Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass

Hogendorf, Piotr; Durczyński, Adam; Skulimowski, Aleksander; Kumor, Anna; Poznańska, Grażyna; Strzelczyk, Janusz

doi:10.3233/cbm-170203

Cited by 25 publications

(20 citation statements)

References 31 publications

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“…Twelve diagnostic studies [12, 13, 15–24], comprising 2380 patients and 4630 paired controls, were included in the diagnostic meta-analysis. The study participants involved included Chinese [12, 13, 16, 20, 21, 23, 24], Australian [17, 19, 22], American [18], Polish [20], and Spanish [15] patients, with sample sizes ranging from 42 to 807. The types of DST covered in these studies included colorectal cancer (CRC) [8–13], gastrointestinal cancer (GC) [14, 15], pancreatic cancer (PC) [16–19], esophageal carcinoma (EC) [21, 22], and liver cancer [23, 24], of which the final diagnoses were all confirmed histologically by surgical operation.…”

Section: Resultsmentioning

confidence: 99%

“…Intriguingly, GDF-15 levels are substantially increased in various pathological conditions, including inflammation and injury [5–7]. Notably, experimental and epidemiological evidence has demonstrated that GDF-15 levels are up-regulated in many types of DST, such as colorectal cancer (CRC) [8–13], gastrointestinal cancer (GC) [14, 15], pancreatic cancer (PC) [16–20], esophageal carcinoma (EC) [21, 22], and liver cancer [23, 24]. Recently, GDF-15 has received much attention as a diagnostic and prognostic biomarker in DST.…”

Section: Introductionmentioning

confidence: 99%

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Appraising growth differentiation factor 15 as a promising biomarker in digestive system tumors: a meta-analysis

Wang

Jiang

et al. 2019

BMC Cancer

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Background Previous studies have highlighted cytokine growth differentiation factor 15 (GDF-15) as a potential biomarker for digestive system tumors (DST). This study sought to assess the feasibility of using GDF-15 as a diagnostic and prognostic biomarker in DST. Methods Eligible studies from multiple online databases were reviewed. Meta-analyses of diagnostic parameters were carried out using standard statistical methods. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the relationship between GDF-15 levels and clinical prognosis. Results We identified 17 eligible studies comprising 3966 patients with DST. The sensitivity, specificity, and area under the curve (AUC) for the discriminative performance of GDF-15 as a diagnostic biomarker were 0.74 (95% CI: 0.68–0.80), 0.83 (95% CI: 0.75–0.89), and 0.84, respectively. Moreover, increased GDF-15 expression levels were markedly associated with unfavorable overall survival (OS) in patients with DST (HR = 2.34, 95% CI: 2.03–2.70, P < 0.001; I 2 = 0.0%) and colorectal cancer (CRC) (HR = 2.27, 95% CI: 1.96–2.63, P < 0.001; I 2 = 0.0%). Stratification by cancer type, test matrix, ethnicity, and cut-off setting also illustrated the robustness of the diagnostic value of GDF-15 in DST. Conclusion Collectively, our data suggest that GDF-15 expression level may have value as a diagnostic and prognostic biomarker, independent of other, traditional biomarkers. Electronic supplementary material The online version of this article (10.1186/s12885-019-5385-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Appraising growth differentiation factor 15 as a promising biomarker in digestive system tumors: a meta-analysis

Wang

Jiang

et al. 2019

BMC Cancer

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“…Interestingly, another member of the family GDF15 is directly correlated with poor survival in PC patients, and it is proposed as a better marker than CA-125 (66), again raising the atypical functions of this growth factor.…”

Section: Pancreatic Cancermentioning

confidence: 99%

GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies

et al. 2019

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Growth Differentiation Factor 11 (GDF11), a member of the super family of the Transforming Growth Factor β, has gained more attention in the last few years due to numerous reports regarding its functions in other systems, which are different to those related to differentiation and embryonic development, such as age-related muscle dysfunction, skin biology, metabolism, and cancer. GDF11 is expressed in many tissues, including skeletal muscle, pancreas, kidney, nervous system, and retina, among others. GDF11 circulating levels and protein content in tissues are quite variable and are affected by pathological conditions or age. Although, GDF11 biology had a lot of controversies, must of them are only misunderstandings regarding the variability of its responses, which are independent of the tissue, grade of cellular differentiation or pathologies. A blunt fact regarding GDF11 biology is that its target cells have stemness feature, a property that could be found in certain adult cells in health and in disease, such as cancer cells. This review is focused to present and analyze the recent findings in the emerging research field of GDF11 function in cancer and metabolism, and discusses the controversies surrounding the biology of this atypical growth factor.

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“…As a member of the transforming growth factor (TGF)-β subfamily, growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine associated with various diseases such as cancers [ 1 , 2 , 3 , 4 , 5 ], cardiovascular disorders [ 6 ], mitochondrial disorders [ 7 ], hyperthyroidism [ 8 ], obesity and type 2 diabetes [ 9 ]. GDF-15 mediates food intake, energy consumption, and body weight [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Expression of GDF-15 is maintained at low levels in most tissues [ 21 ] and is increased by p53 activation due to various cellular stressors, such as inflammation, oxidative stress, hypoxia, and oncogene activation [ 22 ]. Serum GDF-15 levels in the patients with chronic pancreatitis were higher, 2248 pg/mL in mean [ 1 ] compared to healthy subjects (416.8 pg/mL [ 23 ], 546 [ 24 ], 639 [ 25 ] in mean). Pancreatic disease compressing the pancreatic duct is considered to increase the GDF-15 level, and thus can result from benign pancreatic diseases including chronic pancreatitis, intraductal papillary mucinous tumor, and serous cystic tumor.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

Suzuki

Mitsunaga

Ikeda

et al. 2021

Cancers

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We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

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Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass

Cited by 25 publications

References 31 publications

Appraising growth differentiation factor 15 as a promising biomarker in digestive system tumors: a meta-analysis

Appraising growth differentiation factor 15 as a promising biomarker in digestive system tumors: a meta-analysis

GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer

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