Petrusel Livia, Rusu Ioana, Leucuta Daniel Corneliu, Seicean Radu, Suharoschi Ramona, Zamfir Paula, Seicean Andrada
Department of Gastroenterology, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania.
Department of Pathology, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca 400162, Romania.
World J Gastrointest Oncol. 2019 Dec 15;11(12):1126-1140. doi: 10.4251/wjgo.v11.i12.1126.
Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma (PDAC). The rapid disease progression and patient deterioration seems related to perineural invasion, but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied. As perineural invasion is difficult to be highlighted, a biomarker such as the neurotrophic factor Midkine (MK) which promotes the neuronal differentiation and the cell migration could be helpful. Also, Activin (ACV) has been described as cachexia related to PDAC. However, their role for assessing and predicting the disease course in daily practice is not known.
To assess the relationship between perineural invasion and cachexia and their biomarkers, MK and ACV, respectively, and their prognostic value.
This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies. Patients with other causes of malnutrition were excluded. The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data. These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease.
The study comprised 114 patients with PDAC, 125 controls and a supplementary group of 14 benign pancreatic tissue samples. ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls (63% 32% for ACV, < 0.001; 47% 16% for MK, < 0.001), with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage ( = 0.006), the presence of metastasis ( = 0.04), perineural invasion ( = 0.03) and diabetes ( = 0.002), but with no influence on survival. No correlation between clinicopathological factors and ACV expression was noted. Cachexia, present in 19% of patients, was unrelated to ACV or MK level. Higher ACV expression was associated with a shorter survival ( = 0.008).
The MK was a biomarker of perineural invasion, associated with tumor stage and diabetes, but without prognostic value as ACV. Cachexia was unrelated to perineural invasion, ACV level or survival.
恶病质导致胰腺腺癌（PDAC）患者生活质量低下。疾病的快速进展和患者病情恶化似乎与神经周围侵犯有关，但恶病质与神经周围侵犯在疾病进展中的关系鲜有研究。由于神经周围侵犯难以凸显，一种生物标志物，如促进神经元分化和细胞迁移的神经营养因子中期因子（MK）可能会有所帮助。此外，激活素（ACV）已被描述为与PDAC相关的恶病质。然而，它们在日常实践中评估和预测疾病进程的作用尚不清楚。
分别评估神经周围侵犯与恶病质及其生物标志物MK和ACV之间的关系及其预后价值。
本研究前瞻性纳入了经证实患有腺癌的患者以及一组匹配的无任何恶性肿瘤的对照组。排除有其他营养不良原因的患者。采用蛋白质印迹法分析ACV和MK的血浆水平，并将其与临床病理特征和生存数据相关联。这些结果通过对本研究中纳入患者的胰腺肿瘤组织以及一组来自良性疾病患者的手术切除标本的补充组进行免疫组织化学分析得以验证。
该研究包括114例PDAC患者、125例对照组以及一组14个良性胰腺组织样本的补充组。与对照组相比，ACV和MK在PDAC患者血浆中的过表达更为频繁（ACV为63%对32%，P<0.001；MK为47%对16%，P<0.001），胰腺组织中的水平相似。MK蛋白表达与临床晚期（P=0.006）、转移的存在（P=0.04）、神经周围侵犯（P=0.03）和糖尿病（P=0.002）密切相关，但对生存无影响。未发现临床病理因素与ACV表达之间存在相关性。19%的患者存在恶病质，与ACV或MK水平无关。ACV表达较高与较短的生存期相关（P=0.008）。
MK是神经周围侵犯的生物标志物，与肿瘤分期和糖尿病相关，但与ACV不同，无预后价值。恶病质与神经周围侵犯、ACV水平或生存无关。
