Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer

Yusuke Nagasaki; Tetsuro Taki; Kotaro Nomura; Kenta Tane; Tomohiro Miyoshi; Joji Samejima; Keiju Aokage; Seiyu Jeong-Yoo Ohtani-Kim; Motohiro Kojima; Shingo Sakashita; Naoya Sakamoto; Shumpei Ishikawa; Kenji Suzuki; Masahiro Tsuboi; Genichiro Ishii

doi:10.1093/jnci/djae053

Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer

J Natl Cancer Inst. 2024 Mar 8:djae053. doi: 10.1093/jnci/djae053. Online ahead of print.

Authors

Yusuke Nagasaki^{1

2

3}, Tetsuro Taki¹, Kotaro Nomura², Kenta Tane², Tomohiro Miyoshi², Joji Samejima², Keiju Aokage², Seiyu Jeong-Yoo Ohtani-Kim^{1

2}, Motohiro Kojima^{1

4}, Shingo Sakashita^{1

4}, Naoya Sakamoto^{1

4}, Shumpei Ishikawa^{4

5}, Kenji Suzuki³, Masahiro Tsuboi², Genichiro Ishii^{1

6}

Affiliations

¹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
² Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
³ Department of General Thoracic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁴ Division of Pathology, National Cancer Center, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
⁵ Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁶ Division of Innovative Pathology and Laboratory Medicine, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

PMID: 38459590
DOI: 10.1093/jnci/djae053

Abstract

Objective: We quantified the pathological spatial intratumor heterogeneity (ITH) of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC).

Materials and methods: This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial ITH of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 (SHIP) for each tumor. The correlation between the SHIP values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation.

Results: Clinicopathological analysis showed correlations between high SHIP values and histological subtype (squamous cell carcinoma, p < .001) and vascular invasion (p = .004). Survival analysis revealed that patients with high SHIP values presented a significantly worse recurrence-free rate than those with low SHIP values (5-year RFS 26.3% vs 47.1%, p < .005). The impact of SHIP on cancer survival rates was verified through validation in an independent cohort. Moreover, high SHIP values were significantly associated with tumor recurrence in squamous cell carcinoma (5-year RFS 29.2% vs 52.8%, p < .05) and adenocarcinoma (5-year RFS 19.6% vs 43.0%, p < .01). Moreover, we demonstrated that a high SHIP value was an independent risk factor for tumor recurrence.

Conclusions: We presented an image analysis model to quantify the spatial ITH of protein expression in tumor tissues. This model demonstrated that the spatial ITH of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.