Triglyceride-glucose index in predicting gastric cancer prognosis: A need for caution

Abstract

Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. Accurate prognostic assessment, which is essential for enhancing overall survival (OS), currently depends on pathologic and clinical staging. This underscores the urgent need for reliable and real-time prognostic biomarkers. The triglyceride-glucose (TyG) index, a readily available marker of insulin resistance, has recently emerged as a potential prognostic tool in GC. Numerous studies have consistently shown a significant association between elevated TyG levels and inferior OS as well as progression-free survival. Despite these promising findings, several challenges must be addressed before the TyG index can be widely adopted in clinical practice. Firstly, the TyG index lacks cancer-specificity, reflecting broader metabolic disturbances commonly observed in conditions such as obesity, diabetes, and cardiovascular disease. This lack of specificity complicates its interpretation in oncological settings. Additionally, the cutoff values for TyG index vary across studies, hindering the establishment of a standardized threshold for clinical application. While the TyG index provides valuable insights into a patient's metabolic health, its limited cancer specificity necessitates cautious use when evaluating the prognosis of GC treatment.

Keywords: Gastric cancer; Glycolipid metabolism; Overall survival; Prognostic biomarker; Progression-free survival; Triglyceride-glucose index.

Figure 1

The triglyceride-glucose index, derived from fasting glucose and triglyceride levels, has emerged as a promising prognostic indicator for gastric cancer. Insulin resistance (IR) characterized by chronic hyperglycemia and hyperinsulinemia, modulates key signaling pathways including PI3K/Akt, NF-κB, and AMPK. The triglyceride-glucose (TyG) index may serve as an indirect marker of IR through these pathways, thereby playing a crucial role in various gastric cancer (GC) cell processes including proliferation, apoptosis, invasion, and metastasis. Elevated TyG levels have been correlated with improved overall survival and progression-free survival in GC patients. However, several limitations restrict its broader application, including its lack of cancer specificity, inconsistent cutoff values across studies, and the poorly understood mechanisms by which IR influences cancer progression. This article highlights the necessity of a multifactorial approach to enhance prognostic accuracy and guide personalized treatment strategies. Future research is imperative to validate the clinical utility of the TyG index and investigate its integration with other biomarkers to optimize patient outcomes in GC. TyG: Triglyceride-glucose; OS: Overall survival; PFS: Progression-free survival.