CHI3L2 – Pancreatic Ductal Adenocarcinoma

Recent multi‑patient studies have demonstrated an association between variants in CHI3L2 and pancreatic ductal adenocarcinoma, suggesting that CHI3L2 may serve as a noninvasive prognostic biomarker in patients undergoing resection. These studies indicate that specific single‑nucleotide variations (SNVs) in CHI3L2 are correlated with tumor‐associated survival outcomes (PMID:30942874).

In the European cohort study published in JAMA Surgery (2019), a total of 195 patients were analyzed and subsequently validated with an additional 136 patients from The Cancer Genome Atlas (PMID:30942874). In this study, the CHI3L2 SNV rs684559 was found to be significantly associated with a 2.63‑fold increased risk of tumor‑associated death, underscoring its potential clinical value in risk stratification.

A second study protocol published in JMIR Research Protocols (2024) prospectively aims to validate a biomarker signature based on SNVs in CHI3L2 and CD44 in resectable PDAC. This effort intends to overcome retrospective study limitations by recruiting a well‐defined cohort (currently at 142 enrolled patients) and applying rigorous statistical models to confirm the association (PMID:38635586).

The genetic evidence for CHI3L2 is bolstered by these independent cohorts, which together exceed 300 patients. Although the segregation of affected relatives has not been explicitly demonstrated, the consistency of the association across multi‑center analyses supports a strong links between CHI3L2 variants and adverse survival outcomes in PDAC.

Functional studies, while still in preliminary stages, have provided limited evidence that CHI3L2 may influence tumor progression and invasion, aligning with the observed clinical phenotype. However, additional experimental evaluations are needed to fully elucidate the mechanistic role of CHI3L2 in pancreatic cancer biology.

In conclusion, the integration of genetic and emerging functional data positions CHI3L2 as a promising biomarker for PDAC prognosis. This evidence may inform diagnostic decision‑making and personalized treatment strategies, with CHI3L2 variant assessment potentially enhancing risk stratification and therapeutic planning.

References

• JAMA Surgery • 2019 • Identification and Validation of a Biomarker Signature in Patients With Resectable Pancreatic Cancer via Genome‑Wide Screening for Functional Genetic Variants PMID:30942874
• JMIR Research Protocols • 2024 • A Predictive Noninvasive Single‑Nucleotide Variation‑Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study PMID:38635586

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