Plasma growth differentiation factor 15 levels are more strongly associated with host physiological status than with tumor progression in colorectal cancer

Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine associated with aging, nutritional status, and malignancy. However, whether plasma GDF-15 primarily reflects tumor progression or host physiological status in colorectal cancer (CRC) remains unclear. Accordingly, we conducted an integrated analysis of 70 patients with CRC and 63 healthy individuals, evaluating plasma GDF-15 levels, tumor GDF-15 expression, and gut microbiota profiles. Plasma GDF-15 levels were significantly associated with age, serum albumin levels, nutritional impairment, and American Society of Anesthesiologists Physical Status classification. Although plasma GDF-15 levels were associated with depth of invasion, lymph node metastasis, and pathological stage in univariable analyses, these associations were no longer significant after adjustment for age and serum albumin. Tumor GDF-15 expression was not correlated with plasma GDF-15 levels or tumor progression-related variables. Gut microbiota analyses revealed differences in microbial diversity and phylum-level composition according to plasma GDF-15 levels, although part of these differences appeared to be influenced by age. Overall, plasma GDF-15 in CRC is more strongly associated with host physiological status, including age- and nutrition-related background factors, than with tumor progression. Plasma GDF-15 may therefore serve as a complementary biomarker reflecting systemic host vulnerability in CRC.