Serum insulin-like growth factor binding protein 2 levels as biomarker for pancreatic ductal adenocarcinoma-associated malnutrition and muscle wasting.
Serum insulin-like growth factor binding protein 2 levels as biomarker for pancreatic ductal adenocarcinoma-associated malnutrition and muscle wasting.
复制标题
血清胰岛素样生长因子结合蛋白 2 水平作为胰腺导管腺癌相关营养不良和肌肉萎缩的生物标志物。
DOI：
10.1002/jcsm.12692
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Dong J;Yu J;Li Z;Gao S;Wang H;Yang S;Wu L;Lan C;Zhao T;Gao C;Liu Z;Wang X;Hao J
营养不良和肌肉萎缩是患有癌症恶病质的胰腺导管腺癌 (PDAC) 患者中经常观察到的常见特征。它们与生存率和生活质量降低有关。营养治疗是 PDAC 多模式癌症护理的重要组成部分。但由于营养评估的复杂性，目前只有30%~60%的营养风险患者接受了营养治疗。确定可用于改善 PDAC 相关营养不良管理的生物标志物非常重要。血清胰岛素样生长因子结合蛋白 2 (IGFBP2) 已成为多种肿瘤的潜在血清生物标志物。然而，其与 PDAC 营养不良和肌肉萎缩的关系尚不清楚。我们采用免疫组织化学和酶联免疫吸附试验评估了98例PDAC患者的肿瘤IGFBP2表达和血清IGFBP2水平，并分析了它们之间的相关性。此外，我们还探讨了肿瘤和血清中的 IGFBP2 与营养状况（患者主观整体评估和骨骼肌指数）之间的关系。将 Pan02 IGFBP2 稳定转染细胞系、Pan02 PLV-IGFBP2 细胞和 PLKO-IGFBP2 细胞皮下注射到 C57BL/6 小鼠的胁腹中。测量了这些小鼠的血清 IGFBP2 水平、食物摄入量和体重。肌肉萎缩的程度通过苏木精和伊红、油红O和马森三色染色来表征。测量了几种重要的肌肉相关信号蛋白（例如 atrogin-1 和肌肉 RING Finger 1）的 mRNA 和蛋白表达。在 98 名患者中，我们发现肿瘤 IGFBP2 表达与血浆 IGFBP2 水平相关（rs = 0.562，P < 0.001），并且在患者主观总体评估≥9 的患者中显着增加，并与总生存期相关。此外，血清IGFBP2水平与骨骼肌指数（rs = -0.600，P < 0.001）和Hounsfield单位（rs = -0.532，P < 0.001）呈负相关。与 Pan02 PLV-对照组相比，注射 Pan02 PLV-IGFBP2 细胞的小鼠循环 IGFBP2 升高，而体重和食物摄入量降低。这些小鼠还表现出明显加重的肌纤维萎缩、脂质沉积和胶原组织增加，腓肠肌中atrogin-1和肌肉RING Finger 1的mRNA和蛋白表达增加。相反，PLKO-IGFBP2 组的这些症状得到缓解。在目前的研究中，PDAC中血清IGFBP2水平、营养不良和肌肉萎缩之间存在显着相关性。我们的结果表明，血清 IGFBP2 水平可能是 PDAC 相关严重营养不良和肌肉萎缩的一个有前途的生物标志物和干预目标。
Malnutrition and muscle wasting are common features frequently observed in pancreatic ductal adenocarcinoma (PDAC) patients with cancer cachexia. They are associated with reduced survival and quality of life. Nutrition therapy is an important part of multimodal cancer care in PDAC. However, due to the complexity of nutrition assessment, only 30–60% of patients with nutritional risks receive nutritional treatment at present. It is important to identify biomarkers that may be used to improve management of PDAC‐associated malnutrition. Serum insulin‐like growth factor binding protein 2 (IGFBP2) has emerged as a potential serum biomarker in a variety of tumours. However, its association with malnutrition and muscle wasting in PDAC is unclear. We evaluated the tumour IGFBP2 expression and serum IGFBP2 level in 98 PDAC patients using immunohistochemistry and enzyme‐linked immunosorbent assay and analysed the correlation between them. Furthermore, we explored the relationship between IGFBP2 of both tumour and serum and nutritional status (Patient‐Generated Subjective Global Assessment and skeletal muscle index). Pan02 IGFBP2 stable transfection cell lines, Pan02 PLV‐IGFBP2 cells, and PLKO‐IGFBP2 cells were injected subcutaneously into the flank of C57BL/6 mouse. Serum IGFBP2 levels, food intake, and body weight of these mice were measured. The degree of muscle atrophy is characterized by haematoxylin and eosin, Oil Red O, and Masson's trichrome staining. The mRNA and protein expression of several essential muscle‐related signal proteins such as atrogin‐1 and muscle RING finger 1 was measured. Among 98 patients, we found that tumour IGFBP2 expression is related to plasma IGFBP2 levels (r s = 0.562, P < 0.001), and they significantly increased among patients with Patient‐Generated Subjective Global Assessment ≥9 and correlated with overall survival. Moreover, serum IGFBP2 level is negatively correlated with skeletal muscle index (r s = −0.600, P < 0.001) and Hounsfield units (r s = −0.532, P < 0.001). In mice injected with Pan02 PLV‐IGFBP2 cell, circulating IGFBP2 was elevated while body weight and food intake were decreased when compared with Pan02 PLV‐Control group. These mice also exhibited significantly aggravated muscle fibre atrophy, lipid deposition, and increased collagen tissue, and the expression of mRNA and protein of atrogin‐1 and muscle RING finger 1 in the gastrocnemius muscle is increased. Conversely, these symptoms were alleviated in the PLKO‐IGFBP2 group. In the current study, there is a significant correlation between serum IGFBP2 levels, malnutrition, and muscle atrophy in PDAC. Our results suggested that serum IGFBP2 level might be a promising biomarker and intervention targets for PDAC‐associated severe malnutrition and muscle wasting.
登录
查看更多内容
DOI：
10.1080/01635581.2012.670743
发表时间：
2012-01-01
影响因子：
2.9
作者：
Attar, A.;Malka, D.;Taieb, J.
通讯作者：
Taieb, J.
影响因子：
5.8
作者：
Liou, Jyh-Ming;Shun, Chia-Tung;Lin, Jaw-Town
通讯作者：
Lin, Jaw-Town
DOI：
10.1186/s13046-016-0317-z
发表时间：
2016-03-15
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Huang XY;Huang ZL;Yang JH;Xu YH;Sun JS;Zheng Q;Wei C;Song W;Yuan Z
通讯作者：
Yuan Z
影响因子：
2.9
作者：
Kendrick, Zachary W.;Firpo, Matthew A.;Mulvihill, Sean J.
通讯作者：
Mulvihill, Sean J.
影响因子：
3.7
作者：
Choi Y;Oh DY;Kim TY;Lee KH;Han SW;Im SA;Kim TY;Bang YJ
通讯作者：
Bang YJ