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.


Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
04 2020
Historique:
received: 07 11 2019
accepted: 19 02 2020
revised: 15 02 2020
pubmed: 3 3 2020
medline: 24 11 2020
entrez: 3 3 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32115573
doi: 10.1038/s41388-020-1237-0
pii: 10.1038/s41388-020-1237-0
pmc: PMC7176584
doi:

Substances chimiques

B7-H1 Antigen 0
CD274 protein, human 0
Chemokines, C 0
Neoplasm Proteins 0
XCL1 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3541-3554

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Auteurs

Ryo Tamura (R)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Kosuke 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.

Hirofumi Nakaoka (H)

Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan.

Nozomi Yachida (N)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Manako Yamaguchi (M)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Kazuaki Suda (K)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Tatsuya Ishiguro (T)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Koji Nishino (K)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Hiroshi Ichikawa (H)

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Keiichi Homma (K)

Department of Pathology, Niigata Cancer Center Hospital, Niigata, 951-8133, Japan.

Akira Kikuchi (A)

Department of Gynecology, Niigata Cancer Center Hospital, Niigata, 951-8133, Japan.

Yutaka Ueda (Y)

Department of Obstetrics and Gynecology, Osaka University School of Medicine, Suita, 565-0871, Japan.

Yuji Takei (Y)

Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, 329-0498, Japan.

Hiroyuki Fujiwara (H)

Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, 329-0498, Japan.

Teiichi Motoyama (T)

Department of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Shujiro Okuda (S)

Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Toshifumi Wakai (T)

Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Ituro Inoue (I)

Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan.

Takayuki Enomoto (T)

Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

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