Cross-platform transportability of ligand–receptor communication scores for prognosis in lung adenocarcinoma: a systematic benchmark of three scoring constructs across four cohorts
Year: 2026
Type: preprint
Abstract: Ligand–receptor communication scores derived from bulk tumour transcriptomes have been proposed as prognostic markers in lung adenocarcinoma, but whether they survive a platform change has never been benchmarked head-to-head. We quantified communication competence for 2,459 measurable CellChatDB v2 pairs in four cohorts (1,355 tumours, 529 deaths) using three scoring constructs — a z-based construct (Z-CP), a rank co-elevation construct invariant to monotone transformations (RCE) and a cell-type-resolved construct built on marker-anchored deconvolution (CTRC) — with nested cross-validation, formal equivalence testing (two one-sided tests, margin ΔC = 0.05) and a graded platform-shift simulation. In the discovery cohort the constructs performed comparably (cross-validated C-index 0.543–0.585); in the three external cohorts every construct landed in the same modest band (C-index 0.46–0.56). RCE was statistically equivalent to Z-CP in both adequately powered cohorts (TOST p = 0.011 and 0.015) and directionally superior in a third; CTRC lost discovery power and bought no transport benefit. Under simulated platform shift all constructs degraded smoothly and comparably, with no rescue regime. Bulk-derived ligand–receptor scores transport weakly and construct-independently; future benchmarks should report formal equivalence rather than post hoc superiority claims.
Source: Research Square
Author: Ning Zhou
Institution: East China Normal University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225255457