Interpreting CFH Expression Across Cancers: Why Resolving the Factor H–Like 1 Isoform Matters

1

Zheng et al. reported that CFH transcription was associated with tumour stage, survival, immune infiltration, tumour mutational burden, and microsatellite instability across cancers.
2

CFH encodes full-length factor H (FH) and the alternatively spliced factor H–like 1 (FHL-1), which has seven complement control protein domains and a distinctive short tail.
3

The study’s N-terminal qRT-PCR primers and shRNA constructs target sequences shared by FH and FHL-1, so they measure or suppress both isoforms.
4

FHL-1 is expressed in several tissues and tumour cells, and its extracellular matrix retention may give it distinct local effects on complement regulation.
5

The authors suggest that future biomarker studies use isoform-resolved methods, including splice-junction–specific qPCR, long-read RNA sequencing, or differentiating proteomic techniques.

1