Non-exonic read content reorganises lncRNA co-expression networks in renal and other cancers

Co-expression networks are used to find prognostic lncRNA programmes, but lncRNA quantification depends on unprocessed RNA in the library. In renal cancer (1,062 patients), the leading lncRNA axis tracked the non-exonic (non-feature) read fraction, a routine alignment metric, at Spearman rho 0.90. Without adjustment, most of the lncRNA network merged into one module. Adjustment preserved agreement with single-cell tumour-normal differences. Under rules fixed with the renal results known, 9 of 25 TCGA cancer types had a lncRNA-specific axis and 4 had network collapse (8 and 2 of 23 non-renal types). Intronic lncRNAs tracked the metric more than intergenic ones in all 25, and the metric was not consistently prognostic. All five renal modules that survived adjustment kept their direction in an external cohort, two nominally significant and none at a 5% false discovery rate. Three localised to malignant or epithelial cells. Together they added no discrimination over TNM and grade.