Prognostic biomarkers in pancreatic ductal adenocarcinoma

Forskningsoutput: AvhandlingDoktorsavhandlingSamling av artiklar

Sammanfattning

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical surgical resection combined with chemotherapy, the only potentially curative treatment, is possible in only a small proportion of patients. Although overall survival is poor, marked variation exists between patients of the same tumor stage. New biomarkers could be helpful in predicting prognosis. Despite considerable research on potential biomarkers, since the discovery of CA19-9, none has gained a role in clinical practice. Identification of new biomarkers to predict PDAC patient outcome more accurately and to enhance our knowledge of the molecular mechanisms behind the disease is crucial. Differential diagnosis between PDAC and chronic pancreatitis (CP) can be challenging. A pancreatic mass can prove to be benign or malignant. A clear preoperative diagnosis would be valuable for patients to avoid unnecessary and extensive surgery. The standard serum- based marker for diagnosis of PDAC, CA19-9, has diagnostic limitations because it can be normal in patients with localized disease or high in patients with benign pancreatic disease, including CP. The aim of this thesis was to explore, tissue expression of tumor biomarkers in PDAC. The prognostic significance of these biomarkers in patient survival was evaluated. In each study, we used different biomarkers: podocalyxin (PODXL), PROX1, β-catenin, UCHL5, and REG4. In the last study, we also evaluated the diagnostic significance of serum REG4 levels in patients with PDAC and in those with CP. Immunohistochemical expression of tumor markers was evaluated in 154 surgical specimens and serum REG4 level in 130 samples from PDAC patients treated between 2000 and 2011. The CP control group comprised 34 patients who underwent resection because of suspicion of malignancy. PODXL, PROX1, β-catenin, and UCHL5 were independent prognostic markers. High tissue expression of PODXL prognosticated poor survival among PDAC patients compared with low tissue expression, whereas high tissue expression of both PROX1 and β-catenin was associated with increased survival. Positive nuclear UCHL5 expression was an independent factor for favorable prognosis. REG4 failed to be an independent marker of prognosis in PDAC, but serum REG4 levels were higher in PDAC than in CP suggesting its utility in differential diagnosis. These studies provide novel knowledge of potential prognostic tumor markers in PDAC. Moreover, we identified a serum biomarker, REG4, that may be useful in differential diagnosis between PDAC and CP.
Originalspråkengelska
Handledare
  • Haglund, Caj, Handledare
  • Seppänen, Hanna, Handledare
Tilldelningsdatum8 jun 2018
UtgivningsortHelsinki
Förlag
Tryckta ISBN978-951-51-4185-9
Elektroniska ISBN978-951-51-4186-6
StatusPublicerad - 2018
MoE-publikationstypG5 Doktorsavhandling (artikel)

Vetenskapsgrenar

  • 3111 Biomedicinska vetenskaper
  • 3122 Cancersjukdomar

Citera det här

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title = "Prognostic biomarkers in pancreatic ductal adenocarcinoma",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical surgical resection combined with chemotherapy, the only potentially curative treatment, is possible in only a small proportion of patients. Although overall survival is poor, marked variation exists between patients of the same tumor stage. New biomarkers could be helpful in predicting prognosis. Despite considerable research on potential biomarkers, since the discovery of CA19-9, none has gained a role in clinical practice. Identification of new biomarkers to predict PDAC patient outcome more accurately and to enhance our knowledge of the molecular mechanisms behind the disease is crucial. Differential diagnosis between PDAC and chronic pancreatitis (CP) can be challenging. A pancreatic mass can prove to be benign or malignant. A clear preoperative diagnosis would be valuable for patients to avoid unnecessary and extensive surgery. The standard serum- based marker for diagnosis of PDAC, CA19-9, has diagnostic limitations because it can be normal in patients with localized disease or high in patients with benign pancreatic disease, including CP. The aim of this thesis was to explore, tissue expression of tumor biomarkers in PDAC. The prognostic significance of these biomarkers in patient survival was evaluated. In each study, we used different biomarkers: podocalyxin (PODXL), PROX1, β-catenin, UCHL5, and REG4. In the last study, we also evaluated the diagnostic significance of serum REG4 levels in patients with PDAC and in those with CP. Immunohistochemical expression of tumor markers was evaluated in 154 surgical specimens and serum REG4 level in 130 samples from PDAC patients treated between 2000 and 2011. The CP control group comprised 34 patients who underwent resection because of suspicion of malignancy. PODXL, PROX1, β-catenin, and UCHL5 were independent prognostic markers. High tissue expression of PODXL prognosticated poor survival among PDAC patients compared with low tissue expression, whereas high tissue expression of both PROX1 and β-catenin was associated with increased survival. Positive nuclear UCHL5 expression was an independent factor for favorable prognosis. REG4 failed to be an independent marker of prognosis in PDAC, but serum REG4 levels were higher in PDAC than in CP suggesting its utility in differential diagnosis. These studies provide novel knowledge of potential prognostic tumor markers in PDAC. Moreover, we identified a serum biomarker, REG4, that may be useful in differential diagnosis between PDAC and CP.",
keywords = "Biomarkers, Tumor, Carcinoma, Pancreatic Ductal, +diagnosis, Catenins, Fluorouracil, Gastrointestinal Neoplasms, Guanidines, Homeodomain Proteins, Pancreatic Carcinoma, Pancreatitis, Chronic, Pancreatitis-Associated Proteins, Prognosis, Proteasome Endopeptidase Complex, Sialoglycoproteins, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, 3111 Biomedicine, 3122 Cancers",
author = "Kapo Saukkonen",
note = "M1 - 107 s. + liitteet",
year = "2018",
language = "English",
isbn = "978-951-51-4185-9",
publisher = "[K. Saukkonen]",
address = "Finland",

}

Prognostic biomarkers in pancreatic ductal adenocarcinoma. / Saukkonen, Kapo.

Helsinki : [K. Saukkonen], 2018. 107 s.

Forskningsoutput: AvhandlingDoktorsavhandlingSamling av artiklar

TY - THES

T1 - Prognostic biomarkers in pancreatic ductal adenocarcinoma

AU - Saukkonen, Kapo

N1 - M1 - 107 s. + liitteet

PY - 2018

Y1 - 2018

N2 - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical surgical resection combined with chemotherapy, the only potentially curative treatment, is possible in only a small proportion of patients. Although overall survival is poor, marked variation exists between patients of the same tumor stage. New biomarkers could be helpful in predicting prognosis. Despite considerable research on potential biomarkers, since the discovery of CA19-9, none has gained a role in clinical practice. Identification of new biomarkers to predict PDAC patient outcome more accurately and to enhance our knowledge of the molecular mechanisms behind the disease is crucial. Differential diagnosis between PDAC and chronic pancreatitis (CP) can be challenging. A pancreatic mass can prove to be benign or malignant. A clear preoperative diagnosis would be valuable for patients to avoid unnecessary and extensive surgery. The standard serum- based marker for diagnosis of PDAC, CA19-9, has diagnostic limitations because it can be normal in patients with localized disease or high in patients with benign pancreatic disease, including CP. The aim of this thesis was to explore, tissue expression of tumor biomarkers in PDAC. The prognostic significance of these biomarkers in patient survival was evaluated. In each study, we used different biomarkers: podocalyxin (PODXL), PROX1, β-catenin, UCHL5, and REG4. In the last study, we also evaluated the diagnostic significance of serum REG4 levels in patients with PDAC and in those with CP. Immunohistochemical expression of tumor markers was evaluated in 154 surgical specimens and serum REG4 level in 130 samples from PDAC patients treated between 2000 and 2011. The CP control group comprised 34 patients who underwent resection because of suspicion of malignancy. PODXL, PROX1, β-catenin, and UCHL5 were independent prognostic markers. High tissue expression of PODXL prognosticated poor survival among PDAC patients compared with low tissue expression, whereas high tissue expression of both PROX1 and β-catenin was associated with increased survival. Positive nuclear UCHL5 expression was an independent factor for favorable prognosis. REG4 failed to be an independent marker of prognosis in PDAC, but serum REG4 levels were higher in PDAC than in CP suggesting its utility in differential diagnosis. These studies provide novel knowledge of potential prognostic tumor markers in PDAC. Moreover, we identified a serum biomarker, REG4, that may be useful in differential diagnosis between PDAC and CP.

AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Radical surgical resection combined with chemotherapy, the only potentially curative treatment, is possible in only a small proportion of patients. Although overall survival is poor, marked variation exists between patients of the same tumor stage. New biomarkers could be helpful in predicting prognosis. Despite considerable research on potential biomarkers, since the discovery of CA19-9, none has gained a role in clinical practice. Identification of new biomarkers to predict PDAC patient outcome more accurately and to enhance our knowledge of the molecular mechanisms behind the disease is crucial. Differential diagnosis between PDAC and chronic pancreatitis (CP) can be challenging. A pancreatic mass can prove to be benign or malignant. A clear preoperative diagnosis would be valuable for patients to avoid unnecessary and extensive surgery. The standard serum- based marker for diagnosis of PDAC, CA19-9, has diagnostic limitations because it can be normal in patients with localized disease or high in patients with benign pancreatic disease, including CP. The aim of this thesis was to explore, tissue expression of tumor biomarkers in PDAC. The prognostic significance of these biomarkers in patient survival was evaluated. In each study, we used different biomarkers: podocalyxin (PODXL), PROX1, β-catenin, UCHL5, and REG4. In the last study, we also evaluated the diagnostic significance of serum REG4 levels in patients with PDAC and in those with CP. Immunohistochemical expression of tumor markers was evaluated in 154 surgical specimens and serum REG4 level in 130 samples from PDAC patients treated between 2000 and 2011. The CP control group comprised 34 patients who underwent resection because of suspicion of malignancy. PODXL, PROX1, β-catenin, and UCHL5 were independent prognostic markers. High tissue expression of PODXL prognosticated poor survival among PDAC patients compared with low tissue expression, whereas high tissue expression of both PROX1 and β-catenin was associated with increased survival. Positive nuclear UCHL5 expression was an independent factor for favorable prognosis. REG4 failed to be an independent marker of prognosis in PDAC, but serum REG4 levels were higher in PDAC than in CP suggesting its utility in differential diagnosis. These studies provide novel knowledge of potential prognostic tumor markers in PDAC. Moreover, we identified a serum biomarker, REG4, that may be useful in differential diagnosis between PDAC and CP.

KW - Biomarkers, Tumor

KW - Carcinoma, Pancreatic Ductal

KW - +diagnosis

KW - Catenins

KW - Fluorouracil

KW - Gastrointestinal Neoplasms

KW - Guanidines

KW - Homeodomain Proteins

KW - Pancreatic Carcinoma

KW - Pancreatitis, Chronic

KW - Pancreatitis-Associated Proteins

KW - Prognosis

KW - Proteasome Endopeptidase Complex

KW - Sialoglycoproteins

KW - Tumor Suppressor Proteins

KW - Ubiquitin Thiolesterase

KW - 3111 Biomedicine

KW - 3122 Cancers

M3 - Doctoral Thesis

SN - 978-951-51-4185-9

PB - [K. Saukkonen]

CY - Helsinki

ER -