Artificial intelligence-quantified tumour-lymphocyte spatial interaction predicts disease-free survival in resected lung adenocarcinoma: A graph-based, multicentre study

Comput Methods Programs Biomed. 2023 Aug:238:107617. doi: 10.1016/j.cmpb.2023.107617. Epub 2023 May 18.

Abstract

Background and objective: A high degree of lymphocyte infiltration is related to superior outcomes amongst patients with lung adenocarcinoma. Recent evidence indicates that the spatial interactions between tumours and lymphocytes also influence the anti-tumour immune responses, but the spatial analysis at the cellular level remains insufficient.

Methods: We proposed an artificial intelligence-quantified Tumour-Lymphocyte Spatial Interaction score (TLSI-score) by calculating the ratio between the number of spatial adjacent tumour-lymphocyte and the number of tumour cells based on topology cell graph constructed using H&E-stained whole-slide images. The association of TLSI-score with disease-free survival (DFS) was explored in 529 patients with lung adenocarcinoma across three independent cohorts (D1, 275; V1, 139; V2, 115).

Results: After adjusting for pTNM stage and other clinicopathologic risk factors, a higher TLSI-score was independently associated with longer DFS than a low TLSI-score in the three cohorts [D1, adjusted hazard ratio (HR), 0.674; 95% confidence interval (CI) 0.463-0.983; p = 0.040; V1, adjusted HR, 0.408; 95% CI 0.223-0.746; p = 0.004; V2, adjusted HR, 0.294; 95% CI 0.130-0.666; p = 0.003]. By integrating the TLSI-score with clinicopathologic risk factors, the integrated model (full model) improves the prediction of DFS in three independent cohorts (C-index, D1, 0.716 vs. 0.701; V1, 0.666 vs. 0.645; V2, 0.708 vs. 0.662) CONCLUSIONS: TLSI-score shows the second highest relative contribution to the prognostic prediction model, next to the pTNM stage. TLSI-score can assist in the characterising of tumour microenvironment and is expected to promote individualized treatment and follow-up decision-making in clinical practice.

Keywords: Artificial intelligence; Lung adenocarcinoma; Microenvironment; Spatial interaction; Tumour-infiltrating lymphocyte.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma of Lung* / surgery
  • Adenocarcinoma* / surgery
  • Artificial Intelligence
  • Disease-Free Survival
  • Humans
  • Lung Neoplasms* / surgery
  • Lymphocytes
  • Prognosis
  • Retrospective Studies
  • Tumor Microenvironment