Dataset Information

Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma.

ABSTRACT:

Background

RNA-sequencing-based classifiers can stratify pancreatic ductal adenocarcinoma (PDAC) into prognostically significant subgroups but are not practical for use in clinical workflows. Here, we assess whether histomorphological features may be used as surrogate markers for predicting molecular subgroup and overall survival in PDAC.

Methods

Ninety-six tissue samples from 50 patients with non-resectable PDAC were scored for gland formation, stromal maturity, mucin, necrosis, and neutrophil infiltration. Prognostic PDAC gene expression classifiers were run on all tumors using whole transcriptome sequencing data from the POG trial (NCT02155621). Findings were validated using digital TCGA slides (n = 50). Survival analysis used multivariate Cox proportional-hazards tests and log-rank tests.

Results

The combination of low gland formation and low neutrophil infiltration was significantly associated with the poor prognosis PDAC molecular subgroup (basal-like or squamous) and was an independent predictor of shorter overall survival, in both frozen section (n = 47) and formalin-fixed paraffin-embedded (n = 49) tissue samples from POG patients, and in the TCGA samples. This finding held true in the subgroup analysis of primary (n = 17) and metastatic samples (n = 79). The combination of high gland formation and high neutrophils had low sensitivity but high specificity for favorable prognosis subgroups.

Conclusions

The assessment of gland formation and neutrophil infiltration on routine histological sections can aid in prognostication and allow inferences to be made about molecular subtype, which may help guide patient management decisions and contribute to our understanding of heterogeneity in treatment response.

SUBMITTER: Naso JR

PROVIDER: S-EPMC7897949 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma.

Naso Julia R JR Topham James T JT Karasinska Joanna M JM Lee Michael K C MKC Kalloger Steve E SE Wong Hui-Li HL Nelson Jessica J Moore Richard A RA Mungall Andrew J AJ Jones Steven J M SJM Laskin Janessa J Marra Marco A MA Renouf Daniel J DJ Schaeffer David F DF

Cancer medicine 20201228 3

<h4>Background</h4>RNA-sequencing-based classifiers can stratify pancreatic ductal adenocarcinoma (PDAC) into prognostically significant subgroups but are not practical for use in clinical workflows. Here, we assess whether histomorphological features may be used as surrogate markers for predicting molecular subgroup and overall survival in PDAC.<h4>Methods</h4>Ninety-six tissue samples from 50 patients with non-resectable PDAC were scored for gland formation, stromal maturity, mucin, necrosis, ...[more]

PMID: 33372414

Similar Datasets

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection.MethodsWe performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n = 70) PDAC cohort to verify the conclusion.ResultsBoth the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p = 0.011 and p = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p = 0.017) and 1.596 (95% CI: 1.061-2.401, p = 0.025), respectively.ConclusionsMUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death.

Dataset Information

Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma.

Similar Datasets

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