Current Pathology Model of Pancreatic Cancer

Szymoński, K; Milian-Ciesielska, Katarzyna; Lipiec, Ewelina; Adamek, Dariusz

doi:10.3390/cancers14092321

Cited by 10 publications

(19 citation statements)

References 255 publications

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“…When designing studies based on PC diagnosis, one must differentiate the results concerning the histomorphological type of the tumor. This distinction is crucial for patient care, due to different molecular pathways governing the development and evolution of these tumors, as well as the prognosis assessment and potential treatment options[ 3 ]. In our previous study, we demonstrated that Raman spectroscopy (RS) is capable of detecting ampullary cancer in pancreatic tumor tissue slides[ 34 ].…”

Section: Pdac Heterogeneity and Chemoresistancementioning

confidence: 99%

“…Another prognostically relevant, yet complex factor is related to the morphological and molecular heterogeneity of the tumor cells and the surrounding stroma. On one hand, the need for proper pathological evaluation with a detailed prognostic assessment is required, on the other, more importantly, the variability of PC leads to chemoresistance[ 3 ]. Moreover, differentiating PC from large tumors of the ampulla of Vater remains challenging[ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, differentiating PC from large tumors of the ampulla of Vater remains challenging[ 4 ]. Our previous article highlighted recent trends in PC pathology and research[ 3 ]. Vibrational spectroscopy (VS)-based methods will play prominent roles in the early diagnosis of PC (Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

“… Main trends in pancreatic cancer pathology and research aim to improve survival[ 3 ]. Poor pancreatic ductal adenocarcinoma (PDAC) prognosis for a patient is multifactorial, and the lack of sensitive and specific early diagnostic methods is one of the reasons.…”

Section: Introductionmentioning

confidence: 99%

“…Detailed pathological reporting is crucial for targeted and personalized therapy. The development of new diagnostic methods, combined with a proper pathologic evaluation and spectroscopic profiling, lead to effective treatment and supposedly will increase PDAC patients’ survival rates; Adapted with permission from[ 3 ]. Citation: Szymoński K, Milian-Ciesielska K, Lipiec E, Adamek D. Current Pathology Model of Pancreatic Cancer.…”

Section: Introductionmentioning

confidence: 99%

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Vibrational spectroscopy – are we close to finding a solution for early pancreatic cancer diagnosis?

Szymoński¹,

Chmura²,

Lipiec³

et al. 2023

World J Gastroenterol

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Pancreatic cancer (PC) is an aggressive and lethal neoplasm, ranking seventh in the world for cancer deaths, with an overall 5-year survival rate of below 10%. The knowledge about PC pathogenesis is rapidly expanding. New aspects of tumor biology, including its molecular and morphological heterogeneity, have been reported to explain the complicated “cross-talk” that occurs between the cancer cells and the tumor stroma or the nature of pancreatic ductal adenocarcinoma-associated neural remodeling. Nevertheless, currently, there are no specific and sensitive diagnosis options for PC. Vibrational spectroscopy (VS) shows a promising role in the development of early diagnosis technology. In this review, we summarize recent reports about improvements in spectroscopic methodologies, briefly explain and highlight the drawbacks of each of them, and discuss available solutions. The important aspects of spectroscopic data evaluation with multivariate analysis and a convolutional neural network methodology are depicted. We conclude by presenting a study design for systemic verification of the VS-based methods in the diagnosis of PC.

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Section: Pdac Heterogeneity and Chemoresistancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Vibrational spectroscopy – are we close to finding a solution for early pancreatic cancer diagnosis?

Szymoński¹,

Chmura²,

Lipiec³

et al. 2023

World J Gastroenterol

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Combined analytical approach empowers precise spectroscopic interpretation of subcellular components of pancreatic cancer cells

Szymoński,

Skirlińska-Nosek,

Lipiec

et al. 2023

Anal Bioanal Chem

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The lack of specific and sensitive early diagnostic options for pancreatic cancer (PC) results in patients being largely diagnosed with late-stage disease, thus inoperable and burdened with high mortality. Molecular spectroscopic methodologies, such as Raman or infrared spectroscopies, show promise in becoming a leader in screening for early-stage cancer diseases, including PC. However, should such technology be introduced, the identification of differentiating spectral features between various cancer types is required. This would not be possible without the precise extraction of spectra without the contamination by necrosis, inflammation, desmoplasia, or extracellular fluids such as mucous that surround tumor cells. Moreover, an efficient methodology for their interpretation has not been well defined. In this study, we compared different methods of spectral analysis to find the best for investigating the biomolecular composition of PC cells cytoplasm and nuclei separately. Sixteen PC tissue samples of main PC subtypes (ductal adenocarcinoma, intraductal papillary mucinous carcinoma, and ampulla of Vater carcinoma) were collected with Raman hyperspectral mapping, resulting in 191,355 Raman spectra and analyzed with comparative methodologies, specifically, hierarchical cluster analysis, non-negative matrix factorization, T-distributed stochastic neighbor embedding, principal components analysis (PCA), and convolutional neural networks (CNN). As a result, we propose an innovative approach to spectra classification by CNN, combined with PCA for molecular characterization. The CNN-based spectra classification achieved over 98% successful validation rate. Subsequent analyses of spectral features revealed differences among PC subtypes and between the cytoplasm and nuclei of their cells. Our study establishes an optimal methodology for cancer tissue spectral data classification and interpretation that allows precise and cognitive studies of cancer cells and their subcellular components, without mixing the results with cancer-surrounding tissue. As a proof of concept, we describe findings that add to the spectroscopic understanding of PC. Graphical Abstract

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Variabilities in global DNA methylation and β-sheet richness establish spectroscopic landscapes among subtypes of pancreatic cancer

Szymoński

Lipiec²,

Sofińska³

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose Knowledge about pancreatic cancer (PC) biology has been growing rapidly in recent decades. Nevertheless, the survival of PC patients has not greatly improved. The development of a novel methodology suitable for deep investigation of the nature of PC tumors is of great importance. Molecular imaging techniques, such as Fourier transform infrared (FTIR) spectroscopy and Raman hyperspectral mapping (RHM) combined with advanced multivariate data analysis, were useful in studying the biochemical composition of PC tissue. Methods Here, we evaluated the potential of molecular imaging in differentiating three groups of PC tumors, which originate from different precursor lesions. Specifically, we comprehensively investigated adenocarcinomas (ACs): conventional ductal AC, intraductal papillary mucinous carcinoma, and ampulla of Vater AC. FTIR microspectroscopy and RHM maps of 24 PC tissue slides were obtained, and comprehensive advanced statistical analyses, such as hierarchical clustering and nonnegative matrix factorization, were performed on a total of 211,355 Raman spectra. Additionally, we employed deep learning technology for the same task of PC subtyping to enable automation. The so-called convolutional neural network (CNN) was trained to recognize spectra specific to each PC group and then employed to generate CNN-prediction-based tissue maps. To identify the DNA methylation spectral markers, we used differently methylated, isolated DNA and compared the observed spectral differences with the results obtained from cellular nuclei regions of PC tissues. Results The results showed significant differences among cancer tissues of the studied PC groups. The main findings are the varying content of β-sheet-rich proteins within the PC cells and alterations in the relative DNA methylation level. Our CNN model efficiently differentiated PC groups with 94% accuracy. The usage of CNN in the classification task did not require Raman spectral data preprocessing and eliminated the need for extensive knowledge of statistical methodologies. Conclusions Molecular spectroscopy combined with CNN technology is a powerful tool for PC detection and subtyping. The molecular fingerprint of DNA methylation and β-sheet cytoplasmic proteins established by our results is different for the main PC groups and allowed the subtyping of pancreatic tumors, which can improve patient management and increase their survival. Our observations are of key importance in understanding the variability of PC and allow translation of the methodology into clinical practice by utilizing liquid biopsy testing.

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Current Pathology Model of Pancreatic Cancer

Cited by 10 publications

References 255 publications

Vibrational spectroscopy – are we close to finding a solution for early pancreatic cancer diagnosis?

Vibrational spectroscopy – are we close to finding a solution for early pancreatic cancer diagnosis?

Combined analytical approach empowers precise spectroscopic interpretation of subcellular components of pancreatic cancer cells

Variabilities in global DNA methylation and β-sheet richness establish spectroscopic landscapes among subtypes of pancreatic cancer

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