Assessment of Response to Chemotherapy in Pancreatic Cancer with Liver Metastasis: CT Texture as a Predictive Biomarker

In this paper, we assess changes in CT texture of metastatic liver lesions after treatment with chemotherapy in patients with pancreatic cancer and determine if texture parameters correlate with measured time to progression (TTP). This retrospective study included 110 patients with pancreatic cancer with liver metastasis, and mean, entropy, kurtosis, skewness, mean of positive pixels, and standard deviation (SD) values were extracted during texture analysis. Response assessment was also obtained by using RECIST 1.1, Choi and modified Choi criteria, respectively. The correlation of texture parameters and existing assessment criteria with TTP were evaluated using Kaplan-Meier and Cox regression analyses in the training cohort. Kaplan-Meier curves of the proportion of patients without disease progression were significantly different for several texture parameters, and were better than those for RECIST 1.1-, Choi-, and modified Choi-defined response (p < 0.05 vs. p = 0.398, p = 0.142, and p = 0.536, respectively). Cox regression analysis showed that percentage change in SD was an independent predictor of TTP (p = 0.016) and confirmed in the validation cohort (p = 0.019). In conclusion, CT texture parameters have the potential to become predictive imaging biomarkers for response evaluation in pancreatic cancer with liver metastasis.

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Identify Prognostic Factors and Establish a Risk Stratification Model to Predict Cancer-Specific Survival for Patients with Pancreatic Cancer Liver Metastasis: A Population-Based Study

10.21203/rs.3.rs-855925/v1 ◽

2021 ◽

Author(s):

Biyang Cao ◽

Chenchen Wu ◽

Letian Zhang ◽

Jing Wang

Keyword(s):

Pancreatic Cancer ◽

Prognostic Factors ◽

Liver Metastasis ◽

Classification System ◽

Cox Regression ◽

Risk Classification ◽

Prognostic Models ◽

Cancer Specific Survival ◽

Discriminative Ability ◽

Cox Regression Analysis

Abstract Background Pancreatic cancer liver metastasis (PCLM) is a commonly fatal disease, but there are few prognostic models for these entities. The purpose of this study is to investigate prognostic factors based on clinicopathological characteristics and establish a prognostic nomogram predicting the cancer-specific survival (CSS) for PCLM patients. Methods The characteristics of 6015 patients with PCLM between 2010 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Prognostic factors and nomogram predicting CSS were developed by Cox proportional hazard regression model. The predictive accuracy and discriminative ability of nomogram were assessed by concordance index (C-index), calibration curve, decision curve analyses (DCAs) and receiver operating characteristic (ROC) curve. Moreover, a risk classification system was built according to the cut-off values off the nomogram. Results Based on the univariate and multivariate Cox regression analysis, significant prognostic factors were identified and included to establish the nomogram for CSS. The median survival time (MST) for all patients is 4.0 months (95% confidence interval [CI]:3.8–4.2) and CSS at 6, 12 and 18 months was 34.12%, 15.63% and 7.83%, respectively. The C-index of nomogram was 0.693 (95%CI: 0.689–0.697) and all verification results showed an accurate and discriminative ability in predicting CSS. Significant differences in Kaplan–Meier curves were observed in patients stratified into different risk groups (p < 0.001), with MST of 7.0 months (95% CI: 6.7–7.3), 3.0 months (95% CI: 2.7–3.3), and 2.0 months (95% CI: 1.8–2.2), respectively. Conclusions A prognostic nomogram and corresponding risk classification system were proposed to predict CSS for PCLM.

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IMUP and GPRC5A: Two Newly Identified Risk Score Indicators in Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-895660/v1 ◽

2021 ◽

Author(s):

Rong Wei ◽

Zixin Zeng ◽

Ningning Shen ◽

Ziyue Wang ◽

Honghong Shen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Cells ◽

Cox Regression ◽

Bioinformatic Analysis ◽

Cancer Development ◽

Local Hospital ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Key Genes ◽

The Difference

Abstract Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan-Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over 8-fold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the >8-fold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan-Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 64 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

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Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

Clinical Medicine Insights Oncology ◽

10.1177/1179554917728040 ◽

2017 ◽

Vol 11 ◽

pp. 117955491772804 ◽

Cited By ~ 5

Author(s):

Mridula Krishnan ◽

Aabra Ahmed ◽

Ryan W Walters ◽

Peter T Silberstein

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Survival Benefit ◽

Cox Regression ◽

Stage Iii ◽

National Cancer Database ◽

Factors Affecting ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Charlson Comorbidity Score

Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB) who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

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IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma

Cancer Cell International ◽

10.1186/s12935-021-02324-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rong Wei ◽

Guoye Qi ◽

Zixin Zeng ◽

Ningning Shen ◽

Ziyue Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Cells ◽

Cox Regression ◽

Bioinformatic Analysis ◽

Cancer Development ◽

Local Hospital ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Key Genes ◽

The Difference

Abstract Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan–Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan–Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

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Development of a Gene Risk Signature for Patients of Pancreatic Cancer

Journal of Healthcare Engineering ◽

10.1155/2022/4136825 ◽

2022 ◽

Vol 2022 ◽

pp. 1-8

Author(s):

Tao Liu ◽

Long Chen ◽

Guili Gao ◽

Xing Liang ◽

Junfeng Peng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Regression Analysis ◽

Cox Regression ◽

Roc Curves ◽

Cancer Prognosis ◽

Cox Regression Analysis ◽

Clinical Biomarkers ◽

Kaplan Meier ◽

Malignant Solid Tumor ◽

Patient Prognosis

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

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Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

Biomarkers in Medicine ◽

10.2217/bmm-2020-0141 ◽

2020 ◽

Vol 14 (12) ◽

pp. 1127-1137

Author(s):

Tong-Tong Zhang ◽

Yi-Qing Zhu ◽

Hong-Qing Cai ◽

Jun-Wen Zheng ◽

Jia-Jie Hao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Stage Ii ◽

Poor Prognostic Factor ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

BioMed Research International ◽

10.1155/2014/526932 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Cheng-Jui Lin ◽

Chi-Feng Pan ◽

Chih-Kuang Chuang ◽

Fang-Ju Sun ◽

Duen-Jen Wang ◽

...

Keyword(s):

Clinical Outcomes ◽

Cardiovascular Event ◽

Cox Regression ◽

Medical Center ◽

Serum Biochemistry ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Valuable Marker ◽

Valuable Predictor

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study.Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up.Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12,P=0.01), cardiovascular disease history (HR: 6.28,P=0.02), and PCS (HR: 1.12,P=0.02) were independently associated with cardiovascular event; age (HR: 0.91,P<0.01), serum albumin (HR: 0.03,P<0.01), and PCS level (HR: 1.17,P<0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rankP=0.03, log rankP<0.01, resp.).Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.

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Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0925 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Yoshida ◽

A Shibata ◽

A Tanihata ◽

H Hayashi ◽

Y Ichikawa ◽

...

Keyword(s):

Adverse Events ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Intramuscular Fat ◽

Left Ventricular ◽

Skeletal Muscle Atrophy ◽

Measured Quantity ◽

Ectopic Fat ◽

Cox Regression Analysis ◽

Kaplan Meier

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p<0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004). Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

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One-year outcomes of drug-coated balloon treatment for long femoropopliteal lesions: a multicentre cohort and real-world study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02127-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaoxi Yu ◽

Xin Zhang ◽

Zhichao Lai ◽

Jiang Shao ◽

Rong Zeng ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

Ankle Brachial Index ◽

Primary Patency ◽

Critical Limb Ischaemia ◽

Limb Ischaemia ◽

Cox Regression Analysis ◽

Femoropopliteal Artery ◽

Kaplan Meier ◽

Multicentre Cohort

Abstract Background Drug-coated balloons (DCBs) have shown superiority in the endovascular treatment of short femoropopliteal artery disease. Few studies have focused on outcomes in long lesions. This study aimed to evaluate the safety and effectiveness of Orchid® DCBs in long lesions over 1 year of follow-up. Methods This study is a multicentre cohort and real-world study. The patients had lesions longer than or equal to 150 mm of the femoropopliteal artery and were revascularized with DCBs. The primary endpoints were primary patency, freedom from clinically driven target lesion revascularization (TLR) at 12 months and major adverse events (all-cause death and major target limb amputation). The secondary endpoints were the changes in Rutherford classification and the ankle brachial index (ABI). Results One hundred fifteen lesions in 109 patients (mean age 67 ± 11 years, male proportion 71.6%) were included in this study. The mean lesion length was 252.3 ± 55.4 mm, and 78.3% of the lesions were chronic total occlusion (CTO). Primary patency by Kaplan–Meier estimation was 98.1% at 6 months and 82.1% at 12 months. The rate of freedom from TLR by Kaplan–Meier estimation was 88.4% through 12 months. There were no procedure- or device-related deaths through 12 months. The rate of all-cause death was 2.8%. Cox regression analysis suggested that renal failure and critical limb ischaemia (CLI) were statistically significant predictors of the primary patency endpoint. Conclusion In our real-world study, DCBs were safe and effective when used in long femoropopliteal lesions, and the primary patency rate at 12 months by Kaplan–Meier estimation was 82.1%.

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Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

Cancer Cell International ◽

10.1186/s12935-021-01756-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaoqing Luo ◽

Shunli Peng ◽

Sijie Ding ◽

Qin Zeng ◽

Rong Wang ◽

...

Keyword(s):

Lung Cancer ◽

Immune Checkpoint ◽

Cox Regression ◽

Tissue Array ◽

Lung Cancers ◽

Cox Regression Analysis ◽

Immune Checkpoint Molecules ◽

Cerna Network ◽

Kaplan Meier ◽

Infiltration Models

Abstract Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

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