The triglyceride-glucose index shows promise as a novel prognostic marker for advanced hepatocellular carcinoma

Abstract

This commentary critically appraises the study by Li et al which pioneered the exploration of the triglyceride-glucose (TyG) index as a prognostic marker in hepatitis B virus-related advanced hepatocellular carcinoma patients undergoing combined camrelizumab and lenvatinib therapy. While we acknowledge the study’s clinical relevance in proposing an easily accessible metabolic biomarker, we delve into the mechanistic plausibility linking insulin resistance to immunotherapy response and angiogenic inhibition. We further critically examine the methodological limitations, including the retrospective design, the population-specific TyG cut-off value, and unaddressed metabolic confounders. We highlight the imperative for future research to validate its utility across diverse etiologies and treatment settings, and to unravel the underlying immunometabolic pathways.

Key Words: Triglyceride-glucose index; Prognostic marker; Advanced hepatocellular carcinoma; Camrelizumab; Lenvatinib

Core Tip: This commentary highlights triglyceride-glucose (TyG) index as a prognostic marker for hepatitis B virus-related advanced hepatocellular carcinoma on camrelizumab-lenvatinib. Low TyG (< 1.58) boosts survival, it’s an independent predictor, with limitations needing multicenter studies.

TO THE EDITOR

Hepatocellular carcinoma (HCC) ranks as the sixth most common malignant tumor and the third leading cause of cancer-related deaths worldwide[1]. Clinically, it faces the dual challenges of difficult prognostic assessment and difficult formulation of personalized treatment plans, particularly in patients with hepatitis B virus (HBV)-related HCC[2]. In recent years, combination regimens of immunotherapy and targeted therapy (e.g., camrelizumab combined with lenvatinib) have become an important treatment option for advanced HCC[3,4]. However, nearly half of patients still have unsatisfactory prognosis due to poor treatment response or adverse reactions. Therefore, identifying simple and reliable prognostic biomarkers has become a key demand in current clinical research on HCC.

The triglyceride-glucose (TyG) index is a novel, accessible marker of insulin resistance. Research reports suggest that insulin resistance may be related to multiple pathological mechanisms of tumors, including metabolism, immunity and angiogenesis. Interleukin-6 secreted by tumor cells can induce insulin resistance, promote a pro-inflammatory state, and support tumor progression[5]. In addition to the TyG index, several other prognostic markers have been established in HCC, including the alpha fetoprotein, albumin-bilirubin (ALBI) grade, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Compared to these indices, the TyG index offers a distinct advantage by reflecting underlying metabolic dysfunction and insulin resistance, which are increasingly recognized as key drivers of tumor progression and treatment resistance. While ALBI focuses on hepatic synthetic function, and NLR/PLR highlight inflammatory status, the TyG index integrates lipid and glucose metabolism. A direct comparative analysis in future research is essential to determine the incremental predictive value and potential clinical superiority of TyG within the prognostic toolkit for HCC.

Insulin resistance is often accompanied by hyperglycemia and hyperinsulinemia. Hyperglycemia and hyperinsulinemia affect the activation and function of immune cells by promoting tumor growth and chronic inflammation, thereby influencing the anti-tumor immune response. The number of macrophages in the tumor tissues of diabetic patients increases, and they tend to exhibit an M2 (immunosuppressive) phenotype[6]. Insulin receptors are highly expressed in both normal and cancer-derived endothelial cells[7]. And the activation of these receptors is related to cell migration, proliferation, endothelial survival and vascular endothelial growth factor expression during the process of tumor angiogenesis. When insulin resistance occurs, the body compensates by secreting more insulin. High insulin levels can activate the signaling pathways related to angiogenesis. Therefore, insulin resistance promotes tumor angiogenesis through multiple mechanisms and increases the risk of tumor occurrence and development[8].

As a metabolic marker based on routine blood test indicators, the TyG index has been proven to effectively reflect the state of insulin resistance[9] and is closely associated with the progression and prognosis of various malignant tumors, such as colorectal cancer and breast cancer[10,11]. Nevertheless, the prognostic value of the TyG index remains unclear in the context of HBV-related advanced HCC patients receiving combination regimens of immunotherapy and targeted therapy.

CONCLUSION

Against this backdrop, Li et al[11] conducted a retrospective analysis to explore the prognostic value of the TyG index in patients treated with camrelizumab combined with lenvatinib. The study included 278 patients with B/C stage HBV-related HCC who were admitted to the Affiliated Hospital of Xuzhou Medical University from December 2020 to December 2023.

ACKNOWLEDGEMENTS

We sincerely appreciate all the support and collaboration from our colleagues in the Chinese People’s Liberation Army General Hospital.