Ni CX, Xu JJ. Letter to the editor: Serum S100A6 as complementary biomarker for pancreatic cancer-an advance needing clearer delineation. World J Gastroenterol 2026; 32(41): 123870 [DOI: 10.3748/wjg.123870]
Corresponding Author of This Article
Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an City Central Hospital, No. 29 Longtan Road, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
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Oncology
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letter
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Ni CX, Xu JJ. Letter to the editor: Serum S100A6 as complementary biomarker for pancreatic cancer-an advance needing clearer delineation. World J Gastroenterol 2026; 32(41): 123870 [DOI: 10.3748/wjg.123870]
World J Gastroenterol. Nov 7, 2026; 32(41): 123870 Published online Nov 7, 2026. doi: 10.3748/wjg.123870
Letter to the editor: Serum S100A6 as complementary biomarker for pancreatic cancer-an advance needing clearer delineation
Chun-Xiao Ni, Jia-Ju Xu
Chun-Xiao Ni, Department of Minimally Invasive Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Jia-Ju Xu, Department of Medical Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Co-first authors: Chun-Xiao Ni and Jia-Ju Xu.
Author contributions: Ni CX and Xu JJ performed the writing, editing, and literature review, contributed equally to this work, thus qualified as the co-first authors of the paper; Xu JJ was responsible for the conceptualization, methodology, and supervision; all authors approved the final version.
AI contribution statement: DeepSeek was used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Jia-Ju Xu, MD, Department of Medical Oncology, Tai’an City Central Hospital, No. 29 Longtan Road, Tai’an 271000, Shandong Province, China. jiajuxu1101@163.com
Received: June 1, 2026 Revised: June 15, 2026 Accepted: August 10, 2026 Published online: November 7, 2026 Processing time: 106 Days and 23 Hours
Abstract
The study by Bae et al was the first prospective study to evaluate serum S100A6 as a tumor marker for early detection of pancreatic cancer (PC). The study was commendably well designed, included 414 patients, underwent bootstrap validation, and demonstrated that adding S100A6 to CA19-9 and CEA enhanced detection of early PC compared with chronic pancreatitis (area under the curve = 0.821, P = 0.017). However, some issues need more exploration. The “early stage” group is composed of 140 stage II tumors and 9 stage I cases; thus, the results apply mainly to resectable PC, not stage I disease. Second, Lewis antigen status for second malignancy cases is not available, and it is unclear whether Lewis-negative cases are present in CA19-9–negative/S100A6–positive cases (41% of CA19-9 false negatives) or constitute a distinct subgroup. Third, the study was a single-center using samples from 2008 to 2015; so multicenter validation is needed. Fourth, the mechanism by which S100A6 enters the circulation needs detailed study. Fifth, clinical net benefit needs assessment using decision curve analysis. Collectively, there is evidence for serum S100A6 as a complementary biomarker for PC, but outstanding questions must be resolved before the marker can be used clinically.
Core Tip: This letter commends the innovative study by Bae et al as the first large prospective study evaluating serum S100A6 for early detection of pancreatic cancer, and outlines five points requiring attention. The “early-stage” group consists predominantly of stage II; absence of Lewis antigen status information limits mechanistic understanding of S100A6’s complementary role; single center design and use of historical samples limit generalizability; absence of decision curve analysis means net benefit is unassessed; and how S100A6 enters the circulation is unidentified. Overall, serum S100A6 is promising, but these limitations must be addressed before clinical implementation.
