Dataset Information

A Systematic Inflammation-based Model in Advanced Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Emerging evidence revealed the critical role of systematic inflammation in pancreatic ductal adenocarcinoma (PDAC). In the present study, we reviewed the records of 279 patients with advanced PDAC. Among them, 147 cases were used as the training cohort and another 132 as the validation cohort. In the training cohort, distant metastasis, carbohydrate antigen 19-9 (CA19-9), Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent prognostic factors in Cox regression. A nomogram based on these factors was generated to predict median survival time and survival probabilities at 6, 12, and 18 months. The nomogram showed a better discriminatory ability than the American Joint Committee on Cancer (AJCC) TNM staging (C-index: 0.727 vs. 0.610). In the validation cohort, a nomogram composed of the same variables also showed a high discriminatory ability (C-index: 0.784). In the low-risk group with a nomogram total point (NTP) value of more than 175, patients receiving combination therapy showed better prognosis than those receiving monotherapy (P=0.015). In conclusion, the nomogram based on inflammatory biomarkers can serve as useful prognostic tool for advanced PDAC. In addition, patients with high NTP can greater benefit from combination chemotherapy than monotherapy.

SUBMITTER: Wu LX

PROVIDER: S-EPMC6856880 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Systematic Inflammation-based Model in Advanced Pancreatic Ductal Adenocarcinoma.

Wu Li-Xia LX Wang Xiao-Yong XY Xu Ke-Qun KQ Lin Yu-Li YL Zhu Wen-Yu WY Han Long L Shao Yue-Ting YT Zhou Han-Yu HY Jiang Hua H Hang Jun-Jie JJ Yang Xu-Guang XG

Journal of Cancer 20191022 26

Emerging evidence revealed the critical role of systematic inflammation in pancreatic ductal adenocarcinoma (PDAC). In the present study, we reviewed the records of 279 patients with advanced PDAC. Among them, 147 cases were used as the training cohort and another 132 as the validation cohort. In the training cohort, distant metastasis, carbohydrate antigen 19-9 (CA19-9), Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were independent ...[more]

PMID: 31777596

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Project description:IntroductionPancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all solid tumors. Tumorigenesis is promoted by the oncogene KRAS, and KRAS mutations are prevalent in patients with PDAC. Therefore, a comprehensive understanding of the interactions between KRAS mutations and PDAC may expediate the development of therapeutic strategies for reversing the progression of malignant tumors. Our study aims at establishing and validating a prediction model of KRAS mutations in patients with PDAC based on survival analysis and mRNA expression.MethodsA total of 184 and 412 patients with PDAC from The Cancer Genome Atlas (TCGA) database and the International Cancer Genome Consortium (ICGC), respectively, were included in the study.ResultsAfter tumor mutation profile and copy number variation (CNV) analyses, we established and validated a prediction model of KRAS mutations, based on survival analysis and mRNA expression, that contained seven genes: CSTF2, FAF2, KIF20B, AKR1A1, APOM, KRT6C, and CD70. We confirmed that the model has a good predictive ability for the prognosis of overall survival (OS) in patients with KRAS-mutated PDAC. Then, we analyzed differential biological pathways, especially the ferroptosis pathway, through principal component analysis, pathway enrichment analysis, Gene Ontology (GO) enrichment analysis, and gene set enrichment analysis (GSEA), with which patients were classified into low- or high-risk groups. Pathway enrichment results revealed enrichment in the cytokine-cytokine receptor interaction, metabolism of xenobiotics by cytochrome P450, and viral protein interaction with cytokine and cytokine receptor pathways. Most of the enriched pathways are metabolic pathways predominantly enriched by downregulated genes, suggesting numerous downregulated metabolic pathways in the high-risk group. Subsequent tumor immune infiltration analysis indicated that neutrophil infiltration, resting CD4 memory T cells, and resting natural killer (NK) cells correlated with the risk score. After verifying that the seven gene expression levels in different KRAS-mutated pancreatic cancer cell lines were similar to that in the model, we screened potential drugs related to the risk score.DiscussionThis study established, analyzed, and validated a model for predicting the prognosis of PDAC based on risk stratification according to KRAS mutations, and identified differential pathways and highly effective drugs.

Dataset Information

A Systematic Inflammation-based Model in Advanced Pancreatic Ductal Adenocarcinoma.

Publications

A Systematic Inflammation-based Model in Advanced Pancreatic Ductal Adenocarcinoma.

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