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

Table 1 Comparison of the original study’s “early-stage” cohort with an ideal screening population (asymptomatic stage I pancreatic cancer)

Characteristic	Original study “early” group (n = 149)	Ideal screening population (asymptomatic stage I)	Implication
TNM stage I	9 (6%)	100%	Results largely reflect stage II, not very early disease
TNM stage II	140 (94%)	0%	-
Symptom status	Mostly symptomatic (tertiary referral)	Asymptomatic	Unable to assess screening performance
Tumor size	Not reported, but stage II typically > 4 cm1	Usually ≤ 4 cm	Sensitivity for small tumors unknown

¹Based on general tumor, node, metastasis staging guidelines (stage II: T3–T4, tumor > 4 cm or extending beyond pancreas).

Data for the original study are from Bae et al[1]. The ideal screening population is defined as asymptomatic individuals with stage I pancreatic cancer detected through population-based screening programs; a scenario not represented in the original study. TNM: Tumor, node, metastasis.

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.