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Titin is a giant protein found in striated muscle, and its degradation product, the N-terminal fragment of titin (N-Titin), has attracted attention as a biomarker of muscle injury. To date, most clinical studies have evaluated urinary N-Titin using creatinine-corrected values (pmol/mg Cr), whereas the clinical significance of serum N-Titin has remained largely unclear.

A research group led by Professor Mitsugi Shimoda of the Department of Gastrointestinal Surgery, Tokyo Medical University Ibaraki Medical Center, investigated the relationship between preoperative serum and urinary N-Titin levels in patients with gastrointestinal malignancies (GIM). In this study, 104 patients undergoing surgery for GIM were enrolled. Blood and urine samples were collected before surgery, and N-Titin levels were measured simultaneously. In addition, associations between N-Titin levels and body composition parameters were evaluated.

Study Population
- Hepatobiliary-pancreatic malignancies (HPBMs): 42 patients
- Colorectal malignancies (CRMs): 36 patients
- Upper gastrointestinal malignancies (UGIMs): 26 patients
The study cohort comprised 76 men and 28 women, with a median age of 68 years.

Key Findings
A strong positive correlation was observed between serum N-Titin (pmol/L) and urinary N-Titin (pmol/mg Cr) levels (r = 0.78, P < 0.001).
Furthermore, both biomarkers showed similar correlation patterns with body composition parameters. Serum and urinary N-Titin levels demonstrated weak negative correlations with percent body fat (PBF), fat mass index (FMI), and phase angle (PhA), and weak positive correlations with the extracellular water/total body water ratio (ECW/TBW) and age. Neither serum N-Titin nor urinary N-Titin showed a significant correlation with skeletal muscle mass index (SMI).
These findings suggest that serum and urinary N-Titin may reflect similar biological processes in patients with GIM. In addition, the lack of correlation with SMI suggests that N-Titin may reflect muscle fiber degradation, muscle damage, or muscle condition rather than muscle mass itself.

Clinical Significance
This study demonstrated a strong correlation between serum and urinary N-Titin levels in patients with gastrointestinal malignancies. The findings suggest that N-Titin assessment, which has traditionally been performed using urine samples, may also be feasible using blood samples.
Unlike urinary N-Titin, serum N-Titin does not require creatinine correction. The authors also discuss its potential applicability in patients for whom urinary evaluation may be difficult, including those receiving dialysis or those with impaired renal function.

Future Perspectives
Serum N-Titin may become a novel biomarker for assessing muscle injury and perioperative risk in patients with gastrointestinal malignancies. Further studies are needed to investigate its relationship with sarcopenia and malnutrition, as well as its association with postoperative complications and long-term outcomes. Such investigations are expected to further clarify the clinical significance of serum N-Titin.


Please refer to the following publication for more details.

Mitsugi Shimoda et al.
Comparison of preoperative urinary Titin levels and serum Titin levels in patients with gastrointestinal malignancy
J Gastrointest Oncol. 2026;17(3):146.


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