Identification of cold tumor induction-related markers in pancreatic cancer and the clinical implication of PCDH7.

IF 2.7 3区医学 Q3 ONCOLOGY

Journal of Cancer Research and Clinical Oncology Pub Date : 2025-01-24 DOI:10.1007/s00432-025-06095-z

Yuki Mochida, Kenoki Ohuchida, Bo Zhang, Yutaka Yamada, Chikanori Tsutsumi, Akihiro Kubo, Koki Oyama, Tomohiko Shinkawa, Chika Iwamoto, Nobuhiro Torata, Toshiya Abe, Noboru Ideno, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura

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引用次数: 0

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is considered a "cold" tumor because the tumor immune microenvironment (TIME) exhibits poor intratumoral T-cell infiltration. This study aimed to identify the marker genes associated with induction of cold TIME in PDAC cells.

Methods: We orthotopically transplanted 10 primary cultures of PDAC derived from KrasG12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) mice into immunocompetent mice and evaluated TIME by immunohistochemistry (IHC) staining of CD8. We divided primary cultures into two groups: cold TIME group with low CD8⁺ T-cell infiltration and a hot TIME group with high infiltration. RNA sequencing was performed to identify specific genes in the cold TIME group, and single-cell RNA sequencing (scRNA-seq) data was used for validation. IHC was performed to evaluate expressions in human PDAC samples.

Results: We identified six genes specific in PDAC cells to the cold TIME group by RNA sequencing; these were defined as "cold tumor induction-related genes". Human PDAC scRNA-seq data revealed that cold tumor induction-related genes were significantly and negatively correlated with the number of CD8⁺ T-cells (p = 0.0341). These genes included protocadherin 7 (PCDH7). High expression of PCDH7 significantly and negatively correlated with the number of CD8⁺ T-cells in scRNA-seq (p = 0.0474) and IHC (p = 0.0110) data using human PDAC samples. PCDH7 was an independent factor for poor prognosis in PDAC (overall survival: hazard ratio = 2.07, p = 0.0367).

Conclusion: PCDH7 is a prognostic marker associated with CD8⁺ T-cell infiltration for PDAC patients.

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来源期刊

Journal of Cancer Research and Clinical Oncology 医学-肿瘤学

CiteScore

4.00

自引率

2.80%

发文量

577

审稿时长

2 months

期刊介绍： The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.