scholarly journals Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma

2021 ◽  
Vol 27 ◽  
Author(s):  
Yinlei Dong ◽  
Junjie Tian ◽  
Bingqian Yan ◽  
Kun Lv ◽  
Ji Li ◽  
...  

It is widely acknowledged that metastasis determines the prognosis of pancreatic adenocarcinoma (PAAD), and the liver is the most primary distant metastatic location of PAAD. It is worth exploring the value of liver-metastasis-related genetic prognostic signature (LM-PS) in predicting the clinical outcomes of PAAD patients post R0 resection. We collected 65 tumors and 165 normal pancreatic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx), respectively. Differentially expressed genes (DEGs) between primary tumor and normal pancreatic samples were intersected with DEGs between primary tumor samples with liver metastasis and those without new tumor events. The intersected 45 genes were input into univariate Cox regression analysis to identify the prognostic genes. Thirty-three prognostic liver-metastasis-related genes were identified and included in least absolute shrinkage and selection operator (LASSO) analysis to develop a seven-gene LM-PS, which included six risk genes (ANO1, FAM83A, GPR87, ITGB6, KLK10, and SERPINE1) and one protective gene (SMIM32). The PAAD patients were grouped into low- and high-risk groups based on the median value of risk scores. The LM-PS harbored an independent predictive ability to distinguish patients with a high-risk of death and liver metastasis after R0 resection. Moreover, a robust prognostic nomogram based on LM-PS, the number of positive lymph nodes, and histologic grade were established to predict the overall survival of PAAD patients. Besides, a transcription factor‐microRNA coregulatory network was constructed for the seven LM-PS genes, and the immune infiltration and genomic alterations were systematically explored in the TGCA-PAAD cohort.

2021 ◽  
Author(s):  
Yanyao Deng ◽  
Hai Hu ◽  
Le Xiao ◽  
Ting Cai ◽  
Wenzhe Gao ◽  
...  

Abstract Background: Epithelial-Mesenchymal Transition (EMT) can promote carcinoma progression by multiple mechanisms, many studies demonstrated the invasiveness of pancreatic adenocarcinoma (PAAD) associated with the EMT, but how it acts in a lncRNA dependent manner is unclear. Methods: We investigated 146 PAAD samples from The Cancer Genome Atlas (TCGA) and 92 samples from the International Cancer Genome Consortium (ICGC). Gene set variation analysis (GSVA) and weighted correlation network analysis (WGCNA) were applied to explore the EMT related long non-coding RNAs (EMTlnc). Univariate Cox regression analysis was performed to screen their prognostic roles in PAAD patients. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish an EMT-related lncRNA prognostic signature (EMT-LPS). We also established a competing endogenous RNA (ceRNA) network. Results: 33 prognostic EMTlnc were identified as prognostic lncRNAs and an EMT-LPS were established. We divided the patients into low- and high-risk subgroups according to corresponding risk scores. The EMT-LPS showed a powerful prognostic predicting ability in stratification analysis. Principal component analysis (PCA) showed the low- and high-risk subgroups had distinct EMT status. Enrichment analysis indicated malignancy correlated biological processes, pathways and hallmarks were more common in the high-risk subgroup. Moreover, we constructed a nomogram that had a strong ability to forecast the overall survival (OS) of the PAAD patients in both datasets. Conclusion: EMT-LPS are important factors in the carcinoma progression of PAAD and may help in decision making regarding the choice of prognosis assessment and provide us clues to design the new drugs for PAAD.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15688-e15688
Author(s):  
Nicholas Manguso ◽  
Attiya Harit ◽  
Nicholas N. Nissen ◽  
James Mirocha ◽  
Andrew Eugene Hendifar ◽  
...  

e15688 Background: Management of liver metastasis in patients with small bowel neuroendocrine tumors (SBNET) remains unclear. Complete surgical resection improves long term survival however factors that influence overall prognosis are not clear. Methods: Database review identified 301 patients diagnosed with SBNET from 1990 to 2013. Only patients with known liver metastasis who underwent resection of the primary tumor were included. Outcomes among patients who underwent complete surgical resection, incomplete debulking of liver metastasis, and resection of the primary tumor alone were compared. The Kaplan-Meier method was used for survival estimates and Cox regression was used to identify predictors of death. Results: 111 patients met study criteria. Median age was 59 years (range 16-80); 49% were male. The terminal ileum (47/111, 42%) was the most common primary tumor location. The median number of liver lesions was 8.5 (range 1-31) and median lesions resected was 1 (range 0-31). In addition to resection of the primary tumor, 36 patients (32%) had no liver resection (NR), 41 (36.9%) had complete resection of liver disease (R0) and 34 (30%) had incomplete resection of liver metastasis (R1). 58 patients (36%) had one or more wedge resections, 12 (10.8%) underwent segmentectomy and 5 (4.5%) had a lobectomy. 33 (29.7%) patients underwent post-operative chemoembolization, 25 (22.5%) had radioembolization and 23 (20.7%) had radiofrequency ablation. The R1 group differed from the R0 group in median size of primary tumor (2.5 cm R1 vs 1.6 cm R0, p = 0.05) and median number of positive lymph nodes (5.0 R1 vs 3.0 R0, p = 0.05). The 5-year OS was 80.9%, 81.1% and 100% for NR, R1 and R0 groups respectively (p = 0.01). 10-year OS did not differ between groups (72.8% NR vs 81.1% R1vs 82.5% NR, p = 0.31). Cox regression showed post-operative administration of chemotherapy (HR = 3.68, p < 0.01) and higher tumor grade (HR = 18.4, p = 0.02) increased risk of death. Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16760-e16760
Author(s):  
Moataz Ellithi ◽  
Mohamed A. Abdallah ◽  
Mahum Shahid ◽  
Isaak Ailts ◽  
Kate Waligoske ◽  
...  

e16760 Background: Pancreatic adenocarcinoma represents the fourth leading cause of cancer-related death in the United States. A majority of patients have locally advanced or metastatic disease at the time of diagnosis. For many years, gemcitabine monotherapy was the standard of care for advanced disease, until recent studies demonstrated survival benefits for FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and Gem/nab-P (gemcitabine/nab-paclitaxel). In this study, we evaluated the clinical outcomes in patients with metastatic pancreatic adenocarcinoma in a single health system before and after the incorporation of these newer treatments into practice. Methods: A retrospective study of metastatic pancreatic adenocarcinoma patients diagnosed between January 2009 to December 2018 with follow up until December 2019. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier survival analysis. Univariate and multivariable Cox regression analyses were used to explore predictors of survival. Results: 394 patients were diagnosed with metastatic pancreatic adenocarcinoma at Sanford Health hospitals during the study period. There was no statistically significant difference in OS between the cohort diagnosed between 2009-2013 compared to 2014-2018, with median OS of 4.7 and 3.6 months respectively; in those receiving at least one line of chemotherapy, the median OS was 6.7 and 7.3 months. While subgroup analysis of all study population based on the type of first-line chemotherapy showed improved survival with FOLFIRINOX and Gem/nabP as compared to gemcitabine monotherapy [10.7, 6.9, 4 months respectively] (Wilcoxon Test of Homogeneity of Survival Curves p = 0.0002). Univariate and multivariate Cox regression analysis of all study data revealed that at the time of the diagnosis, age (HR: 1.021, p = 0.0013), ECOG performance status > 1 (HR: 3.47, p = 0.0001), serum albumin (HR: 0.708, p = 0.0002), Neutrophil-to-Lymphocytes ratio (HR: 1.076, p≤0.0001) and platelets-to-lymphocyte ratio (HR: 0.998, p = 0.0031) were predictors of survival. Conclusions: Although newer treatments appear to offer improved survival for eligible patients, overall outcomes for metastatic pancreatic adenocarcinoma in this cohort were similar before and after the incorporation of newer treatment regimens. Further advances in the treatment and early detection of pancreatic cancer are needed to improve clinical outcomes.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Gang Xiao ◽  
Xuan Gao ◽  
Lifeng Li ◽  
Chao Liu ◽  
Zhiyuan Liu ◽  
...  

Background. IDH mutation is the most common in diffuse LGGs, correlated with a favorable prognosis. However, the IDH-mutant LGGs patients with poor prognoses need to be identified, and the potential mechanism leading to a worse outcome and treatment options needs to be investigated. Methods. A six-gene immune-related prognostic signature in IDH-mutant LGGs was constructed based on two public datasets and univariate, multivariate, and LASSO Cox regression analysis. Patients were divided into low- and high-risk groups based on the median risk score in the training and validation sets. We analyzed enriched pathways and immune cell infiltration, applying the GSEA and the immune evaluation algorithms. Results. Stratification and multivariate Cox analysis unveiled that the six-gene signature was an independent prognostic factor. The signature (0.806/0.795/0.822) showed a remarkable prognostic performance, with 1-, 3-, and 5-year time-dependent AUC, higher than for grade (0.612/0.638/0.649) and 1p19q codeletion status (0.606/0.658/0.676). High-risk patients had higher infiltrating immune cells. However, the specific immune escape was observed in the high-risk group after immune activation, owing to increasing immunosuppressive cells, inhibitory cytokines, and immune checkpoint molecules. Moreover, a novel nomogram model was developed to evaluate the survival in IDH-mutant LGGs patients. Conclusion. The six-gene signature could be a promising prognostic biomarker, which is promising to promote individual therapy and improve the clinical outcomes of IDH-mutant gliomas. The study also refined the current classification system of IDH-mutant gliomas, classifying patients into two subtypes with distinct immunophenotypes and overall survival.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Zhao ◽  
Rixiang Zhao ◽  
Xiaocen Wei ◽  
Xiaojing Jiang ◽  
Fan Su

Background. Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. Methods. In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan–Meier curve, a time-dependent receiver operating characteristic (ROC) curve. Results. After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide ( P = 0.0099 ) and mitomycin C ( P = 0.0013 ). Conclusion. It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.


Author(s):  
Gaoming Wang ◽  
Ludi Yang ◽  
Miao Hu ◽  
Renhao Hu ◽  
Yongkun Wang ◽  
...  

Stomach adenocarcinoma (STAD) is one of the most common cancers in the world. However, the prognosis of STAD remains poor, and the therapeutic effect of chemotherapy and immunotherapy varies from person to person. MicroRNAs (miRNAs) play vital roles in tumor development and metastasis and can be used for cancer diagnosis and prognosis. In this study, hsa-miR-100-5p was identified as the only dysregulated miRNA in STAD samples through an analysis of three miRNA expression matrices. A weighted gene co-expression network analysis (WGCNA) was performed to select hsa-miR-100-5p-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a miR-100-5p-related prognostic signature. Kaplan–Meier analyses, nomograms, and univariate and multivariate Cox regression analyses were used to evaluate the prognostic signature, which was subsequently identified as an independent risk factor for STAD patients. We investigated the tumor immune environment between low- and high-risk groups and found that, among component types, M2 macrophages contributed the most to the difference between these groups. A drug sensitivity analysis suggested that patients with high-risk scores may be more sensitive to docetaxel and cisplatin chemotherapy and that patients in the low-risk group may be more likely to benefit from immunotherapy. Finally, external cohorts were evaluated to validate the robustness of the prognostic signature. In summary, this study may provide new ideas for developing more individualized therapeutic strategies for STAD patients.


2020 ◽  
Author(s):  
Gang Wang ◽  
Ling Wen Wang ◽  
Jie Hai Jin ◽  
min Hong Dong ◽  
wei Wei Chen ◽  
...  

Abstract Background: To evaluate the impact of primary tumor radiotherapy on survival in patients with unresectable metastatic rectal or rectosigmoid cancer. Methods: Form September 2008 to September 2017, 350 patients with unresectable metastatic rectal or rectosigmoid cancer were retrospectively reviewed in our center. All patients received at least 4 cycles of chemotherapy, and were divided into two groups according to with primary tumor radiotherapy or without. 163 patients received primary tumor radiotherapy, and the median radiation dose was 56.69Gy(50.4-60). Survival curves were estimated from the Kaplan–Meier procedure to roughly compare survival among two groups. Subsequently, 18-month survival was used as the outcome variable for this study. This study mainly evaluated the impact of primary tumor radiotherapy on survival of these patients through a series of multivariate Cox regression analyses after propensity score matching (PSM). Results: The median follow-up time was 21 months. All 350 patients received a median of 7 cycles of chemotherapy (range 4-12), 163 (46.67%) patients received primary tumor radiotherapy for local symptoms. The Kaplan–Meier survival curves showed a significant overall survival (OS) advantage for primary tumor radiotherapy group to without radiotherapy (20.07 vs 17.33 months; P=0.002). In this study, multivariate Cox regression analysis after adjusted covariates, multivariate Cox regression analysis after PSM, and inverse probability of treatment weighting (IPTW) analysis and propensity score (PS)-adjusted model analysis consistently showed that primary tumor radiotherapy could effectively reduce the risk of death for these patients at 18 months (HR: 0.62, 95% CI 0.40-0.98; HR:0.79, 95% CI:0.93-1.45; HR: 0.70, 95% CI 0.55-0.99 and HR: 0.74, 95% CI:0.59-0.94). Conclusion: Compared with patients with stage IV rectal or rectosigmoid cancer who did not receive primary tumor radiotherapy, received primary tumor radiotherapy reduced the risk of death in these patients. The radical doses(59.4Gy/ 33 fractions or 60Gy/ 30 fractions) of radiation for primary tumors might be considered for unresectable metastatic rectal or rectosigmoid cancer, not just for relieve symptoms. Keywords: Stage IV Rectal cancer, primary tumor radiotherapy, propensity score matching.


2021 ◽  
Author(s):  
Shaomei Tang ◽  
Xiaoliang Huang ◽  
Haixing Jiang ◽  
Shanyu Qin

Abstract Background: Pancreatic adenocarcinoma (PAAD) is an extremely malignant cancer. Immunotherapy is a promising avenue for elevating survival time of PAAD patients.Methods: The RNA sequencing and clinical data of PAAD were downloaded from the TCGA database. The ssGSEA method and weighted gene co-expression network analysis were used to calculate the relative abundance of tumor-infiltrated immune cells and identified the immune cells closely related module. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were used to construct a prognostic model. MCPcounter and EPIC were also applied to assess the immune cell components using gene expression profile.Results: The B cells closely related module was identified and five genes including ARID5A, CLEC2B, MICAL1, MZB1 and RAPGEF1 were ultimately selected to establish the prognostic signature for calculating risk scores of PAAD patients. Kaplan-Meier curves presented a worse survival in the high-risk patients (p<0.05) and the area under the Receiver operating characteristic (ROC) curve of risk score for 1-year and 3-year survival were 0.78 and 0.80 based on the training set. Also, similar results were verified in the validated and combined sets. Interestingly, low-risk group presented significantly elevated immune, stroma scores and proportion of B cells and associations between these five genes and B cells were identified by using multiple methods including ssGSEA, MCPcounter and EPIC. Conclusions: This is the first attempt to study a B cells related prognostic signature, which is instrumental in exploration of novel prognostic biomarkers in PAAD.


2021 ◽  
Vol 19 (12) ◽  
pp. 1425-1432
Author(s):  
Kan Wu ◽  
Xu Liu ◽  
Zhihong Liu ◽  
Yiping Lu ◽  
Xianding Wang ◽  
...  

Background: Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC. Patients and Methods: All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004–2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival. Results: Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29–0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559). Conclusions: Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.


2021 ◽  
Vol 8 ◽  
Author(s):  
Chunpeng Sheng ◽  
Zhihua Chen ◽  
Jianwei Lei ◽  
Jianming Zhu ◽  
Shuxin Song

Objective: Increasing evidence emphasizes the clinical implications of RNA binding proteins (RBPs) in cancers. This study aimed to develop a RBP signature for predicting prognosis in glioma.Methods: Two glioma datasets as training (n = 693) and validation (n = 325) sets were retrieved from the CGGA database. In the training set, univariate Cox regression analysis was conducted to screen prognosis-related RBPs based on differentially expressed RBPs between WHO grade II and IV. A ten-RBP signature was then established. The predictive efficacy was evaluated by ROCs. The applicability was verified in the validation set. The pathways involving the risk scores were analyzed by ssGSEA. scRNA-seq was utilized for evaluating their expression in different glioma cell types. Moreover, their expression was externally validated between glioma and control samples.Results: Based on 39 prognosis-related RBPs, a ten RBP signature was constructed. High risk score distinctly indicated a poorer prognosis than low risk score. AUCs were separately 0.838 and 0.822 in the training and validation sets, suggesting its well performance for prognosis prediction. Following adjustment of other clinicopathological characteristics, the signature was an independent risk factor. Various cancer-related pathways were significantly activated in samples with high risk score. The scRNA-seq identified that risk RBPs were mainly expressed in glioma malignant cells. Their high expression was also found in glioma than control samples.Conclusion: This study developed a novel RBP signature for robustly predicting prognosis of glioma following multi-data set verification. These RBPs may affect the progression of glioma.


Sign in / Sign up

Export Citation Format

Share Document