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XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary.
Tamura, Ryo; Yoshihara, Kosuke; Nakaoka, Hirofumi; Yachida, Nozomi; Yamaguchi, Manako; Suda, Kazuaki; Ishiguro, Tatsuya; Nishino, Koji; Ichikawa, Hiroshi; Homma, Keiichi; Kikuchi, Akira; Ueda, Yutaka; Takei, Yuji; Fujiwara, Hiroyuki; Motoyama, Teiichi; Okuda, Shujiro; Wakai, Toshifumi; Inoue, Ituro; Enomoto, Takayuki.
Afiliação
  • Tamura R; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Yoshihara K; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan. yoshikou@med.niigata-u.ac.jp.
  • Nakaoka H; Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan.
  • Yachida N; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Yamaguchi M; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Suda K; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Ishiguro T; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Nishino K; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Ichikawa H; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Homma K; Department of Pathology, Niigata Cancer Center Hospital, Niigata, 951-8133, Japan.
  • Kikuchi A; Department of Gynecology, Niigata Cancer Center Hospital, Niigata, 951-8133, Japan.
  • Ueda Y; Department of Obstetrics and Gynecology, Osaka University School of Medicine, Suita, 565-0871, Japan.
  • Takei Y; Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, 329-0498, Japan.
  • Fujiwara H; Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, 329-0498, Japan.
  • Motoyama T; Department of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Okuda S; Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Wakai T; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
  • Inoue I; Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan.
  • Enomoto T; Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Oncogene ; 39(17): 3541-3554, 2020 04.
Article em En | MEDLINE | ID: mdl-32115573
Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Teratoma / Carcinoma de Células Escamosas / Regulação Neoplásica da Expressão Gênica / Linfócitos do Interstício Tumoral / Linfócitos T CD8-Positivos / Quimiocinas C / Antígeno B7-H1 / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Teratoma / Carcinoma de Células Escamosas / Regulação Neoplásica da Expressão Gênica / Linfócitos do Interstício Tumoral / Linfócitos T CD8-Positivos / Quimiocinas C / Antígeno B7-H1 / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article