Usefulness of Human Telomerase Reverse Transcriptase in Pancreatic Juice as a Biomarker of Pancreatic Malignancy

Nakashima, Akira; Murakami, Yoshiaki; Uemura, Kenichiro; Hayashidani, Yasuo; Sudo, Takeshi; Hashimoto, Yasushi; Ohge, Hiroki; Oda, Miyo; Sueda, Taijiro; Hiyama, Eiso

doi:10.1097/mpa.0b013e3181a16d28

Cited by 29 publications

(21 citation statements)

References 29 publications

(23 reference statements)

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“…An examination of hTERT expression in pancreatic juice samples (obtained after secretin stimulation)from patients with PC and IPMN revealed that while cytology was 47% sensitive and 57% accurate in distinguishing malignant cells from benign cells, a positive staining for hTERT was nearly 85% sensitive and over 80% accurate in achieving this distinction [142]. Significantly, among the PC cases, hTERT staining correctly identified 17 out of 21 cases that were negative for malignant cells by cytology.…”

Section: Biomarkers In Body Fluidsmentioning

confidence: 99%

Current status of molecular markers for early detection of sporadic pancreatic cancer

Chakraborty

Baine

Sasson

et al. 2011

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Pancreatic cancer (PC) is a highly lethal malignancy with near 100% mortality. This is in part due to the fact that most patients present with metastatic or locally advanced disease at the time of diagnosis. Significantly, in nearly 95% of PC patients there is neither an associated family history of PC nor of diseases known to be associated with an increased risk of PC. These groups of patients who comprise the bulk of PC cases are termed as "sporadic PC" in contrast to the familial PC cases that comprise only about 5% of all PCs. Given the insidious onset of the malignancy and its extreme resistance to chemo and radiotherapy, an abundance of research in recent years has focused on identifying biomarkers for the early detection of PC, specifically aiming at the sporadic PC cohort. However, while several studies have established that asymptomatic individuals with a positive family history of PC and those with certain heritable syndromes are candidates for PC screening, the role of screening in identifying sporadic PC is still an unsettled question. The present review attempts to assess this critical question by investigating the recent advances made in molecular markers with potential use in the early diagnosis of sporadic PC-the largest cohort of PC cases worldwide. It also outlines a novel yet simple risk-factor based stratification system that could be potentially employed by clinicians to identify those individuals who at an elevated-risk for the development of sporadic PC and therefore candidates for screening. Keywords diagnosis; PanIN; biomarkers PrologueIt seems that pancreatic cancer (PC) has recently crept further and further into the consciousness of the general public. The news that Luciano Pavarotti, the renowned opera Address for Correspondence: Surinder K. Batra, Ph.D., Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, U.S.A., Phone: 402-559-5455; Fax: 402-559-6650. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptBiochim Biophys Acta. Author manuscript; available in PMC 2012 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript singer and one of the legendary "three tenors" had been diagnosed with PC came as a shock to millions of his followers the world over. A year-and-a-half later, the famous actor and heartthrob, Patrick Swayze, also received the diagnosis of PC and succumbed to his disease in just 19 months. Former United States...

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Section: Biomarkers In Body Fluidsmentioning

confidence: 99%

Current status of molecular markers for early detection of sporadic pancreatic cancer

Chakraborty

Baine

Sasson

et al. 2011

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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“…An alternative to measuring telomerase activity is to measure the expression of one of its RNA components, TERT, whose expression closely correlates with telomerase activity and can be more readily assayed in clinical samples (30). TERT RNA levels in pancreatic juice samples collected from the pancreatic duct can accurately differentiate benign from malignant pancreatic lesions (31–33). Studies have also measured TERT RNA in resected pancreatic cystic neoplasm specimens as a marker of telomerase activity (34).…”

Section: Introductionmentioning

confidence: 99%

Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas

Hata

Molin

Suenaga

et al. 2016

Clinical Cancer Research

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Purpose Pancreatic cysts frequently pose clinical dilemmas. On one hand, cysts with high-grade dysplasia offer opportunities for cure, on the other hand, those with low-grade dysplasia are easily over treated. Cyst fluid markers have the potential to improve the evaluation of these cysts. Since telomerase activity is commonly activated in malignant cells, we evaluated the diagnostic performance of cyst fluid telomerase activity measurements for predicting histologic grade. Experimental design Telomerase activity was measured using telomerase repeat amplification with digital-droplet PCR in surgically-aspirated cyst fluid samples from 219 patients who underwent pancreatic resection for a cystic lesion (184, discovery, 35 validation) and 36 patients who underwent endoscopic ultrasound fine needle aspiration. Methodological and clinical factors associated with telomerase activity were examined. Results Telomerase activity was reduced in samples that had undergone prior thawing. Among 119 samples not previously thawed, surgical cyst fluids from cystic neoplasms with high-grade dysplasia +/− associated invasive cancer had higher telomerase activity (median [interquartile range], 1158 [295.9–13033] copies/μL of cyst fluid than those without (19.74 [2.58–233.6] copies/μL) (P < 0.001). Elevated cyst fluid telomerase activity had a diagnostic accuracy for invasive cancer/high-grade dysplasia of 88.1% (discovery), 88.6% (validation), and 88.2% (merged). Among cysts classified preoperatively as having “worrisome features”, cyst fluid telomerase activity had high diagnostic performance (sensitivity 73.7%, specificity 90.6%, accuracy, 86.1%). In multivariate analysis, telomerase activity independently predicted the presence of invasive cancer/high-grade dysplasia. Conclusion Cyst fluid telomerase activity can be a useful predictor of the neoplastic grade of pancreatic cysts.

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“…Exocrine pancreatic secretions, or pancreatic juice, collected from the second part of the duodenum after stimulation with intravenous synthetic human secretin using an upper endoscope 3-5 have been analyzed for molecular markers associated with pancreatic ductal adenocarcinoma (PDAC) 6, 7. Protein and gene expression profiles in the pancreatic juice of patients with PDAC have revealed novel protein markers and indicator genes that might be useful for PDAC diagnosis 8, 9.…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer

Wang¹,

Raimondo²,

Guha³

et al. 2014

J. Cancer

101

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Development of sensitive and specific biomarkers, preferably those circulating in body fluids is critical for early diagnosis of cancer. This study performed profiling of microRNAs (miRNAs) in exocrine pancreatic secretions (pancreatic juice) by microarray analysis utilizing pancreatic juice from 6 pancreatic ductal adenocarcinoma (PDAC) patients and two pooled samples from 6 non-pancreatic, non-healthy (NPNH) as controls. Differentially circulating miRNAs were subsequently validated in 88 pancreatic juice samples from 50 PDAC, 19 chronic pancreatitis (CP) patients and 19 NPNH controls. A marked difference in the profiles of four circulating miRNAs (miR-205, miR-210, miR-492, and miR-1427) was observed in pancreatic juice collected from patients with PDAC and those without pancreatic disease. Elevated levels of the four miRNAs together predicted PDAC with a specificity of 88% and sensitivity of 87%. Inclusion of serum CA19-9 level increased the sensitivity to 91% and the specificity to 100%. Enrichment of the four miRNAs in pancreatic juice was associated with decreased OS, as was the combination of miR-205 and miR-210. Higher contents of miR-205 and miR-210 were also associated with lymph node metastasis. Elevated levels of circulating miR-205, miR-210, miR-492, and miR-1247 in pancreatic juice are, therefore, promising candidate biomarkers of disease and poor prognosis in patients with PDAC.

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Usefulness of Human Telomerase Reverse Transcriptase in Pancreatic Juice as a Biomarker of Pancreatic Malignancy

Abstract: Our results suggested that the assessment of hTERT expression in preoperative pancreatic juice increased the sensitivity and accuracy of diagnosis of PDACs and malignant IPMNs without using special techniques.

Cited by 29 publications

References 29 publications

Current status of molecular markers for early detection of sporadic pancreatic cancer

Current status of molecular markers for early detection of sporadic pancreatic cancer

Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas

Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer

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