Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma
Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma
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DOI：
10.1002/cncr.20972
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发表时间：
2005-05-01
期刊：
影响因子：
6.2
通讯作者：
Fearon, KCH
中科院分区：
文献类型：
--
作者：
Deans, C;Wigmore, S;Fearon, KCH
背景甲状旁腺素相关肽（PTHrP）是一种肿瘤源性循环因子，与恶性肿瘤的高钙血症有关。PTHrP作为预后指标的作用尚不清楚。研究表明，它可能作为一种生长因子的功能，最近，PTHrP诱导细胞因子表达的能力已被描述。PTHrP也被认为是一种前趋化因子。在这项研究中，作者研究了PTHrP在无高钙血症的胃食管癌患者中的预后价值，并确定PTHrP是否与全身炎症和不良营养状态相关。在诊断时招募患者。收集血清用于测定c-末端片段PTHrP（cPTHrP）水平（通过放射免疫测定法）和钙水平以及血清细胞因子和急性时相蛋白水平（通过酶联免疫吸附测定法）。在收集血清的同时对患者进行营养评估。患者接受常规分期，并记录生存时间。151例食管胃癌患者被招募。151例患者中有6例（4.0%）患者出现高钙血症，26例（17.2%）患者血清cPTHrP水平升高。cPTHrP水平与血清钙浓度（P = 0.72）或不良营养状态之间无相关性。然而，升高的cPTHrP与显著较高的血清可溶性肿瘤坏死因子受体水平（P = 0.008）和显著较低的转铁蛋白（P = 0.009）和白蛋白（P = 0.02）水平相关。与C相关蛋白水平也存在弱相关性（P = 0.06）。单变量分析显示，cPTHrP水平升高与不良预后相关，这是通过生存期缩短来确定的（P = 0.038），但未进行多变量分析（P = 0.15）。血清cPTHrP水平升高存在于约17%的患者中，在无高钙血症的胃食管癌患者中，不良预后(c)2005年美国癌症协会。
BACKGROUND. Parathyroid hormone-related peptide (PTHrP) is a tumor-derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status.METHODS. Patients were recruited at the time of diagnosis. Serum was collected for determination of c-terminal fragment PTHrP (cPTHrP) levels (by radioimmunoassay) and calcium levels as well as levels of serum cytokines and acute-phase proteins (with an enzyme-linked immunosorbent assay). Nutritional assessment of patients was undertaken at the same time as serum collection. Patients underwent routine staging, and survival duration was recorded.RESULTS. One hundred fifty-one patients with esophagogastric carcinoma were recruited. Six of 151 patients (4.0%) patients were hypercalcemic, and 26 patients (17.2%) had elevated serum cPTHrP levels. There was no association between the cPTHrP level and either serum calcium concentrations (P = 0.72) or adverse nutritional status. Elevated cPTHrP, however, was associated with significantly higher serum levels of soluble tumor necrosis factor receptor (P = 0.008) and with significantly lower levels of transferrin (P = 0.009) and albumin (P = 0.02). There was also a weak association with C-related protein levels (P = 0.06). Elevated cPTHrP levels also were associated with an adverse prognosis, as determined by reduced survival duration, on univariate analysis (P = 0.038), but not on multivariate analysis (P = 0.15).CONCLUSIONS: Elevated serum cPTHrP levels were present in approximately 17% of patients with gastroesophageal carcinoma in the absence of hypercalcemia and was associated with markers of systemic inflammation and with an adverse prognosis. (c) 2005 American Cancer Society.