Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study

Nahm, Christopher B.; Turchini, John; Jamieson, Nigel B.; Moon, Elizabeth; Sioson, Loretta; Itchins, Malinda; Arena, Jennifer; Colvin, Emily K.; Howell, Viive M.; Pavlakis, Nick; Clarke, Stephen; Samra, Jaswinder S.; Gill, Anthony J.; Mittal, Anubhav

doi:10.1016/j.ejso.2018.10.050

Cited by 26 publications

(18 citation statements)

References 21 publications

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“…Whole-tumor evaluation with magnetic resonance imaging (MRI) and texture analysis have established a model that predicts S100A4 overexpression as an imaging biomarker of PDAC (54). S100A4 can also be combined with other tumor biomarkers for early PC diagnosis and determination of PC prognosis (55)(56)(57)(58)(59), and the combinations can improve the accuracy of distinguishing PC from normal tissues to varying degrees. In conclusion, high S100A4 expression is not only a sign of pancreatic tumor malignancy but also a potential marker of PC metastasis and poor prognosis.…”

Section: S100a4: a Risk Factor For Pcmentioning

confidence: 99%

S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

Zhou

Guo

et al. 2021

Front. Oncol.

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Pancreatic cancer (PC) is a highly malignant tumor occurring in the digestive system. Currently, there is a lack of specific and effective interventions for PC; thus, further exploration regarding the pathogenesis of this malignancy is warranted. The S100 protein family, a collection of calcium-binding proteins expressed only in vertebrates, comprises 25 members with high sequence and structural similarity. Dysregulated expression of S100 proteins is a biomarker of cancer progression and prognosis. Functionally, these proteins are associated with the regulation of multiple cellular processes, including proliferation, apoptosis, growth, differentiation, enzyme activation, migration/invasion, Ca2+ homeostasis, and energy metabolism. This review highlights the significance of the S100 family in the diagnosis and prognosis of PC and its vital functions in tumor cell metastasis, invasion and proliferation. A further understanding of S100 proteins will provide potential therapeutic targets for preventing or treating PC.

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Section: S100a4: a Risk Factor For Pcmentioning

confidence: 99%

S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

Zhou

Guo

et al. 2021

Front. Oncol.

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“…It is frequently activated by gene mutation, amplification, or overexpression through abnormal regulation in human cancers. Among EGFR‐associated cancers, pancreatic adenocarcinoma (PAAD) has an extremely poor prognosis, which usually results in death within several months after diagnosis [11, 12]. In cancers like non‐small‐cell lung cancer (NSCLC) [13] and colon adenocarcinoma (COAD) [14], EGFR mutation status is considered as a poor prognostic factor, which is often associated with a more aggressive behavior and decreased patient survival.…”

Section: Introductionmentioning

confidence: 99%

“…However, successful applications of TKIs to other cancers are less certain [22]. Although many literature reports are available on EGFR mutation, overexpression, or amplification for particular cancer types [12‐14, 23, 24], a simultaneous comprehensive profiling over multiple cancer types to explore their similarity and difference is not available. Such information is important to understand what other cancers are more likely to benefit from such targeted therapy and what role EGFR plays among different cancers.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Liu

Zhang

Sun

2020

Cancer Communications

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Background Human epidermal growth factor receptor (EGFR) is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations. Although there are many reports for some individual cancers, comprehensive profiling of EGFR mutations, overexpression, amplification, DNA methylation, and their clinical associations across many different cancers simultaneously was not available. This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications. Methods The Cancer Genome Atlas (TCGA) datasets for 32 cancer types involving 11,314 patients were analyzed for alterations (mutations and amplification/deletion), abnormal expression and DNA methylation in EGFR gene. Mutation frequency, genomic location distribution, functional impact, and clinical targeted therapy implication were compared among different cancer types, and their associations with patient survival were analyzed. Results EGFR alteration frequency, mutation sites across functional domains, amplification, overexpression, and DNA methylation patterns differed greatly among different cancer types. The overall mutation frequency in all cancers combined was relatively low. Targetable mutations, mainly in lung cancer, were primarily found in the Pkinase_Tyr domain. Glioblastoma multiforme had the highest rate of alterations, but it was dominated by gene amplification and most mutations were in the Furin‐like domain where targeted therapy was less effective. Low‐grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome. Colon and pancreatic adenocarcinoma had very few EGFR mutations; however, high EGFR expression was significantly associated with short patient survival. Squamous cell carcinoma regardless of their sites (the head and neck, lung, or esophagus) exhibited similar characteristics with an alteration frequency of about 5.0%, was dominated by gene amplification, and had increased EGFR expression generally associated with short patient survival. DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers. Conclusions EGFR aberration type, frequency, distribution in functional domains, and expression vary from cancer to cancer. While mutations in the Pkinase_Tyr domain are more important for treatment selection, increased expression from amplification or deregulation affects more tumor types and leads to worse outcome, which calls for new treatment strategies for these EGFR‐driven tumors.

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“…A PDAC tissue biomarker panel (S100A4, Mesothelin, Ca-125) approach has recently been shown to be successful in prognosticating pancreatic cancer outcome (5). The expression of these biomarkers in the tumour tissue has been shown to track with the genetic changes associated with a more aggressive (so called 'squamous') genotype of PDAC (6).…”

Section: Introductionmentioning

confidence: 99%

Serum Biomarker Panel for Diagnosis and Prognosis of Pancreatic Ductal Adenocarcinomas

et al. 2021

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BackgroundPatients with pancreatic ductal adenocarcinoma (PDAC) have late diagnosis which results in poor prognosis. Currently, surgical resection is the only option for curative intent. Identifying high-risk features for patients with aggressive PDAC is essential for accurate diagnosis, prognostication, and personalised care due to the disease burden and risk of recurrence despite surgical resection. A panel of three biomarkers identified in tumour tissue (S100A4, Ca125 and Mesothelin) have shown an association with poor prognosis and overall survival. The diagnostic and prognostic value of the serum concentration of this particular biomarker panel for patients with PDAC has not been previously studied.MethodsRetrospectively collected blood samples of PDAC patients (n =120) and healthy controls (n =80) were evaluated for the serum concentration of select biomarkers – S100A4, S100A2, Ca-125, Ca 19-9 and mesothelin. Statistical analyses were performed for diagnostic and prognostic correlation.ResultsA panel of four biomarkers (S100A2, S100A4, Ca-125 and Ca 19-9) achieved high diagnostic potential (AUROC 0.913). Three biomarkers (S100A4, Ca-125 and Ca 19-9) correlated with poor overall survival in a univariable model (p < 0.05). PDAC patients with abnormal levels of 2 or more biomarkers in their serum demonstrated significantly lower survival compared to patients with abnormal levels of one or less biomarker (p < 0.05).Conclusion and ImpactThe identified biomarker panels have shown the potential to diagnose PDAC patients and stratify patients based on their prognostic outcomes. If independently validated, this may lead to the development of a diagnostic and prognosticating blood test for PDAC.

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Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: A multi-institutional cohort study

Cited by 26 publications

References 21 publications

S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Serum Biomarker Panel for Diagnosis and Prognosis of Pancreatic Ductal Adenocarcinomas

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