Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer

Abstract

Background:Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).Methods:Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.Results:Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).Conclusion:Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways

“…In oral and colorectal cancers, several reports have similarly shown that a high expression of GDF15 shown by immunohistochemistry was associated with many tumorigenic factors. 30,43 These data indicate that GDF15 in the cancer microenvironment might serve as a factor of the tumor progression of human ESCC.…”

“…43 A similar upregulation of GDF15 immunoreactivity was also reported in adenocarcinomas including colorectal, gastric, and prostate cancers. 30,34,44 Wang et al 42 also indicated that positive staining of GDF15 in ESCC tissues was mostly confined to the cytoplasm of ESCC cells with a diffuse pattern. In the present study too, the GDF15-positive cells in the ESCC tissues were mostly confined to the cytoplasm of ESCC cells, whereas GDF15 immunoreactions were detected in other stromal cells such as erythrocytes and macrophages.…”

“…28,29 In cancer, GDF15 overexpression has been described in colorectal cancer and malignant glioma. 19,30 In addition, serum GDF15 levels have been reported to be raised in patients with malignant glioma, pancreatic, or prostate carcinoma compared with those of healthy controls. 19,31,32 These previous findings may indicate that GDF15 exerts heterogeneous functions in tumors.…”

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

“…165 GDF-15 has been investigated in other cancers, and high plasma levels correlated with reduced time to recurrence and reduced overall survival in colorectal cancer. 216 In ovarian cancer high level of GDF-15 in ascites was an independent predictor of poor survival 121 , and preoperative plasma levels an independent predictor of poor survival. 123 We have shown GDF-15 as an independent predictor of lymph node metastasis (Paper III).…”

Role of GDF15 in radiosensitivity of breast cancer cells

“…GDF15 is published as a prognostic biomarker in ovarian cancer [1], a marker for tumor recurrence in colorectal cancer [2], and a novel serum marker for metastasis in uveal melanoma [3]. GDF15 expression is rapidly induced by a variety of cellular stresses in a p53-dependent and -independent manner, and it mediates cell cycle arrest and apoptosis in response to DNA damage, toxins, anoxia, liver injury, and other cellular stresses in different models [4][5][6].…”