Computerized tertiary lymphoid structures density on H&E-images is a prognostic biomarker in resectable lung adenocarcinoma

Yumeng Wang; Huan Lin; Ningning Yao; Xiaobo Chen; Bingjiang Qiu; Yanfen Cui; Yu Liu; Bingbing Li; Chu Han; Zhenhui Li; Wei Zhao; Zimin Wang; Xipeng Pan; Cheng Lu; Jun Liu; Zhenbing Liu; Zaiyi Liu

doi:10.1016/j.isci.2023.107635

Computerized tertiary lymphoid structures density on H&E-images is a prognostic biomarker in resectable lung adenocarcinoma

iScience. 2023 Aug 16;26(9):107635. doi: 10.1016/j.isci.2023.107635. eCollection 2023 Sep 15.

Authors

Yumeng Wang^{1

2}, Huan Lin^{3

2

4}, Ningning Yao⁵, Xiaobo Chen⁶, Bingjiang Qiu^{3

2

7}, Yanfen Cui^{3

2

5

7}, Yu Liu², Bingbing Li⁸, Chu Han^{3

2

9}, Zhenhui Li¹⁰, Wei Zhao¹¹, Zimin Wang¹, Xipeng Pan¹, Cheng Lu^{1

3

2

9}, Jun Liu¹¹, Zhenbing Liu¹, Zaiyi Liu^{1

3

2}

Affiliations

¹ School of Computer Science and Information Security, Guilin University of Electronic Technology, Guilin 541004, China.
² Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou 510080, China.
³ Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
⁴ School of Medicine, South China University of Technology, Guangzhou 510006, China.
⁵ Department of Radiobiology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University; Taiyuan 030013, China.
⁶ First Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.
⁷ Guangdong Cardiovascular Institute, Guangzhou 510080, China.
⁸ Department of Pathology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, 49 Dagong Road, Ganzhou 341000, China.
⁹ Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
¹⁰ Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.
¹¹ Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.

Abstract

The increased amount of tertiary lymphoid structures (TLSs) is associated with a favorable prognosis in patients with lung adenocarcinoma (LUAD). However, evaluating TLSs manually is an experience-dependent and time-consuming process, which limits its clinical application. In this multi-center study, we developed an automated computational workflow for quantifying the TLS density in the tumor region of routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The association between the computerized TLS density and disease-free survival (DFS) was further explored in 802 patients with resectable LUAD of three cohorts. Additionally, a Cox proportional hazard regression model, incorporating clinicopathological variables and the TLS density, was established to assess its prognostic ability. The computerized TLS density was an independent prognostic biomarker in patients with resectable LUAD. The integration of the TLS density with clinicopathological variables could support individualized clinical decision-making by improving prognostic stratification.

Keywords: Health informatics; cancer; computational bioinformatics.