PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer

Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Tetsushi Kubota, Katsuyuki Aoyama, Takehiro Tanaka, Satoru Kikuchi, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

Original languageEnglish
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Mar 15 2019

Fingerprint

Tumor-Infiltrating Lymphocytes
Microsatellite Instability
Stomach Neoplasms
Biomarkers
Ligands
Kaplan-Meier Estimate
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. / Morihiro, Toshiaki; Kuroda, Shinji; Kanaya, Nobuhiko; Kakiuchi, Yoshihiko; Kubota, Tetsushi; Aoyama, Katsuyuki; Tanaka, Takehiro; Kikuchi, Satoru; Nagasaka, Takeshi; Nishizaki, Masahiko; Kagawa, Shunsuke; Tazawa, Hiroshi; Fujiwara, Toshiyoshi.

In: Scientific reports, Vol. 9, No. 1, 15.03.2019.

Research output: Contribution to journalArticle

@article{1275fc6488d0497ba5627fd98a69a9ea,
title = "PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer",
abstract = "While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5{\%} tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5{\%} (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.",
author = "Toshiaki Morihiro and Shinji Kuroda and Nobuhiko Kanaya and Yoshihiko Kakiuchi and Tetsushi Kubota and Katsuyuki Aoyama and Takehiro Tanaka and Satoru Kikuchi and Takeshi Nagasaka and Masahiko Nishizaki and Shunsuke Kagawa and Hiroshi Tazawa and Toshiyoshi Fujiwara",
year = "2019",
month = "3",
day = "15",
doi = "10.1038/s41598-019-41177-2",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer

AU - Morihiro, Toshiaki

AU - Kuroda, Shinji

AU - Kanaya, Nobuhiko

AU - Kakiuchi, Yoshihiko

AU - Kubota, Tetsushi

AU - Aoyama, Katsuyuki

AU - Tanaka, Takehiro

AU - Kikuchi, Satoru

AU - Nagasaka, Takeshi

AU - Nishizaki, Masahiko

AU - Kagawa, Shunsuke

AU - Tazawa, Hiroshi

AU - Fujiwara, Toshiyoshi

PY - 2019/3/15

Y1 - 2019/3/15

N2 - While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

AB - While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

UR - http://www.scopus.com/inward/record.url?scp=85062998026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062998026&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-41177-2

DO - 10.1038/s41598-019-41177-2

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -