n = 117), including correlations with the ALCAM interactive partners. Result Pancreatic cancer tissues had significantly higher levels of ALCAM transcript than normal tissues (P &amp;lt; 0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P = 0.018), finding also supported by ROC analysis (P = 0.016). Multivariant analysis showed ALCAM as an independent prognosis factor for overall survival (hazardous ratio 5.485), with both nodal status and TNM staging contributing to the model (HR 2.578 and 3.02 respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P = 0.021, with vs without tumour embolism). ALCAM significantly correlated with its interactive protein partners including CD6 and ITGB1, but not L1CAM. Conclusion ALCAM/CD166 expression is aberrant in pancreatic cancer and the raised expression is an independent prognostic factor for the survival of the patients and the microvessel embolism by cancer cells. Take-home Message ALCAM is a prognostic indicator for survival and tumour embolism in pancreatic cancer

YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. It thrives in a malnourished environment; however, little is known about the mechanisms by which PDAC cells actively promote aerobic glycolysis to maintain their metabolic needs. Gene Expression Omnibus (GEO) was used to identify differentially expressed miRNAs. The expression pattern of miR-30d in normal and PDAC tissues was studied by in situ hybridization. The role of miR-30d/RUNX1 in vitro and in vivo was evaluated by CCK8 assay and clonogenic formation as well as transwell experiment, subcutaneous xenograft model and liver metastasis model, respectively. Glucose uptake, ATP and lactate production were tested to study the regulatory effect of miR-30d/RUNX1 on aerobic glycolysis in PDAC cells. Quantitative real-time PCR, western blot, Chip assay, promoter luciferase activity, RIP, MeRIP, and RNA stability assay were used to explore the molecular mechanism of YTHDC1/miR-30d/RUNX1 in PDAC. Here, we discover that miR-30d expression was remarkably decreased in PDAC tissues and associated with good prognosis, contributed to the suppression of tumor growth and metastasis, and attenuation of Warburg effect. Mechanistically, the m6A reader YTHDC1 facilitated the biogenesis of mature miR-30d via m6A-mediated regulation of mRNA stability. Then, miR-30d inhibited aerobic glycolysis through regulating SLC2A1 and HK1 expression by directly targeting the transcription factor RUNX1, which bound to the promoters of the SLC2A1 and HK1 genes. Moreover, miR-30d was clinically inversely correlated with RUNX1, SLC2A1 and HK1, which function as adverse prognosis factors for overall survival in PDAC tissues. Overall, we demonstrated that miR-30d is a functional and clinical tumor-suppressive gene in PDAC. Our findings further uncover that miR-30d is a novel target for YTHDC1 through m6A modification, and miR-30d represses pancreatic tumorigenesis via suppressing aerobic glycolysis.

Expression of CD44 variant 9 induces chemoresistance of gastric cancer by controlling intracellular reactive oxygen spices accumulation.

CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), resulting in promoted tumor growth. CD44v9 and GPx2 expression were investigated by immunohistochemistry in resected specimens from 193 gastric cancer (GC) patients without preoperative chemotherapy and in pretreatment biopsy specimens from 29 GC patients with preoperative chemotherapy. We analyzed the relationship between CD44v9 expression and clinicopathological factors, prognosis, and pathological response to chemotherapy. In GC cell lines, we examined the relationship between CD44v9 expression and chemotherapeutic sensitivity. In patients without preoperative chemotherapy, CD44v9 expression was significantly associated with depth of invasion, lymphatic permeation, vascular invasion, distant metastasis and GPx2 expression. In multivariate analysis, CD44v9 expression was an independent poor prognosis factor for overall survival and recurrence-free survival. In patients with preoperative chemotherapy, CD44v9 expression was significantly associated with worse pathological response and GPx2 expression. In GC cell lines, downregulation of CD44v9 expression enhanced chemotherapeutic sensitivity to 5-fluorouracil with changing GSH and ROS levels. CD44v9-positive expression was associated with chemotherapeutic resistance by controlling intracellular accumulated ROS, suggesting that CD44v9 may be a predictive biomarker for chemotherapy in GC.

Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway.

BackgroundThe small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression.MethodsImmunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo.ResultsBoth mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects.ConclusionOur data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.

Oropharyngeal cancer: First relapse description and prognostic factor of salvage treatment according to p16 status, a GETTEC multicentric study.

Although Human Papilloma Virus (HPV)-driven oropharyngeal cancer (OPC) prognosis is significantly better than that of other head and neck cancers, up to 25% of cases will recur within 5 years. Data on the pattern of disease recurrence and efficiency of salvage treatment are still sparse. Observational study of all recurrent OPCs diagnosed, following a curative intent treatment, in seven French centers from 2009 to 2014. p16 Immunohistochemistry was used to determine HPV status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival was examined using Kaplan-Meier and multivariate Cox regression modeling. 350 recurrent OPC patients (246 p16-negative and 104 p16-positive patients). The site of recurrence was more frequently locoregional for p16-negative patients (65.4% versus 52.9% in p16-positive patients) and metastatic for p16-positive patients (47.1% versus 34.6% in p16-patients, p=0.03). Time from diagnosis to recurrence did not differ between p16-positive and p16-negative patients (12 and 9.6 months, respectively, p-value=0.2), as the main site of distant metastasis (all p-values ≥0.10). Overall and relapse-free survival following the first recurrence did not differ according to p16 status (p-values from log-rank 0.30 and 0.40, respectively). In multivariate analysis, prognosis factors for overall survival in p16-negative patients were distant metastasis (HR 2.11, 95% CI 1.30-3.43) and concurrent local and regional recurrences (HR 2.20, 95% CI 1.24-3.88). With the exception of the initial site of recurrence, the pattern of disease relapse and the efficiency of salvage treatment are not different between p16-positive and negative OPCs.

P-226 Analysis of Hispanic Latino American patients with colorectal cancer, clinical features and laterality as a prognosis factor of overall survival

Colorrectal cancer (CCR) is one of the leading causes of death in the world. The laterality of the primary tumor has been divided in right-sided colon, and left-sided colon showing promising results in terms of overall survival regarding right side colon, nevertheless few information exists regarding Hispanic Latino American population. The objective was to evaluate the impact of the laterality on the overall survival of Mexican patients diagnosed metastatic colorectal adenocarcinoma treated at the National Cancer Institute.

Long-term efficacy of robotic radical total gastrectomy for gastric cancer and analysis of prognostic factors

Objective: To analyze long-term outcomes and prognostic factors of gastric cancer patients after robotic radical total gastrectomy. Methods: A retrospective case-control study was conducted. Inclusion criteria: (1) receiving robotic radical total gastrectomy; (2) gastric adenocarcinoma was confirmed by postoperative pathology; (3) no previous history of other malignant tumors; (4) no preoperative chemotherapy or radiation therapy performed. Exclusion criteria: (1) age <18 years old or age >80 years old;(2)distant metastasis before surgery, or palliative surgery; (3) conversion to laparotomy;(4) R1 or R2 resection; (5)emergency surgery; (6) remnant gastric cancer or recurrence; (7)died of severe complications during hospitalization or within 1 month after surgery. Overall survival rates (OS) and disease-free survival rates (DFS) were evaluated using the Kaplan-Meier method. Cox regression analysis was used to identify prognosis factors for overall survival. Results: According to the above criteria, 166 gastric cancer patients who underwent robotic radical total gastrectomy between March 2010 and November 2018 were included in this study. Roux-en-Y reconstruction was performed in all patients. Reconstruction were achieved using extracorporeal method through a minilaparotomy in 149 case and intracorporeal anastomosis in 17 cases. The number of harvested lymph nodes was (34.8±17.5), and the number of harvested lymph nodes at group 2 was (10.1±6.7). The number of patients with lymph node metastasis of group 2 was 73 (44.0%). The median follow-up time was 25 months (range 2-109). There were 55 (33.1%) cases of recurrence during follow-up. The 3- and 5-year overall survival rates were 55.8% and 46.2% respectively. The 3- and 5-year disease-free survival rates were 53.4% and 45.4% respectively. The 5-year overall survival rates grouped based on TNM stage were 78.9% for stage I, 58.5% for stage II, and 37.1% for stage III. The 5-year disease-free survival rates grouped based on TNM stage were 78.9% for stage I, 59.2% for stage II, and 34.6% for stage III. Univariate analysis suggested that TNM stage, the number of harvested lymph nodes and number of harvested lymph nodes at group 2 were associated with overall survival rates (all P<0.05). Multivariate analyses revealed that TNM stage (P<0.001; stage IIIB: HR=5.357, 95%CI:1.182 to 24.275; stage IIIC: HR=11.937, 95%CI: 2.677 to 53.226) and number of harvested lymph nodes at group 2 (P=0.034; 6-10: HR=0.562,95%CI:0.326 to 0.969; >10: HR=0.388, 95%CI: 0.176 to 0.857) were independent prognostic factors for overall survival. Conclusion: The long-term outcomes of robotic radical total gastrectomy were satisfactory. TNM stage and number of harvested lymph nodes at group 2 were independent prognostic factors for overall survival.

Ramucirumab for patients with intermediate-stage hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): Pooled results from two phase III studies (REACH and REACH-2).

549 Background: Intermediate-stage HCC, as defined as Barcelona Clinic Liver Cancer (BCLC) Stage B, is a heterogeneous disease in terms of liver function and tumor load. REACH (NCT01140347) and REACH-2 (NCT02435433) investigated ramucirumab (RAM) in patients (pts) with HCC after prior sorafenib (SOR), with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: All pts had HCC (BCLC stage C or B disease refractory/not amenable to locoregional therapy), Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or Placebo (P) Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was performed. Prognosis of BCLC staging in overall survival (OS) was evaluated by multivariate Cox PH model (adjusted for baseline AFP and treatment (trt) arm); Trt effects in BCLC stage B and C by Cox PH model; median OS/PFS were estimated by Kaplan-Meier method. Objective response rate (ORR) per RECIST v1.1, disease control rate (DCR), and adverse events (AEs) were also reported by BCLC. Liver function was assessed at baseline and prior to each trt with the Albumin-Bilirubin (ALBI) linear predictor. Results: Baseline characteristics were generally balanced between trt arms in each BCLC stage. BCLC staging trended as an independent prognosis factor for OS [B v C; HR = 0.756 (0.546, 1.046)]. A consistent trt benefit for RAM v P was observed across staging (Table). Grade ≥3 AEs were consistent with observations from both individual studies; hypertension was the most frequent grade ≥3 AE. No difference in liver function, as measured by ALBI, was observed between trt arms in either BCLC stage. Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit irrespective of BCLC stage. RAM was well tolerated and did not alter liver function compared to P. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

Correlation between Lymph Node Ratio and Clinicopathological Features and Prognosis of IIIa-N2 Non-small Cell Lung Cancer

背景与目的淋巴结解剖位置是非小细胞肺癌N分期的基础，但Ⅲa-N2非小细胞肺癌生存差异显著，淋巴结转移率或与非小细胞肺癌预后有关，或可成为Ⅲa-N2非小细胞肺癌亚组评估指标。本研究探究淋巴结转移率与Ⅲa-N2非小细胞肺癌临床病理特征和生存的相关性。方法纳入北京大学肿瘤医院胸外二科2006年1月-2016年12月期间直接手术的288例Ⅲa-N2非小细胞肺癌患者，卡方检验分析淋巴结转移率与临床病理特征相关性，Cox回归模型分析生存危险因素，Kaplan-Meier方法绘制生存曲线。结果低淋巴结转移率139例，高淋巴结转移率149例，淋巴结转移率与腺癌（χ2=5.924, P=0.015）、最高组N2淋巴结转移（χ2=46.136, P < 0.001）、多个N2淋巴结转移（χ2=59.347, P < 0.001）、多站N2淋巴结转移（χ2=77.387, P < 0.001）及跳跃性N2淋巴结转移（χ2=61.524, P < 0.001）显著相关，与淋巴结清扫总数无关（χ2=0.537, P=0.464）。Cox回归模型多因素分析显示，腺癌（P=0.008）、多站N2淋巴结转移（P=0.025）和淋巴结转移率（P=0.001）是Ⅲa-N2非小细胞肺癌无病生存的独立危险因素，高淋巴结转移率组5年无病生存率为18.1%，低淋巴结转移率组5年无病生存率为44.1%。淋巴结转移率（P < 0.001）是Ⅲa-N2非小细胞肺癌总生存的独立危险因素，高淋巴结转移率组5年总体生存率为36.7%，低淋巴结转移率组5年总体生存率为64.1%。结论淋巴结转移率与病理类型、跳跃性N2淋巴结转移、纵隔淋巴结转移个数、纵隔淋巴结转移站数、最高组N2淋巴结转移密切相关。淋巴结转移率是Ⅲa-N2非小细胞肺癌生存的独立危险因素，可更有效地预测Ⅲa-N2非小细胞肺癌亚组间的生存差异。