Platelet-Expressed Synaptophysin (pSyn) as Novel Biomarker in Neuroendocrine Malignancies

Hinterleitner, Martina; Sipos, Bence; Wagner, Verena; Grottenthaler, Julia M; Lauer, Ulrich M.; Zender, Lars

doi:10.3390/cancers13102286

Cited by 6 publications

(4 citation statements)

References 46 publications

(57 reference statements)

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“…With an analysis in only 6 out of 113 patients (5%), the determination of the 24 h urine level of 5-hydroxyindoleacetic acid has underrepresented diagnostic potential in this cohort. Besides distinct endocrine diagnostic tests for functionally active NENs, further biomarkers with higher expected specificity, like pro-gastrin-releasing peptide, pancreastatin or neurokinin A or platelet-expressed synaptophysin, are currently under preclinical investigation [69][70][71][72][73][74]. Based on this perspective, the investigation of circulating tumor cells and gene transcripts may further amplify the diagnostic repertoire, also in the context of NEN [75,76].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

Schmidt,

Hinterleitner,

Singer

et al. 2023

Cancers

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Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least “formally” limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

Schmidt,

Hinterleitner,

Singer

et al. 2023

Cancers

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“…In a recent report, Hinterleitner et al described elevated levels of platelet-expressed synaptophysin (pSyn) in NEN compared to healthy donors. A high expression of pSyn was shown to correlate with a shorter PFS, higher tumor stages, the presence of metastases and a higher tumor proliferation rate [ 148 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Neuroendocrine Tumor Biomarkers: Past, Present and Future

Komarnicki

Musiałkiewicz

Stańska

et al. 2022

JCM

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Neuroendocrine tumors are a heterogeneous group of neoplasms originating from the diffuse endocrine system. Depending on primary location and hormonal status, they range in terms of clinical presentation, prognosis and treatment. Functional tumors often develop symptoms indicating an excess of hormones produced by the neoplasm (exempli gratia insulinoma, glucagonoma and VIPoma) and can be diagnosed using monoanalytes. For non-functional tumors (inactive or producing insignificant amounts of hormones), universal biomarkers have not been established. The matter remains an important unmet need in the field of neuroendocrine tumors. Substances researched over the years, such as chromogranin A and neuron-specific enolase, lack the desired sensitivity and specificity. In recent years, the potential use of Circulating Tumor Cells or multianalytes such as a circulating microRNA and NETest have been widely discussed. They offer superior diagnostic parameters in comparison to traditional biomarkers and depict disease status in a more comprehensive way. Despite a lot of promise, no international standards have yet been developed regarding their routine use and clinical application. In this literature review, we describe the analytes used over the years and cover novel biomarkers that could find a use in the future. We discuss their pros and cons while showcasing recent advances in the field of neuroendocrine tumor biomarkers.

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“…Although pADAM17 levels appear to be enhanced in lung carcinoma [ 16 ], no significant difference was obtained between healthy donors and breast cancer patients. A high inter-donor variability was observed, particularly in tumor patients, which might reflect certain “malignant platelet phenotypes” associated with distinct disease characteristics [ 26 , 27 ]. As expression and activity of various proteins on the platelet surface reportedly are influenced by platelet activation [ 28 , 29 , 30 , 31 , 32 ], we explored whether pADAM17 is also regulated by this process.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?

Zhou¹,

Kropp

Hinterleitner³

et al. 2021

Diagnostics

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Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. Here, we report that platelet-derived ADAM17 (pADAM17) is regulated upon platelet activation of breast cancer patients, but not of healthy individuals. The observed downregulation of pADAM17 on platelets of cancer patients correlated with clinical parameters related to tumor progression including tumor stage and the occurrence of metastasis. Our data identify an association between platelet activation, modulation of platelet-derived ADAM17, and metastasis. In conclusion, we demonstrate that further development of pADAM17 as a liquid biomarker is warranted for monitoring disease progression in breast cancer.

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Platelet-Expressed Synaptophysin (pSyn) as Novel Biomarker in Neuroendocrine Malignancies

Cited by 6 publications

References 46 publications

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

Circulating Neuroendocrine Tumor Biomarkers: Past, Present and Future

Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?

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