Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer.
Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer.
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DOI：
10.3390/cancers13194842
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发表时间：
2021-09-28
期刊：
影响因子：
5.2
通讯作者：
Ochiai A
中科院分区：
文献类型：
--
作者：
Suzuki H;Mitsunaga S;Ikeda M;Aoyama T;Yoshizawa K;Yoshimatsu H;Kawai N;Masuda M;Miura T;Ochiai A
生长分化因子15 （GDF-15）是一种应激反应细胞因子，介导食物摄入、能量消耗和体重。我们旨在评估循环GDF-15水平是否与恶病质症状相关，包括晚期胰腺癌（APC）的骨骼肌质量减少、全身炎症反应、运动状态不佳、厌食、生存时间缩短和生物肿瘤活性。血清GDF-15的截止值为3356.6 pg/mL，作为良性胰腺疾病患者的平均值加上两个标准差。高血清GDF-15的APC患者表现出表现恶化、厌食、炎症和肿瘤负荷升高、恶病质特征以及肿瘤GDF-15产生途径中Akt和JNK的激活。本研究确定肿瘤驱动的GDF-15是APC恶病质症状的潜在原因。我们旨在评估循环生长分化因子15 （GDF-15）与晚期胰腺癌（APC）恶病质症状和生物活性的关系。Treatment-naïve回顾性分析APC肝转移或良性胰腺疾病患者。在抗癌治疗前收集肝转移的临床资料、血液样本和活检标本。采用酶联免疫吸附法和反相蛋白阵列法分别检测小鼠血清GDF-15水平和肝转移细胞裂解液中多种蛋白的表达。血清GDF-15的截止值确定为3356.6 pg/mL，为良性胰腺疾病的平均值加两个标准差。高gdf -15组表现为低Karnofsky性能状态（KPS） （p = 0.037），低Eastern Cooperative Oncology组性能状态（ECOG-PS） （p = 0.049），严重的食欲下降（p = 0.011），高血清碳水化合物抗原19-9 （p = 0.019）和c反应蛋白（p = 0.009）水平。高gdf -15组的肿瘤表达高水平的磷酸化JNK （p = 0.007）和pAkt （p = 0.040）。高血清GDF-15的APC患者表现出恶病质特征和肿瘤中涉及Akt和JNK的信号通路激活。本研究表明循环GDF-15可能与APC的病质症状有关。
Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine that mediates food intake, energy consumption, and body weight. We aimed to evaluate whether circulating GDF-15 level could be associated with cachexia symptoms, which include loss of skeletal muscle mass, systemic inflammatory reaction, poor performance status, anorexia, shortened survival time and biological tumor activity in advanced pancreatic cancer (APC). The cut-off for serum GDF-15 was 3356.6 pg/mL, as the mean plus two standard deviations in patients with benign pancreatic disease. APC patients with high serum GDF-15 showed worsened performance, anorexia and elevations of inflammatory and tumor burden, signatures of cachexia, and activation of Akt and JNK in tumor GDF-15-producing pathways. This study identified tumor-driven GDF-15 as a potential cause of cachexia symptoms in APC. 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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