Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer

Özkan, Çiğdem; Aktürk, Müjde; Altınova, Alev Eroğlu; Cerit, Ethem Turgay; Gülbahar, Özlem; Yalcin, Mehmet Muhittin; Çakır, Nuri; Törüner, Füsun Baloş

doi:10.1507/endocrj.ej15-0308

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…Our findings were in line with 2 other studies that showed significant increase in circulating PCSK9 levels in patients with short-term subclinical hypothyroidism, and overt hypothyroidism was significantly associated with elevations in total cholesterol, LDL-C and TSH and negatively correlated with FT4 in patients with subclinical hypothyroidism. 27,47 Other studies on euthyroid individuals also documented significant positive correlations between PCSK9 and TSH and lipids and negative correlations with FT3 and FT4. 48,49 In contrast, Gagnon et al did not find a significant relation between PCSK9 levels and TSH after acute administration of rhTSH in euthyroid subjects suggesting that chronic TSH stimulation is needed to affect hepatocyte PCSK9 secretion and elevation in human serum.…”

Section: Discussionmentioning

confidence: 93%

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

Sadik

Rashed

El-Sawy

2022

Clin Med Insights Endocrinol Diabetes

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Introduction: Overt and subclinical hypothyroidism are mostly associated with dyslipidemia, an essential cardiovascular risk factor. Recently, thyroid stimulating hormone (TSH) was identified to have a direct role on lipid metabolism via increased expression of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 plays a crucial role in lipid metabolism via regulating LDL-C levels. Thus, we aimed to evaluate circulating PCSK9 levels and to assess its relationship with serum TSH and lipids in newly diagnosed patients had overt and subclinical hypothyroidism. Methods: In our study, we enrolled 60 newly diagnosed untreated patients with overt and subclinical hypothyroidism and 30 euthyroid subjects served as the control group. Serum TSH, FT4, FT3, lipid profile and circulating PCSK9 levels using ELISA kits were measured in all subjects. Our data were summarized using mean ± SD or median and interquartile range. Correlations between PCSK9 expression levels and different variables were done using Spearman correlation coefficient. Results: Circulating PCSK9 median levels were significantly increased in patients had overt and subclinical hypothyroidism (12.45 ng/ml, 7.50 ng/ml respectively) compared to the control group (3.30 ng/ml) ( P < .001). Circulating PCSK9 levels significantly correlated positively with TSH, total cholesterol, triglycerides, and BMI, and negatively correlated with FT4 and FT3 among all studied subjects. Using multivariate regression analysis TSH was the only significant independent predictor of circulating PCSK9 ( P < .001). Conclusion: Our results supports the new implication of TSH in lipid metabolism via the significant association with PCSK9. Whether this relationship between TSH and PCSK9 is a cause or just an association needs further evaluation.

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Section: Discussionmentioning

confidence: 93%

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

Sadik

Rashed

El-Sawy

2022

Clin Med Insights Endocrinol Diabetes

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“…9 Altered PCSK9 expression has been reported in liver, gastric, and thyroid cancers. [10][11][12] On one hand, preclinical and clinical studies have confirmed that manipulating cholesterol metabolism can inhibit tumor growth, reshape the immune landscape, and enhance anti-tumor immunity 13 ; On the other, research data have demonstrated that PCSK9 participates in cell proliferation and apoptosis. 8 A nanoliposome anti-PCSK9 vaccine was reported to moderately reduce tumor growth and prolong the life span of mice with colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in Apc^Min/+ mice

Yang

Luo

et al. 2021

Int J Immunopathol Pharmacol

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Introduction Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipoprotein homeostasis in humans. Evolocumab is a selective PCSK9 inhibitor that can reduce low-density lipoprotein cholesterol (LDLC) level and decrease hypercholesterolemia. The current study aimed to explore whether PCSK9 increases the risk of colorectal cancer. Methods First, we utilized the classic intestinal tumor ApcMin/+ mouse model and PCSK9 knock-in (KI) mice to establish ApcMin/+PCSK9(KI) mice. Then, we investigated the effect of PCSK9 overexpression in ApcMin/+PCSK9(KI) mice and PCSK9 inhibition using evolocumab on the progression of intestinal tumors in vivo by hematoxylin and eosin (HE) staining, Western blot, and immunohistochemistry (IHC) assay. Results ApcMin/+PCSK9(KI) mice had higher numbers and larger sizes of adenomas, with 83.3% of these mice developing adenocarcinoma (vs. 16.7% of ApcMin/+ mice). However, treatment with evolocumab reduced the number and size of adenomas and prevented the development of adenocarcinomas in ApcMin/+ mice. PCSK9 overexpression reduced tumor cell apoptosis, the Bax/bcl-2 ratio, and the levels of cytokine signaling 3 protein (SOCS3) suppressors, but activated Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in intestinal tumors. In contrast, evolocumab treatment had the opposite effect on ApcMin/+mice. Conclusion PCSK9 might act as an oncogene or have an oncogenic role in the development and progression of colorectal cancer in vivo via activation of JAK2/STAT3/SOCS3 signaling.

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“…Moreover, many prior studies have already reported abnormal blood PCSK9 levels in patients with various types of cancer including liver, stomach, breast, and thyroid, indicating potential systemic changes in PCSK9 levels in those with cancer. [327][328][329][330][331][332][333] Additionally, several clinical studies have probed the connection between PCSK9 and the prognosis of cancer. [334][335][336][337][338] In this section, we meticulously evaluate the current body of research that highlights the potential of PCSK9 as a significant biomarker and promising therapeutic intervention for a variety of cancer types, including liver cancer, colorectal cancer (CRC), esophageal and gastric cancer (GC), as well as lung and breast cancer.…”

Section: Pcsk9 In Malignanciesmentioning

confidence: 99%

Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside

Bao,

Liang,

Chang

et al. 2024

Sig Transduct Target Ther

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases (CVD). This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9, extending beyond CVD to emphasize its significance in diverse physiological and pathological states, including liver diseases, infectious diseases, autoimmune disorders, and notably, cancer. Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors (LDLRs), elucidating its substantial impact on cholesterol homeostasis and cardiovascular health. It also details the evolution of PCSK9-targeted therapies, translating foundational bench discoveries into bedside applications for optimized patient care. The advent and clinical approval of innovative PCSK9 inhibitory therapies (PCSK9-iTs), including three monoclonal antibodies (Evolocumab, Alirocumab, and Tafolecimab) and one small interfering RNA (siRNA, Inclisiran), have marked a significant breakthrough in cardiovascular medicine. These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia, reducing cardiovascular risks, and have showcased profound value in clinical applications, offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders. Furthermore, emerging research, inclusive of our findings, unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment. This review also highlights PCSK9’s aberrant expression in various cancer forms, its association with cancer prognosis, and its crucial roles in carcinogenesis and cancer immunity. In conclusion, this synthesized review integrates existing knowledge and novel insights on PCSK9, providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders. It emphasizes the clinical value and effect of PCSK9-iT, underscoring its potential in advancing the landscape of biomedical research and its capabilities in heralding new eras in personalized medicine.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer

Cited by 9 publications

References 34 publications

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in Apc^Min/+ mice

Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside

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Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer

Cited by 9 publications

References 34 publications

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

The Relationship of Circulating Proprotein Convertase Subtilisin/Kexin Type 9 With TSH and Lipid Profile in Newly Diagnosed Patients With Subclinical and Overt Hypothyroidism

Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in ApcMin/+ mice

Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside

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Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in Apc^Min/+ mice