RRC ID 65403
Author Yugawa K, Itoh S, Yoshizumi T, Iseda N, Tomiyama T, Morinaga A, Toshima T, Harada N, Kohashi K, Oda Y, Mori M.
Title CMTM6 Stabilizes PD-L1 Expression and Is a New Prognostic Impact Factor in Hepatocellular Carcinoma.
Journal Hepatol Commun
Abstract CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a regulator of programmed death ligand 1 (PD-L1), which induces antitumor immunity in several cancers. This study aimed to clarify the relationship between CMTM6 and PD-L1 expression and clinical outcomes in patients with hepatocellular carcinoma (HCC). In total, 259 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for CMTM6 and PD-L1 was performed. The relationships between CMTM6 expression and the clinicopathological characteristics and outcomes were analyzed. Additionally, the stabilization of PD-L1 expression and regulation of malignant activities by CMTM6 were examined in vitro. Our patients were divided into high (n = 65, 25.1%) and low (n = 194, 74.9%) CMTM6 expression groups. High CMTM6 expression was significantly associated with malignant aggregates, including poor differentiation (P < 0.0001), microscopic intrahepatic metastasis (P = 0.0369), and multiple intrahepatic recurrences (P = 0.0211). CMTM6 expression was significantly correlated with PD-L1 expression in HCC tissues (P < 0.0001). The patients were classified into three groups: high CMTM6/PD-L1 positive (n = 21), high CMTM6/ PD-L1 negative (n = 44), and low CMTM6 (n = 194) expression pattern groups. Overall survival was significantly different among the three groups (P < 0.0001). Additionally, immunohistochemical double staining revealed that CMTM6 and PD-L1 were co-expressed on HCC cells. In vitro, PD-L1 expression was enhanced at late time points in the presence of CMTM6 expression. CMTM6 also regulated epithelial-to-mesenchymal transition and stemness phenotypes in HCC cells. Conclusion: Our large cohort study found that CMTM6 co-expressed with PD-L1 was strongly associated with the clinical outcome in patients with HCC. The evaluation of CMTM6 combined with PD-L1 in HCC might be useful for patient selection in immune checkpoint therapy.
Volume 5(2)
Pages 334-348
Published 2021-2-1
DOI 10.1002/hep4.1643
PII HEP41643
PMID 33553979
PMC PMC7850307
MeSH Adult Aged Aged, 80 and over B7-H1 Antigen / biosynthesis* Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cohort Studies Epithelial-Mesenchymal Transition Female Humans Liver Neoplasms / metabolism* Liver Neoplasms / pathology MARVEL Domain-Containing Proteins / biosynthesis* Male Middle Aged Myelin Proteins / biosynthesis* Prognosis
Human and Animal Cells HuH-7(RCB1366) Hep G2(RCB1886)