Letter to the editor: Serum S100A6 as complementary biomarker for pancreatic cancer-an advance needing clearer delineation

Table 2 Hypothetical stratification of carbohydrate antigen 19-9-false-negative pancreatic cancer patients by Lewis antigen status to interpret S100A6 complementarity

Subgroup of CA19-9 false-negative PC patients	Expected proportion	Hypothetical S100A6 positivity	Interpretation of complementarity
Lewis antigen-negative (cannot produce CA19-9)	5%-10% of general population1	Possibly high	S100A6 acts as a substitute, not a biological complement
Lewis antigen-positive (can produce CA19-9)	Remaining patients	Could be independent	True biological complementarity (different pathway)
Unknown (original study)	100%	41% (39/96)2	Cannot distinguish between the above two mechanisms

¹Prevalence of Lewis-negative (le/Le) genotype in most populations[2].

²Based on Bae et al[1], S100A6 positivity defined by Youden-index-derived cutoff (≥ 60.2 ng/mL).

This table presents hypothetical scenarios because Lewis antigen status was not assessed in the original study. The interpretation of complementarity depends on whether S100A6 positivity occurs predominantly in Lewis-negative individuals (substitution) or in Lewis-positive individuals (true biological complementarity). PC: Pancreatic cancer; CA19-9: Carbohydrate antigen 19-9.