scholarly journals An Integrated Nomogram Combining Clinical Factors and Microtubule-Associated Protein 1 Light Chain 3B Expression to Predict Postoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma

2020 ◽  
Vol 52 (2) ◽  
pp. 469-480 ◽  
Author(s):  
Liang Chen ◽  
Hongyuan Fu ◽  
Tongyu Lu ◽  
Jianye Cai ◽  
Wei Liu ◽  
...  
Keyword(s):  
Light Chain ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Clinical Information ◽  
Cancer Antigen 125 ◽  
Curative Intent ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Effective Models

PurposeMicrotubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy.Materials and MethodsFrom August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the Third Affiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolled patients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry.ResultsThe 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariate Cox regression analysis, independent risk factors for 5-year OS were cancer antigen 125, microvascular invasion, LC3B expression and lymph node metastasis. Except for the above 4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factors for 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and 0.747, respectively.ConclusionThe nomograms based on LC3B can be considered as effective models to predict postoperative survival for ICC patients.

Adjuvant chemotherapy following curative intent hepatectomy for intrahepatic cholangiocarcinoma: Results from a multi-institutional analysis of 575 patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4110-4110
Author(s):  
Dario Ribero ◽  
Antonio Daniele Pinna ◽  
Gennaro Nuzzo ◽  
Alfredo Guglielmi ◽  
Luca Aldrighetti ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Radical Resection ◽  
Continuous Variable ◽  
Outcome Data ◽  
Curative Intent ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cox Regression Analysis

4110 Background: Surgical resection alone is the standard of care for patients with resectable intrahepatic cholangiocarcinoma (IHC). This study evaluates the benefit of adjuvant chemotherapy (AdjCTx) following curative intent hepatectomy for IHC. Methods: Clinicopathologic and long-term outcome data of 575 consecutive patients treated with curative intent hepatectomy for IHC (1995-2011) were extracted from a multi-institutional registry. After excluding operative mortality and M1 (n=46), Cox regression analysis was used to identify independent determinants of early recurrence (i.e., within 3 years). Propensity scores, which are used in observational studies to reduce selection bias by equating groups on the basis of relevant covariates, were calculated and utilized to match patients who had or had not AdjCTx (one-to-one match). Cases whose propensity score deviated more than 0.10 were considered unmatched and excluded from the analysis. Primary end-point was recurrence-free survival (RFS) at 3-years. Results: At a median FU of 42 months, 247 patients had recurred. Predictors of recurrence were LN metastases (HR 1.83 [1.36-2.44]), radical resection (HR 0.64 [0.45-0.9]), an elevated preoperative CA19.9 (HR 1.54 [1.15-2.07]), vascular invasion (HR 1.97 [1.49-2.61]), multiple tumors (HR 2.21 [1.71-2.86]), and size (analysed as continuous variable) (HR 1.01 [1.01-1.01]). After matching, no difference was observed between patients who had or had not AdjCTx (n=155 per group; 3-yrs RFS 28.3% vs. 38.0%, respectively; p=NS). When the analysis was restricted to patients who had gemcitabine, GEMOX or FOLFOX for 3 or more cycles (n=64 per group) again no difference emerged between patients who had or had not AdjCTx (3-yrs RFS 27.7% vs. 40.0% respectively, p=NS ). Conclusions: Our data suggest that AdjCTx following resection of IHC does not increase 3-years RFS.

scholarly journals Prognostic Signatures of Alternative Splicing Events in Esophageal Carcinoma Based on TCGA Splice-Seq Data

2021 ◽  
Vol 11 ◽  
Author(s):  
Ping Ye ◽  
Yan Yang ◽  
Liqiang Zhang ◽  
Guixi Zheng
Keyword(s):  
Alternative Splicing ◽  
Esophageal Carcinoma ◽  
Cox Regression ◽  
Donor Site ◽  
Area Under The Curve ◽  
Clinical Information ◽  
Roc Curves ◽  
The Cancer Genome Atlas ◽  
Acceptor Site ◽  
Cox Regression Analysis

An alternative splicing (AS) event is a highly complex process that plays an essential role in post-transcriptional gene expression. Several studies have suggested that abnormal AS events were the primary element in the pathological process of cancer. However, few works are dedicated to the study of AS events in esophageal carcinoma (EC). In the present study, clinical information and RNA-seq data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The percent spliced in (PSI) values of AS events were acquired from the TCGA Splice-seq. A total of 183 EC patients were enrolled in this study, and 2,212 AS events were found significantly associated with the overall survival of these patients by univariate Cox regression analysis. The prognostic signatures based on AS events were built by multivariate Cox analysis. Receiver operating characteristic (ROC) curves displayed that the area under the curve (AUC) of the following prognostic signatures, including exon skip (ES), alternate terminator (AT), alternate acceptor site (AA), alternate promoter (AP), alternate donor site (AD), retained intron (RI), and total events, was greater than 0.8, suggesting that these seven signatures had valuable prognosis prediction capacity. Finally, the risk score of prognostic signatures was indicated as an independent risk factor of survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function of splicing factors (SFs) that were associated with AS events. Also, the interactive network between AS events and SFs identified several hub genes and AS events which need further study. This was a comprehensive study that explored prognosis-related AS events and established valuable prognosis signatures in EC patients. The network of interactions between AS events and SFs might offer novel insights into the fundamental mechanisms of tumorigenesis and progression of EC.

scholarly journals A Novel Clinical-Radiomics Model Based on Sarcopenia and Radiomics for Predicting the Prognosis of Intrahepatic Cholangiocarcinoma After Radical Hepatectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Liming Deng ◽  
Bo Chen ◽  
Chenyi Zhan ◽  
Haitao Yu ◽  
Jiuyi Zheng ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Psoas Muscle ◽  
Staging System ◽  
Predictive Performance ◽  
Arterial Phase ◽  
Neutrophil Lymphocyte Ratio ◽  
Staging Systems

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with a poor prognosis. This study aimed to establish a novel clinical-radiomics model for predicting the prognosis of ICC after radical hepatectomy.MethodsA clinical-radiomics model was established for 82 cases of ICC treated with radical hepatectomy in our hospital from May 2011 to December 2020. Radiomics features were extracted from venous-phase and arterial-phase images of computed tomography. Kaplan-Meier survival analysis was generated to compare overall survival (OS) between different groups. The independent factors were identified by univariate and multivariate Cox regression analyses. Nomogram performance was evaluated regarding discrimination, calibration, and clinical utility. C-index and area under the curve (AUC) were utilized to compare the predictive performance between the clinical-radiomics model and conventional staging systems.ResultsThe radiomics model included five features. The AUC of the radiomics model was 0.817 in the training cohort, and 0.684 in the validation cohort. The clinical-radiomics model included psoas muscle index, radiomics score, hepatolithiasis, carcinoembryonic antigen, and neutrophil/lymphocyte ratio. The reliable C-index of the model was 0.768, which was higher than that of other models. The AUC of the model for predicting OS at 1, and 3 years was 0.809 and 0.886, which was significantly higher than that of the American Joint Committee on Cancer 8th staging system (0.594 and 0.619), radiomics model (0.743 and 0.770), and tumor differentiation (0.645 and 0.628). After stratification according to the constructed model, the median OS was 59.8 months for low-risk ICC patients and 10.1 months for high-risk patients (p < 0.0001).ConclusionThe clinical-radiomics model integrating sarcopenia, clinical features, and radiomics score was accurate for prognostic prediction for mass-forming ICC patients. It provided an individualized prognostic evaluation in patients with mass-forming ICC and could helped surgeons with clinical decision-making.

scholarly journals Identification of a m6A RNA methylation regulators-based signature for predicting the prognosis of esophageal adenocarcinoma

2020 ◽  
Author(s):  
Yue Zhou ◽  
Shuyan Li ◽  
Liqing Zou ◽  
Tiantian Guo ◽  
Xi Yang ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Clustering Analysis ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract BackgroundN6-methyladenosine (m6A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. The aim of this study was to identify novel prognostic biomarkers by using m6A RNA methylation regulators capable of improving the risk-stratification criteria of survival for esophageal adenocarcinoma patients.MethodsThe gene expression data of 16 m6A methylation regulators and its relevant clinical information were extracted from The Cancer Genome Atlas (TCGA) database. The expression pattern of these m6A methylation regulators was evaluated. Consensus clustering analysis was conducted to identify clusters of esophageal adenocarcinoma patients with different prognosis. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct multiple-gene risk signature. A survival analysis was carried out to determine the prognosis significance.ResultsTen m6A methylation regulators (HNRNPA2B1, HNRNPC, YTHDF1, METTL3, YTHDF2, RBM15, YTHDC1, WTAP, KIAA1429 and YTHDF3) showed significant up-regulation in tumor tissue. Consensus clustering analysis identified three clusters of esophageal adenocarcinoma patients with different overall survival. A five-gene signature, HNRNPA2B1, KIAA1429, WTAP, METTL16 and ALKBH5, was constructed to serve as a prognostic indicator for distinguish esophageal adenocarcinoma patients with different prognosis. The receiver operator characteristic (ROC) curve which indicated the area under the curve (AUC) were 0.803, demonstrated that the prognostic signature had preferable prediction efficiency.Conclusionsm6A methylation regulators exert as potential biomarkers for prognostic stratification of esophageal adenocarcinoma patients and might help clinicians make individualized therapy for this patient population.

scholarly journals Preoperative Clinical and Computed Tomography (CT)-Based Nomogram to Predict Oncologic Outcomes in Patients with Pancreatic Head Cancer Resected with Curative Intent: A Retrospective Study

2019 ◽  
Vol 8 (10) ◽  
pp. 1749
Author(s):  
Shin Hye Hwang ◽  
Ha Yan Kim ◽  
Eun Ju Lee ◽  
Ho Kyoung Hwang ◽  
Mi-Suk Park ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cox Regression ◽  
Pancreatic Head ◽  
Clinical Information ◽  
Imaging Features ◽  
Curative Intent ◽  
Head Cancer ◽  
Cox Regression Analysis ◽  
Pancreatic Head Cancer ◽  
Preoperative Ct

Background: Currently, proposed nomograms are mainly based on post-operative histopathology. The purpose of this study was to identify preoperative computed tomography (CT) and clinical information that allow prediction of disease-free (DFS) and overall survival (OS) of patients surgically treated for pancreatic head cancer. Methods: A total of 136 patients who underwent curative-intent surgery were retrospectively reviewed. Based on results from multivariate Cox regression analysis, a prediction model was constructed with preoperative CT features and clinical information. Overall performance of the nomogram was calculated by Harrell’s C-index. Results: Symptoms at diagnosis, preoperative serum CA 19-9 ≥ 34 U/mL, and four imaging features (necrosis (DFS, P = 0.066; OS, P = 0.002), possible venous invasion (DFS, P = 0.150, OS, P = 0.055), suspected metastatic regional lymph node (DFS, P = 0.001; OS, P = 0.099), and associated pancreatitis or pseudocyst (DFS, P = 0.013; OS, P = 0.041)) were included to build the nomogram. The c-statistics for the discrimination power of the proposed nomogram was 0.6496 for DFS and 0.6746 for OS. Conclusion: A nomogram derived from preoperative CT and clinical information could estimate the risk of recurrence and all-cause death after curative-intent surgery for radiologically resectable pancreatic head cancer.

scholarly journals The prognostic and diagnostic significance of the neutrophil-to-lymphocyte ratio in hepatocellular carcinoma: a prospective controlled study

2021 ◽  
Author(s):  
Philip J. Johnson ◽  
Sofi Dhanaraj ◽  
Sarah Berhane ◽  
Laura Bonnett ◽  
Yuk Ting Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Models ◽  
Controlled Study ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

Abstract Background The neutrophil–lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC). Methods In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis. Results On entry into the study (‘baseline’), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage. Conclusion NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models.

scholarly journals Identification of prognostic alternative splicing events in sarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongshuai Li ◽  
Jie Yang ◽  
Guohui Yang ◽  
Jia Ren ◽  
Yu Meng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

scholarly journals The Presence of Small Nerve Fibers in the Tumor Microenvironment as Predictive Biomarker of Oncological Outcome Following Partial Hepatectomy for Intrahepatic Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3661
Author(s):  
Jan Bednarsch ◽  
Xiuxiang Tan ◽  
Zoltan Czigany ◽  
Dong Liu ◽  
Sven Arke Lang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Oncological Outcome ◽  
Nerve Fibers ◽  
Nodal Metastases ◽  
Cancer Specific Survival ◽  
Curative Intent ◽  
Term Outcome ◽  
Long Term Outcome

The oncological role of the density of nerve fibers (NFs) in the tumor microenvironment (TME) in intrahepatic cholangiocarcinoma (iCCA) remains to be determined. Therefore, data of 95 iCCA patients who underwent hepatectomy between 2010 and 2019 was analyzed regarding NFs and long-term outcome. Extensive group comparisons were carried out and the association of cancer-specific survival (CSS) and recurrence-free survival (RFS) with NFs were assessed using Cox regression models. Patients with iCCA and NFs showed a median CSS of 51 months (5-year-CSS = 47%) compared to 27 months (5-year-CSS = 21%) in patients without NFs (p = 0.043 log rank). Further, NFs (hazard ratio (HR) = 0.39, p = 0.002) and N-category (HR = 2.36, p = 0.010) were identified as independent predictors of CSS. Patients with NFs and without nodal metastases displayed a mean CSS of 89 months (5-year-CSS = 62%), while patients without NFs or with nodal metastases but not both showed a median CCS of 27 months (5-year-CSS = 25%) and patients with both positive lymph nodes and without NFs showed a median CCS of 10 months (5-year-CSS = 0%, p = 0.001 log rank). NFs in the TME are, therefore, a novel and important prognostic biomarker in iCCA patients. NFs alone and in combination with nodal status is suitable to identify iCCA patients at risk of poor oncological outcomes following curative-intent surgery.

scholarly journals Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alaa Rashad ◽  
Sherif Mousa ◽  
Hanaa Nafady-Hego ◽  
Asmaa Nafady ◽  
Hamed Elgendy
Keyword(s):  
Critically Ill ◽  
Cox Regression ◽  
Ferritin Level ◽  
Short Term ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Dexamethasone Group ◽  
Short Term Survival

AbstractTocilizumab (TCZ) and Dexamethasone are used for the treatment of critically ill COVID-19 patients. We compared the short-term survival of critically ill COVID-19 patients treated with either TCZ or Dexamethasone. 109 critically ill COVID-19 patients randomly assigned to either TCZ therapy (46 patients) or pulse Dexamethasone therapy (63 patients). Age, sex, neutrophil/ lymphocyte ratio, D-dimer, ferritin level, and CT chest pattern were comparable between groups. Kaplan–Meier survival analysis showed better survival in Dexamethasone group compared with TCZ (P = 0.002), patients didn’t need vasopressor at admission (P < 0.0001), patients on non-invasive ventilation compared to patients on mechanical ventilation (P<0.0001 ), and in patients with ground glass pattern in CT chest (P<0.0001 ) compared with those who have consolidation. Cox regression analysis showed that, TCZ therapy (HR = 2.162, 95% CI, 1.144–4.087, P <0.0001) compared with Dexamethasone group, higher neutrophil/Lymphocyte ratio (HR = 2.40, CI, 1.351–4.185, P = 0.003), lower PaO2/FiO2, 2 days after treatment, (HR = 1.147, 95% CI, 1.002–1.624, P < 0.0001) independently predicted higher probability of mortality. Dexamethasone showed better survival in severe COVID-19 compared to TCZ. Considering the risk factors mentioned here is crucial when dealing with severe COVID-19 cases.Clinical trial registration No clinicalTrials.gov: Nal protocol approved by Hospital Authorities, for data collection and for participation in CT04519385 (19/08/2020).

scholarly journals Prognostic Nomogram for Patients With Pancreatic Ductal Adenocarcinoma of Pancreatic Head After Pancreaticoduodenectomy

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Hongkai Zhuang ◽  
Zixuan Zhou ◽  
Zuyi Ma ◽  
Shanzhou Huang ◽  
Yuanfeng Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Cox Regression Analysis ◽  
Ajcc Stage

Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy. Methods: We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018. Results: Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model. Conclusions: A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.

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