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      Expression of Tspan8 in Patients with Intrahepatic Cholangiocarcinoma and Its Relationship with Clinicopathological Features and Prognosis

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          Abstract

          The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan–Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.

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          Most cited references27

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          Systemic therapies for intrahepatic cholangiocarcinoma

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            Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates

            Intrahepatic cholangiocarcinoma accounts for 5% to 30% of all primary liver cancers, and its incidence has increased in the last 3 decades. Surgical resection remains the only potentially curative treatment but is associated with high tumor recurrence rates. The 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduced a new staging system for intrahepatic cholangiocarcinoma, which was previously staged the same as hepatocellular carcinoma. The recently published 8th edition has subdivided the T1 category to T1a and T1b based on a size cutoff of 5 cm, removed periductal invasion from the T4 category, and downstaged T4 tumors and regional lymph node metastasis from stage IV to IIIB. Continued international efforts to accurately stratify prognosis are important to counsel patients and guide treatment decisions.
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              TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling

              Cancer stem cells (CSCs) represent a major source of treatment resistance and tumor progression. However, regulation of CSCs stemness is not entirely understood. Here, we report that TSPAN8 expression is upregulated in breast CSCs, promotes the expression of the stemness gene NANOG, OCT4, and ALDHA1, and correlates with therapeutic resistance. Mechanistically, TSPAN8 interacts with PTCH1 and inhibits the degradation of the SHH/PTCH1 complex through recruitment of deubiquitinating enzyme ATXN3. This results in the translocation of SMO to cilia, downstream gene expression, resistance of CSCs to chemotherapeutic agents, and enhances tumor formation in mice. Accordingly, expression levels of TSPAN8, PTCH1, SHH, and ATXN3 are positively correlated in human breast cancer specimens, and high TSPAN8 and ATXN3 expression levels correlate with poor prognosis. These findings reveal a molecular basis of TSPAN8-enhanced Sonic Hedgehog signaling and highlight a role for TSPAN8 in promoting cancer stemness.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2021
                21 October 2021
                21 October 2021
                : 2021
                : 7475938
                Affiliations
                1Department of Hepatopancreatobiliary Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang 313000, China
                2Graduate School of Zhejiang University, Hangzhou, Zhejiang 310000, China
                3Department of Operating Room, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang 313000, China
                4Department of General Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang 313000, China
                Author notes

                Academic Editor: Songwen Tan

                Author information
                https://orcid.org/0000-0002-5956-333X
                Article
                10.1155/2021/7475938
                8553440
                110f641b-413f-4837-b5b0-1b05ab1e48cd
                Copyright © 2021 Zhenhua Tan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 September 2021
                : 20 September 2021
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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