| RRC ID |
65403
|
| 著者 |
Yugawa K, Itoh S, Yoshizumi T, Iseda N, Tomiyama T, Morinaga A, Toshima T, Harada N, Kohashi K, Oda Y, Mori M.
|
| タイトル |
CMTM6 Stabilizes PD-L1 Expression and Is a New Prognostic Impact Factor in Hepatocellular Carcinoma.
|
| ジャーナル |
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.
|
| 巻・号 |
5(2)
|
| ページ |
334-348
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7(RCB1366)
Hep G2(RCB1886) |
