Independent Risk Factor For OS Research Articles

Expression of CX3CL1 and CCL28 in Spinal Metastases of Lung Adenocarcinoma and Their Correlation with Clinical Features and Prognosis.

Lung adenocarcinoma is the most common non-small-cell lung cancer. In this paper, we aim to investigate the expression of chemokine ligand 1 (cx3cl1) and chemokine ligand 28 (CCL28) in spinal metastases of lung adenocarcinoma and their correlation with clinical features and prognosis. We analyzed the clinical data of 40 patients with lung adenocarcinoma and spinal metastases who underwent surgery in our hospital from January 2018 to January 2021 retrospectively. The expression levels of cx3cl1 and CCL28 in bone metastases were detected by immunohistochemistry, and the staining results were sorted and classified. Combined with the follow-up results and clinicopathological data, we statistically analyzed the expression of cx3cl1 and CCL28 in spinal bone metastases and their correlation with prognosis. Among the 40 patients with spinal metastasis of lung adenocarcinoma, 7 cases were strongly positive for cx3cl1, 25 cases were moderately positive, and 8 cases were weakly positive and negative. CCL28 was strongly positive in 9 cases, moderately positive in 26 cases, weakly positive and negative in 5 cases. The expression of cx3cl1 was correlated with ECOG score (P = 0.005) and visceral organ metastasis (P = 0.004), but not with age, sex, and the number of bone metastases (P > 0.05). The expression of CCL28 was correlated with ECOG score (P = 0.022) and visceral organ metastasis (P = 0.003), but not with age, sex, and the number of bone metastases (P > 0.05). The OS of patients with strong cx3cl1 positive was significantly shorter than that of patients with medium positive and weak positive (P < 0.001). The survival time was 10, 7, and 4 months, respectively. The OS of patients with strong positive CCL28 was significantly shorter than that of patients with medium positive and weak positive CCL28 (P = 0.004). The survival time was 12, 8, and 4 months, respectively. Univariate analysis showed that ECOG score (P < 0.001), chemotherapy (P = 0.032), visceral organ metastasis (P = 0.002), cx3cl1 expression (P < 0.001), and CCL28 expression (P = 0.004) were the risk factors of OS. Cox regression analysis showed that the expression of cx3cl1 was an independent risk factor for OS in patients with spinal metastasis of lung adenocarcinoma (P = 0.044). Cx3cl1 and CCL28 were highly/strongly positive in spinal metastases of lung adenocarcinoma. The level of cx3cl1 can be used as an index to judge the clinical prognosis of patients with spinal metastasis of lung adenocarcinoma, which can better reflect the prognosis of patients than CCL28.

Development and Validation of a Novel Histone Acetylation-Related Gene Signature for Predicting the Prognosis of Ovarian Cancer.

Histone acetylation is one of the most common epigenetic modifications, which plays an important role in tumorigenesis. However, the prognostic role of histone acetylation-regulators in ovarian cancer (OC) remains little known. We compared the expression levels of 40 histone acetylation-related genes between 379 OC samples and 88 normal ovarian tissues and identified 37 differently expressed genes (DEGs). We further explored the prognostic roles of these DEGs, and 8 genes were found to be correlated with overall survival (p < 0.1). In the training stage, an 8 gene‐based signature was conducted by the least absolute shrinkage and selector operator (LASSO) Cox regression. Patients in the training cohort were divided into two risk subgroups according to the risk score calculated by the 8-gene signature, and a notable difference of OS was found between the two subgroups (p < 0.001). The 8-gene risk model was then verified to have a well predictive role on OS in the external validation cohort. Combined with the clinical characteristics, the risk score was proved to be an independent risk factor for OS. In conclusion, the histone acetylation-based gene signature has a well predictive effect on the prognosis of OC and can potentially be applied for clinical treatments.

Haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission.

Background:The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods:A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results:Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion:Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

Linitis plastica: current prognostic implication of a classic concept.

Despite having been described for several centuries linitis plastica's (LP) prognostic implication remain unclear. To analyze the impact of LP on the survival of patients undergoing gastrectomy for gastric adenocarcinoma. A single-center retrospective study of cases of LP diagnosed and confirmed by pathological anatomy has been carried out in a third-level center for 5 years. They were grouped into Linitis Plastica (LP), diffuse non-LP carcinomas (DNLP) and other adenocarcinomas (ADC). 199 gastrectomies performed in the same period of time were included in the comparative analysis. With a median follow-up of 54.5 months (95% CI: 37.0-65.0), the median survival of LP was 14 months (95% CI: 9-27) significantly lower (p = 0.002) compared to DNLP 51.5 months (95% CI: 25-70) and the rest of ADC 62 months (95% CI: 43-68). The OS at 1, 3 and 5 years was statistically worse in the LP group (69, 15, 8%) compared to DNLP (82, 54, 44%) and ADC (89, 63, 54%) (p = 0.073, p <0.001, p <0.001). In the multivariate analysis, LP was identified as an independent risk factor for OS with an HR of 3.26 (p = 0.001). LP is an independent prognostic factor associated with higher mortality in gastric cancer.

BIRC5 Modulates PD-L1 Expression and Immune Infiltration in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most prevalent thoracic cancer with the highest incidence and mortality worldwide. Baculoviral IAP Repeat Containing 5 (BIRC5) is well studied in many malignancies, its prognosis value and correlation with the tumor microenvironment (TME) in LAUD remains largely elusive.Methods: The Wilcoxon signed-rank test and logistic regression were used to evaluate the relationship between clinical features and BIRC5 expression in LUAD. To assess the impact of BIRC5 on prognosis, the Kaplan-Meier plotter analysis and Cox regression were used, as well as a receiver operating characteristic (ROC) curve and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were recruited to predict the association between BIRC5 and immune cell infiltrations. Furthermore, qRT-PCR and western bolt were utilized to confirm gene expression on mRNA and protein levels. The proliferation of A549 and H1299 cells was evaluated using CCK8 and EdU assay. Cell mobility was tested by transwell assay and wound healing assay. Detection of PD-L1 and infiltrated CD8 T cells in xenograft tumors was done by flow cytometry.Results: BIRC5 expression was found to be substantially greater in LUAD patients. According to KM-plotter analysis, patients with high levels of BIRC5 had shorter survival rates. Multivariate Cox analysis revealed that elevated BIRC5 expression was an independent risk factor for OS and PFS in LUAD patients. High BIRC5 expression was predicted to be associated with chemokine activity and immune cell chemotaxis, whereas ssGSEA suggested that BIRC5 is highly associated with CD8 T cell infiltration and PD-L1 levels. In vitro experiments suggested overexpression of BIRC5 promoted the proliferation, mobility, and PD-L1 level of A549 cells, and vice versa in H1299 cells. Furthermore, in vivo study suggested elevated tumor weight and PD-L1 levels in xenograft tumors generated from LLC cells with overexpressed BIRC5.Conclusion: BIRC5 promotes lung adenocarcinoma progression by modulating PD-L1 expression and inducing tumor immune evasion.

Effect of surgery and radiotherapy on overall survival in patients with chondrosarcoma: A SEER-based study.

Chondrosarcoma is an orthopedic malignancy, and the purpose of this study was to evaluate the effect of surgery and radiotherapy (RT) on the survival of patients with chondrosarcoma. Data were obtained from the SEER database for patients diagnosed with chondrosarcoma between 1988 and 2015. All patients were divided into surgery, RT, surgery + RT, and no surgery/no RT groups. Kaplan-Meier curves were used to analyze the overall survival and cancer-specific survival of patients in different treatment groups. The propensity score matching was used to balance baseline covariates between patients in the surgery and surgery + RT groups and in the RT and surgery + RT groups. Data from 3756 patients with chondrosarcoma were included in this study. The number of patients who underwent surgery, RT, surgery + RT, and no surgery or RT was 2885 (76.8%), 112 (3.0%), 403 (10.7%), and 356 (9.5%), respectively. Multivariate Cox regression models showed that treatment modality was independent risk factor for OS and CSS. Before PSM, Kaplan-Meier curves showed that OS and CSS were highest in the surgery group and lowest in the RT group. After PSM, although there was no significant difference in OS (p = .13) and CSS (p = .22) between the surgery and surgery + RT group, OS was longer in the surgery group than in the surgery + RT group. Additionally, OS (p < .001) and CSS (p = .009) were longer in the surgery + RT group than in the RT group after PSM. Surgical resection was the key approach for the treatment of chondrosarcoma, while RT confers no significant advantage in improving patient survival time.

Construction and validation of a prognostic model for stage IIIC endometrial cancer patients after surgery

BackgroundTo explore the most predictive lymph node (LN) scheme for stage IIIC endometrial cancer (EC) patients after hysterectomy and develop a scheme-based nomogram. MethodsData from 2626 stage IIIC EC patients, diagnosed between 2010 and 2014, were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. The predictive ability of four LN schemes was assessed using C-index and Akaike information criterion (AIC). A nomogram based on the most predictive LN scheme was constructed and validated. The comparison of the predictive ability between nomogram and FIGO stage was conducted using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). ResultsFIGO stage (stage IIIC1/stage IIIC2) was not an independent risk factor for OS in stage IIIC EC patients (P = 0.672) and log odds of positive lymph nodes (LODDS) had the best predictive ability (C-index: 0.742; AIC: 8228.95). A nomogram based on LODDS was constructed and validated, which had a decent C-index of 0.742 (0.723–0.762). The nomogram showed a better predictive ability than that of the FIGO staging system. ConclusionFIGO IIIC1/FIGO IIIC2 could not differentiate the prognosis for stage IIIC EC patients. We developed and validated a nomogram based on LODDS to predict OS for post-operative patients with stage IIIC EC.

P-P13 Long-term outcome after portal vein resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matched analysis

Abstract Background Portal vein resection (PVR) with pancreaticoduodenectomy (PD) is often performed to achieve clear margins for patients with vascular involvement in pancreatic ductal adenocarcinoma (PDAC). However, there is evidence to suggest that patients undergoing PVR often have more advanced cancers, therefore the impact of PVR on survival and recurrence remains unclear. The aim of this study is to assess overall (OS) and recurrence free (RFS) survival in patients who underwent PVR during PD, with particular attention to margin positivity. Methods A retrospective analysis was performed on 638 patients who underwent PD during a 12-year period. Exclusion criteria included PD for non-PDAC tumours, neoadjuvant chemotherapy or intra-operative radiotherapy. 374 patients were included in the study (90 PVR and 284 non-PVR). Patient characteristics and histopathological factors associated with OS and RFS were then evaluated using univariate and multivariate Cox regression analyses. 270 patients (90 PVR and 180 non-PVR), were matched by propensity score based on perineural invasion, pT and pN staging. The Kaplan-Meier method was used to calculate survival and log-rank tests. Results Resection margin positivity was associated with shorter OS and RFS (p &amp;lt; 0.0001), and the superior mesenteric vein (SMV) margin was the most significant risk factor for survival on competing risks analysis. Absent adjuvant chemotherapy, nodal metastasis and margin positivity were independent risk factors for OS and RFS on multivariate analysis. PVR was associated with higher intra-operative blood loss (p = 0.009), but was not associated with increased length of stay, complications or readmissions. PVR patients had increased pT staging, nodal metastasis and perineural invasion, however, there was no difference in OS (p = 0.551) or RFS (p = 0.256) between PVR and non-PVR after propensity matching. Conclusions Positive resection margins are associated with shorter survival times, and the SMV margin is the most significant prognostic indicator for overall survival and recurrence compared to other margins. PVR is a relatively safe procedure, however, it does not achieve the intended survival benefits of complete margin clearance. The impact on survival for margin positivity, particularly the SMV margin, and nodal metastasis should be considered when making decisions with regards to vein resection and adjuvant treatments.

The Clinical Utility of the Geriatric Nutritional Risk Index in Predicting Postoperative Complications and Long-Term Survival in Elderly Patients with Colorectal Cancer after Curative Surgery.

Simple SummaryElderly cancer patients usually suffer with malnutrition. Preoperative malnutrition has been considered a poorer prognostic factor in cancer treatment. The geriatric nutritional risk index (GNRI) is a simple tool for predicting the risk of morbidity and mortality in elderly patients by using albumin, height, and body weight parameters. In this study, we evaluated whether GNRI is a reliable marker for postoperative complications and long-term survival. By retrospectively evaluating 1206 CRC patients aged over 75 years who underwent curative-intent surgery at Chang Gung Memorial Hospital, there were significantly more postoperative complications in the low GNRI group (p < 0.001) and GNRI was an independent risk factor for postoperative complications (HR: 1.774, p = 0.037). Overall survival and disease-free survival were significantly worse in the low GNRI group (both p < 0.001) and a GNRI < 98 was statistically identified as an independent prognostic factor for survival. Conclusively, GNRI can be a reliable biomarker in clinical practice.Research on the relationship between the geriatric nutritional risk index (GNRI) and postoperative complications/oncological outcomes in elderly colorectal cancer (CRC) patients is limited. This study investigated the prognostic value of the GNRI in aged CRC patients. We retrospectively analyzed 1206 consecutive CRC patients aged over 75 years who underwent curative-intent surgery from January 2008 to December 2015 and categorized them into high GNRI (≥98) and low GNRI (<98) groups according to a receiver operating characteristic (ROC) curve analysis. Uni- and multivariate logistic regression analysis were used to explore the association of the GNRI with postoperative complications. Kaplan–Meier survival analyses and the Cox proportional hazard model were used to explore the association between GNRI and survival. We discovered that GNRI is an independent risk factor for postoperative complications (HR: 1.774, p = 0.037). Surgical site infection, wound dehiscence and pneumonia were more common in patients with GNRI < 98. Survival analysis showed significantly worse overall survival and disease-free survival in the low GNRI group (both p < 0.001). In the multivariate analysis, GNRI < 98 was an independent risk factor for OS (HR: 1.329, p = 0.031) and DFS (HR: 1.312, p = 0.034). Thus, preoperative GNRI can be effectively used to predict postoperative complications and long-term survival in elderly CRC patients after curative surgery.

Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis

目的评价异基因造血干细胞移植（allo-HSCT）治疗急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的疗效及预后因素，分析AML-MRC患者基因突变谱系并探讨影响移植预后的分子生物学特征。方法对2006年至2020年于中国医学科学院血液病医院接受allo-HSCT的75例AML-MRC患者进行回顾性分析。将75例患者分为：H组［既往有骨髓增生异常综合征（MDS）或MDS/骨髓增殖性肿瘤（MPN）病史］、C组（新诊断的AML-MRC伴MDS相关细胞遗传学异常）和M组（新诊断的AML-MRC伴多系发育异常），分析三组患者临床特征差异以及对移植预后的影响。对43例患者行骨髓靶向二代测序（137个基因）。结果①75例AML-MRC患者，男41例，女34例，中位年龄41（18～56）岁，中位随访时间为35（95％ CI 30～49）个月，中位总生存（OS）时间为78个月（95％CI 23个月～未达到）。移植后3年OS率为57.1％（95％CI 45.6％～71.4％），无事件生存（EFS）率为52.0％（95％CI 40.8％～66.1％），累积复发率（CIR）为26.8％（95％CI 16.6％～30.0％），移植相关死亡率（TRM）为22.7％（95％ CI 13.2％～33.8％）。多因素分析显示，移植前处于非第1次完全缓解（CR1）状态是移植后OS和EFS的独立危险因素。影响OS的独立危险因素还包括−5/5q−染色体核型异常、移植后未发生慢性移植物抗宿主病（慢性GVHD）。②75例患者中H组59例（78.7％），其中20例转化为白血病（转白）前曾接受去甲基化药物治疗；C组9例（12.0％），M组7例（9.3％）。M、H、C组移植后3年OS率分别为71.4％（95％CI 44.7％～100.0％）、55.0％（95％CI 41.8％～72.5％）、55.6％（95％ CI 31.0％～99.7％）（P＝0.700），EFS率分别为71.4％（95％CI 44.7％～100.0％）、46.5％（95％CI 34.0％～63.8％）、55.6％（95％CI 31.0％～99.7％）（P＝0.600）；原发性AML-MRC与继发性AML-MRC相比，移植后3年OS、EFS率差异无统计学意义［61.9％（95％CI 41.9％～91.4％）对55.0％（95％ CI 41.8％～72.5％），P＝0.600；61.9％（95％CI 41.9％～91.4％）对46.5％（95％CI 34.0％～63.8％），P＝0.400］。转白前接受去甲基化治疗（20例）与未接受去甲基化治疗（39例）患者比较，转白时间差异无统计学意义［195（16～937）d对162（9～3167）d，P＝0.804］，且两组患者OS和EFS差异无统计学意义（P＝0.400，P＝0.700）。③对43例（57.3％）患者骨髓样本行二代基因测序，共发现73个突变类型，检出率最高的是U2AF1（11例，25.6％），其他检出率>10％的突变包括RUNX1（10例，23.3％）、NRAS（10例，23.3％）、ASXL1（6例，14.0％）、PTPN11（5例，11.6％）、TET2（5例，11.6％）。单因素分析显示U2AF1［P＝0.875，HR＝1.110（95％ CI 0.295～4.195）］、RUNX1［P＝0.685，HR＝0.728（95％ CI 0.157～3.375）］、NRAS［P＝0.919，HR＝0.923（95％CI 0.196～4.334）］突变对移植后OS没有影响。结论−5/5q−染色体异常、未发生慢性GVHD、移植前非CR1状态是影响AML-MRC患者移植后OS的独立危险因素；MHC亚组分类不是影响移植预后的因素；去甲基化药物治疗可能无助于延缓MDS患者转白以及延长移植后OS期。

ARHGAP6 EXPRESSION IS ASSOCIATED WITH MOLECULAR RISK AND IMPACTS CLINICAL OUTCOMES IN ACUTE MYELOID LEUKEMIA

Despite the advances in the large-scale generation of genomic data from acute myeloid leukemia (AML) patients, much effort is still needed to convert these data into biological functions, which may pave avenues for the discovery of new prognostic markers and therapeutic targets. In a previous study, four cytoskeleton-related genes (ARHGAP6, EZR, MAP3K11 and PAK1) were identified as a prognostic factor in AML. In the present study, we detail the prognostic impact, as well as its functional genomic associations, of the ARHGAP6 gene in AML patients. Clinical and genomic data were obtained from the TCGA AML cohort (n = 173). The clinical impact (overall survival [OS] and disease-free survival [DFS]) for ARHGAP6 expression was investigated by the proportional hazards Cox regression model. Functional genomic analyzes were performed by gene set enrichment analysis (GSEA) and Gene Ontology (GO) from differentially expressed (DEG) genes obtained from the Galaxy tool. All p values were two sided with a significance level of 5%. ARGHAP6 expression was higher in the intermediate and high molecular risk groups in AML patients (all p < 0.01). High ARGHAP6 expression was identified as an independent risk factor for OS (HR = 1.92; p = 0.001) and DFS (HR = 1.96; p = 0.01) when analyzed with confounders, age, gender, white blood cell count, and molecular risk. In the GSEA, a total of 30 cellular and molecular events were found to be positively enriched in high ARHGAP6-expressing AML patients, which we highlighted the signaling pathways: IL6/JAK2/STAT3 (NES: 1.62; p < 0.001), NOTCH (NES: 1.60; p < 0.001), KRAS (NES: 1.59; p < 0.001), IL2/STAT5 (NES: 1.51; p < 0.001), TGF BETA (NES: 1.39; p = 0.03) and BETA CATENIN SIGNALING (NES: 1.36; p = 0.04). In GO analyses, high ARHGAP6 expression was associated with important processes for cancer development and progression such as cell signaling mediated by surface receptors, signal transduction, linkage to growth factors, and regulation of cell population proliferation (all p < 0.001). ARHGAP6 is a RhoGAP that acts converting RhoGTPases in its inactive GDP-bound state, which may regulate the interactions of signaling molecules with the actin cytoskeleton. It promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. The role of ARHGAP6 is still poorly established in cancer, but it is known to modulate pathways of RhoGTPases. In this sense, our study is a pioneer in the identification of this gene in processes related to neoplastic hematopoiesis, which will guide future investigations. ARHGAP6 gene expression was identified as an independent marker of poor prognosis in AML patients. The GSEA suggested that high ARHGAP6 expression is associated with activation of relevant processes to the malignant phenotype of AML. FAPESP, CNPq and CAPES.

Prognostic significance of pathological sub-classification of pT3 rectal cancer.

Patients with pT3 rectal cancer represent a heterogeneous prognostic group. A more accurate histological sub-classification of pT status has been suggested as an improvement of the TNM staging system. The aim of the study was to evaluate the prognostic implication of a histopathologic sub-classification of pT3 rectal cancer. In this retrospective single-center study, pT3 rectal cancer patients who underwent surgery from January 2000 to December 2018 were evaluated. The maximum depth of tumor invasion beyond the muscularis propria was recorded. A ROC curve identified the best prognostic cutoff value to classify patients in two prognostic groups. Survival curves were estimated by the Kaplan-Meier method, and univariate and multivariate analyses with the Cox regression model were used to find independent factors influencing survival. Overall, 203 patients were included. Four millimeters was identified as the best cutoff value: 82 patients showed a depth of invasion < 4mm (group A) and 121 ≥ 4mm (group B). Both the estimated 5-year OS and DFS were statistically better in group A than in group B (OS: 83.9% vs 62.2%, p < 0.01; DFS: 78.3% vs 40.6%, p < 0.01). The depth of tumor invasion was an independent risk factor for OS (HR 2.25, 95% CI 1.26-3.99, p = 0.006) and DFS (HR 2.30, 95% CI 1.40-3.78, p = 0.001). Our findings suggest that a sub-classification of pT3 rectal cancer, based on the depth of tumor invasion, should be considered to be introduced in the TNM staging system.

Impact of Adjuvant Chemoradiotherapy on Survival of Resected Pancreatic Adenocarcinoma Cancer: A Surveillance, Epidemiology and End Results (SEER) Analysis.

BackgroundThe benefits of postoperative adjuvant chemoradiotherapy (CRT) for pancreatic cancer remain controversial. The purpose of this study is to determine if adjuvant CRT can improve the overall survival of postoperative pancreatic cancer patients compared to adjuvant chemotherapy (CT).MethodsPatients with resected pancreas adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). Multivariate Cox regression was used to determine the factors related to survival rate. Selection bias was reduced to a minimum through propensity matching analysis. Subgroup analyses by clinical characteristics were performed.ResultsThis study identified 10,097 patients who received adjuvant CT (n = 5,454) or adjuvant CRT (n = 4,643). On multivariate analysis, age, sex, tumor size, site, grade, stage, T stage, and lymph node metastasis were independent risk factors for OS. The basic clinical characteristics were well balanced after propensity matching. After propensity matching, CRT can improve the survival rate compared with CT [median OS: 22 months vs 23 months (HR, 0.928; 95% CI, 0.881–0.977; P = 0.004)]. Subgroup analysis indicated that the survival benefit of adjuvant chemoradiotherapy was more significant in patients with female (HR, 0.860; 95% CI, 0.798–0.926; P = 0.005 for interaction) or T3 (HR, 0.905; 95% CI, 0.855–0.957; P = 0.04 for interaction) or lymph nodes positive (HR, 0.883; 95% CI, 0.832–0.938; P = 0.005 for interaction).ConclusionAdjuvant CRT was associated with improved survival compared with adjuvant CT in patients with resection of pancreatic ductal adenocarcinoma. The benefit was more significant in patients with female or T3 or lymph nodes positive.

Portal Vein Irradiation Stent Plus Chemoembolization versus External Radiotherapy Plus Chemoembolization in Hepatocellular Carcinoma with Portal Vein Tumour Thrombus: A Retrospective Study.

To compare the clinical outcomes of portal vein irradiation stent implantation (PVIS) plus transcatheter arterial chemoembolization (TACE) and radiotherapy (RT) plus TACE in hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT). Data from 79 patients with HCC complicated by PVTT treated with PVIS implantation plus TACE (n = 53) or treated with RT plus TACE (n = 26) were retrospectively analysed. The primary outcome measure was overall survival, and the secondary outcome was the stent patency period. HCC response and complications were evaluated. At a median follow-up of 14.3 (range, 1.2 ~60) months, the median OS was 13.1 (95% CI: 9.8 ~16.4) months in the PVIS plus TACE group compared to 8.0 (95% CI: 6.1 ~9.9) months in the RT plus TACE group (p = 0.021). Stent occlusion was observed in 11 patients with a median patency time of 8.5 (range, 2 ~22) months. Multivariate Cox regression analysis demonstrated that Vp4 PVTT (HR: 5.22; 95% CI: 1.74-15.74) and poor responseto therapy (HR: 4.89; 95% CI: 2.66-8.99) were independent risk factors for OS, whereas PVIS plus TACE treatment (HR: 0.32; 95% CI: 0.18-0.56) was related to better prognosis. None of the patients in the two groups had grade 3-4 complications. In conclusion, this retrospective study shows that PVIS plus TACE provides a significantly better survival outcome than RT plus TACE for HCC patients with PVTT.

High Endothelin Receptor Type A Expression as an Independent Prognostic Biomarker and Correlated with Immune Infiltrates in Stomach Adenocarcinoma.

BackgroundStomach adenocarcinoma (STAD) is the most common gastrointestinal cancer and is associated with high mortality worldwide. Endothelin receptor type A (EDNRA) is associated with guanine-nucleotide-binding (G) proteins and plays important roles in cellular processes and various diseases.PurposeTo investigate the prognosis value of EDNRA expression and its correlation with immune infiltrates in patients with STAD.MethodsThe association between clinical characteristics and EDNRA expression in STAD was analyzed using the Wilcoxon signed-rank test and logistic regression. The Kaplan–Meier plotter analysis and Cox regression were constructed to evaluate the influence of EDNRA on prognosis, and a receiver operating characteristic (ROC) curve and nomogram were constructed. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were conducted to analyze the correlation between EDNRA and immune infiltrates. In addition, Oncomine, TIMER databases and qRT-PCR of STAD cell lines were used to verify the EDNRA expression in STAD.ResultsOur results revealed that EDNRA expression was significantly higher in patients with STAD than normal gastric tissues, and the results have been confirmed by RT-qPCR. KM-plotter analysis revealed that patients with STAD had shorter OS, FP, and PPS (P<0.001). Multivariate Cox analysis further confirmed that high EDNRA expression was an independent risk factor for OS in patients with STAD. Moreover, other clinicopathologic features were related with worse prognosis in STAD, including age, lymph nodes metastases and primary outcome. More importantly, ROC analysis also confirmed the diagnostic value, and a prognostic nomogram involving age, T, M, N classification, pathologic stage, residual tumor and EDNRA was constructed. GSEA revealed that high EDNRA expression was correlated with immunoregulatory interactions between lymphoid and non lymphoid cells pathways, natural killer cell activation involved in immune response, interleukin 1 receptor binding and pathways in cancer, and ssGSEA showed that EDNRA is correlated with macrophages and NK cells.ConclusionCollectively, EDNRA can be an independent prognostic biomarker and correlated with immune infiltration in stomach adenocarcinoma.

The prognosis of gastric adenocarcinoma depends on the crosstalk between immune profiles and tumor genomic alterations.

4035 Background: Gastric adenocarcinoma (GAC) is with a complex microenvironment of tumor cells. A better understanding of the immune landscape of GACs may lead to the improved treatment strategies with ICIs. Methods: To determine whether the molecular characteristics can serve in prognostic stratification of GACs, tumor tissue and blood samples were collected from 231 GAC patients. The median follow-up time was 34 months. The TCR profile was determined by TCR-β CDR3 sequencing while mutation and gene expression profiles were determined by whole exon and whole transcriptome sequencing, respectively. Tumour-infiltrating immune cells were characterized using immunofluorescence (IF) staining. Results: The results showed the OS of patients with high levels of TCR clonality (TCR clonal expansion) was significantly improved compared with patients with low levels (HR = 1.80 and 2.22, p = 0.022 and 0.008, respectively) in the whole group and in the subgroup of patients with stages IB to III disease. Furthermore, low local clonality was an independent risk factor for OS (adjusted-HR = 1.68 and 1.95, p = 0.049 and 0.029, respectively). Thus, TCR clonal expansion in tumour tissue had a strong prognostic value for GAC patients, independent of clinicopathological factors. Based on whole exon and whole transcriptome sequencing, RNF43/FBXW7/ARID2 mutations and local TCR clonality jointly impacted prognosis (p &lt; 0.001), and functional changes in corresponding Wnt pathway/Notch pathway/SWI/SNF complex characterized a GAC subset with enhanced tumour immunogenicity and TCR clonal expansion. TCR CDR3 sequence similarity comparisons yielded clusters of TCR clones of likely similar functions. The most expansive TCR clusters negatively correlated with the percentage of subclonal mutations (Pearson r = -0.8183, p &lt; 0.001), indicating that tumors with less genomic heterogeneity might induce a greater immune response. By IF staining and mutual correlation analysis, only M1 macrophages showed a significant positive correlation with local TCR clonality for epithelia, stroma, and total cell counts. Tumors were categorized according to the density of M1 macrophages, M1 macrophage infiltrated subtype was associated with favorable OS (p = 0.040 and 0.043) and its combination with the local TCR clonality improved prognosis stratification (p &lt; 0.001). Finally, the scoring by local TCR clonality, RNF43/FBXW7/ARID2 mutations and M1 infiltration determined the best prognosis (p &lt; 0.001). Conclusions: TCR profiles were associated with genomic alterations and may serve as a prognostic biomarker for GACs. A multi-omic model including TCR profiles might produce an improved stratification for treatments and outcomes.

EIF6 promotes the malignant progression of human hepatocellular carcinoma via the mTOR signaling pathway

BackgroundEukaryotic translation initiation factor 6 (eIF6) has a crucial function in the maturation of 60S ribosomal subunits, and it controls the initiation of protein translation. Although emerging studies indicate that eIF6 is aberrantly expressed in various types of cancers, the functions and underlying molecular mechanisms of eIF6 in the pathological progression of hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the potential diagnostic and prognostic value of eIF6 in patients with HCC.MethodsHCC samples enrolled from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and our cohort were used to explore the role and mechanism of eIF6 in HCC. The diagnostic power of eIF6 was verified by receiver operating characteristic curve (ROC) analysis and its prognostic value was assessed by Kaplan–Meier analysis, and then related biological functions of eIF6 were determined in vitro and in vivo cancer models. In addition, potential molecular mechanism of eIF6 in HCC was unveiled by the gene set enrichment analysis and western blot assay.ResultsWe demonstrated that eIF6 expression was markedly increased in HCC, and elevated eIF6 expression correlated with pathological progression of HCC. Besides, eIF6 served as not only a new diagnostic biomarker but also an independent risk factor for OS in HCC patients. Functional studies indicated that the deletion of eIF6 displayed tumor-suppressor activity in HCC cells. Furthermore, we found that eIF6 could activate the mTOR-related signaling pathway and regulate the expression level of its target genes, such as CCND1, CDK4, CDK6, MYC, CASP3 and CTNNBL1, and these activities promoted proliferation and invasion of HCC cells.ConclusionsThe findings of this study provided a novel basis for understanding the potential role of eIF6 in promoting tumor growth and invasion, and exploited a promising strategy for improving diagnosis and prognosis of HCC.

Mutational Spectrum and Prognosis Analysis of AML Patients Based on High-Throughput Sequencing

To investigate the mutational spectrum and its prognostic significance in patients with acute myeloid leukemia (AML). The clinical data of 93 patients with newly diagnosed AML who underwent gene mutation detection by high-throughput sequencing (HTS) from March 2014 to April 2018 in our hospital was analyzed retrospectively. The distribution of mutant genes was summarized and the prognostic factors for intermediate-risk acute myeloid leukemia (IR-AML) were analyzed. Among 93 AML patients, 88.17% had at least one gene mutation, and 53.76% patients showed more than one recurrent genetic mutation. CEBPA showed the highest mutation frequency (20.4%), followed by ASXL1, TET2, NRAS, FLT3-ITD, NPM1, IDH2, DNMT3A, and their mutation frequency were higher than 10%. IDH1/2 and NPM1, ASXL1 and U2AF1, FLT3 and NPM1 often co-occured (P < 0.05). In the prognosis analysis of 57 patients with IR-AML, the IDH2 mutation related with poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). The prognosis analysis of IR-AML patients showed that age≥50 years, WBC >100×109/L, anemia, and CD22+ were independent risk factors for OS. Age≥50 years , WBC >100×109/L, anemia, CD34+, IDH2 mutation were independent risk factors for PFS. There are co-occurring mutation patterns between the mutated genes. IDH2 mutations relates with poor prognosis and possesses potential to be molecules for model of IR-AML prognostic stratification. Genetic testing based on HTS contributes to revealing the pathogenic mechanism of AML, and is significant for evaluating the prognosis of patients with AML.

Impact of Intraoperative Blood Loss on the Survival of Patients With Stage II/III Colorectal Cancer: A Multicenter Retrospective Study.

Resection of the primary lesion with radical lymph node dissection is the most promising treatment avenue for patients with cancer. On the other hand, these procedures often induce excessive intraoperative blood loss (IBL) and require perioperative blood transfusion. The influence of IBL on the long-term postoperative outcomes of patients with digestive cancer is controversial. We investigated the impact of IBL on survival and recurrence after curative surgery in patients with colorectal cancer (CRC) in a single study group. In total, 1,597 patients who underwent radical resection for CRC at three group hospitals between 2000 and 2019 were reviewed. Patients were classified into a group with high IBL (≥200 ml) or low IBL (<200 ml). The risk factors for disease-free (DFS) and overall (OS) survival were analyzed. A total of 489 and 1,108 patients were classified into the high and low IBL groups, respectively. The OS and DFS rates at 5 years after surgery were 89.3% and 63.4%, respectively, for the high IBL group and 96.9% and 77.8% for the low IBL group; these differences were statistically significantly (p<0.001). The multivariate analysis demonstrated that IBL was a significant independent risk factor for OS and DFS. The amount of IBL was associated with significant differences in the OS and DFS of patients with stage II/III CRC who received curative resection. The surgical procedure, surgical strategy, and perioperative care should be carefully planned to avoid causing IBL.

Positive vein groove margin does not affect survival in patients undergoing pancreatoduodenectomy for early stages of pancreatic ductal adenocarcinoma

Presenter: Manish Ahuja MBBS, DNB | University Hospitals Birmingham NHS Trust Background: The prognostic significance of portal/superior mesenteric vein (PV/SMV) groove involvement after pancreaticoduodenectomy (PPPD) for pancreatic ductal adenocarcinoma (PDAC) is controversial. Following adoption of the reporting guidelines by the Royal College of Pathologists (R1: tumour margin < 1mm), R1 reporting rates have increased which are considered to impact the overall survival. The aim of this study was to investigate the significance of R1 vein groove margin on overall (OS) and disease-free survival (DFS) after pancreaticoduodenectomy (PD) for early stage pancreatic ductal adenocarcinoma (PDAC). Methods: This is a single centre retrospective study including all resections performed for resectable and borderline with venous only involvement (BR-V) PDAC of the head and uncinate process over a 10-year period (2011-2020). Statistical investigation was performed with descriptive statistics and Kaplan Meier and univariate and multivariate Cox regression survival analysis. Results: Two hundred patients underwent PD for resectable (n = 117, 59%) or BR-V (n = 83, 41%) tumours. Vein resection was performed in 102 (51%) cases. Pathological staging of the tumours was pT1 11 (6%), pT2 122 (61%) and pT3 67 (33%) cases; and pN0 18 (9%) pN1 101 (51%) pN2 81 (40%) cases. Clear surgical margins were observed in 35 (17%) cases. In 34 (17%) cases the vein groove margin was the only positive margin reported (VG+). Median follow-up was 14 months (range: 1-83). OS was significantly better in cases with clear margins (p = 0.006) (Picture 1a). No difference in OS was identified between VG+ only patients and those with negative margins (p = 0.129) or those with multiple sites of margin positivity (p = 0.172). Cox regression analysis did not identify VG+ only margin as an independent predictor of OS (Table 1). In a multivariate model investigating the surgical margins separately, the posterior, SMA and pancreas transection margins, as well as perineural invasion and adjuvant chemotherapy were identified as independent predictors of OS. DFS was significantly better if surgical margins were clear (p = 0.014) (Picture 1b). A trend to worse DFS was identified in patients with VG+ margin only compared to those with negative margins (p = 0.058). No difference in DSF was observed between VG+ only patients and those with multiple sites of margin positivity (p = 0.608). Cox regression analysis did not identify VG+ only margin as an independent predictor of DFS (Table 1). In a multivariate model investigating the surgical margins separately, the SMA margin was the only margin along with adjuvant chemotherapy that independently predicted DFS. Conclusion: Vein groove margin positivity doesn’t affect OS but may affect DFS after PD in patients with resectable and BR-V PDAC. In contrast, the posterior and pancreas transection margins along with PNI were identified as independent risk factors for OS. The SMA margin and adjuvant chemotherapy were independent factors for both OS and DFS.