The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions

Holah, Nanis Shawky; El-Azab, Dina S; Aiad, Hayam A; Sweed, Dina

doi:10.1097/pai.0000000000000363

Cited by 9 publications

(14 citation statements)

References 30 publications

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“…In particular, the genes coding for the SPINK1 and GPC3 were recently reported to be (25)(26)(27). As described earlier by our group (28) SPINK1, also known as tumor-associated trypsin inhibitor, was typically overexpressed in HCV-positive HCCs, underlining the theory that SPINK1 may be able to interrupt apoptosis of viralinfected hepatocytes by cellular host defense (29) as one of the postulated mechanisms of this gene in hepatocarcinogegesis.…”

Section: Discussionmentioning

confidence: 66%

Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma

Hass

Vogel

Scheurlen

et al. 2016

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Section: Discussionmentioning

confidence: 66%

Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma

Hass

Vogel

Scheurlen

et al. 2016

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“…Studies indicate that SPINK1 regulates HCC progression. For instance, SPINK1 differentiates a well-differentiated HCC from a high-grade dysplastic nodule ( 12 ). Moreover, SPINK1 is significantly upregulated in HCC tissues compared with corresponding nonmalignant tissues ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies indicate that SPINK1 has been detected in multiple types of cancers including bladder, renal, colorectal, prostate, and liver cancers ( 8 , 11 ). For HCC, high SPINK1 expression acts as prognostic and diagnostic biomarkers that promote cell proliferation and metastasis ( 12 , 13 ). This denotes the important roles of SPINK1 in HCC progression.…”

Section: Introductionmentioning

confidence: 99%

circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1

Lin

et al. 2021

Front. Oncol.

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The roles of serine protease inhibitor Kazal type 1 (SPINK1) in multiple types of cancers have been significantly documented. However, its specific roles in hepatocellular carcinoma (HCC) remain to be investigated. This study found that SPINK1 is upregulated in HCC and its upregulation correlates with poor prognosis. Besides, functional assays revealed that SPINK1 promotes cell proliferation, cell cycle, and invasion in vitro. Through bioinformatics analysis, we speculate that circRPS16 regulates SPINK1 expression by sponging miR-876-5p. This was further verified by the dual-luciferase reporter and fluorescent in situ hybridization (FISH) assays. Subsequently, rescue assays verified that circRPS16 promotes cell proliferation, cell cycle, and invasion through miR-876-5p. Importantly, silencing circRPS16 inhibited tumor growth by downregulating SPINK1 expression in vivo. Collectively, our results confirm that SPINK1 is a downstream target of circRPS16. Besides, circRPS16 and SPINK1 are oncogenic factors in HCC progression; they provide novel diagnostic and therapeutic targets for HCC patients.

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“…In liver cancer, a low SPINK1 expression score was found in cirrhosis patients compared with that in well-differentiated hepatocellular carcinoma (WD-HCC) patients. In addition, a significant difference in SPINK1 expression between WD-HCC and high-grade dysplastic nodules (HGDNs) was observed, suggesting a diagnostic role for SPINK1 in hepatocellular carcinoma [41]. The SPINK1 expression level in another hepatocellular carcinoma cohort was investigated using a tissue assay of 273 paired tumor and paratumor tissues.…”

Section: Spink1 Expression In Cancersmentioning

confidence: 99%

Functional Roles of SPINK1 in Cancers

Lin

2021

IJMS

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Serine Peptidase Inhibitor Kazal Type 1 (SPINK1) is a secreted protein known as a protease inhibitor of trypsin in the pancreas. However, emerging evidence shows its function in promoting cancer progression in various types of cancer. SPINK1 modulated tumor malignancies and induced the activation of the downstream signaling of epidermal growth factor receptor (EGFR) in cancer cells, due to the structural similarity with epidermal growth factor (EGF). The discoverable SPINK1 somatic mutations, expressional signatures, and prognostic significances in various types of cancer have attracted attention as a cancer biomarker in clinical applications. Emerging findings further clarify the direct and indirect biological effects of SPINK1 in regulating cancer proliferation, metastasis, drug resistance, transdifferentiation, and cancer stemness, warranting the exploration of the SPINK1-mediated molecular mechanism to identify a therapeutic strategy. In this review article, we first integrate the transcriptomic data of different types of cancer with clinical information and recent findings of SPINK1-mediated malignant phenotypes. In addition, a comprehensive summary of SPINK1 expression in a pan-cancer panel and individual cell types of specific organs at the single-cell level is presented to indicate the potential sites of tumorigenesis, which has not yet been reported. This review aims to shed light on the roles of SPINK1 in cancer and provide guidance and potential directions for scientists in this field.

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The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions

Abstract: SPINK1 can be used to differentiate between a WD-HCC and a HGDN with high diagnostic validity.

Cited by 9 publications

References 30 publications

Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma

Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma

circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1

Functional Roles of SPINK1 in Cancers

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