胰腺癌患者中甲状旁腺激素相关蛋白（PTHrP）与明显的疾病进展及宿主组织消耗体征

Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting.

作者信息

Iresjö Britt-Marie, Kir Serkan, Lundholm Kent

机构信息

Surgical Metabolic Research Lab, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden.

Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Molecular Biology and Genetics, KoÇ University, Istanbul 34450, Turkey.

出版信息

Transl Oncol. 2023 Oct;36:101752. doi: 10.1016/j.tranon.2023.101752. Epub 2023 Aug 2.

DOI:10.1016/j.tranon.2023.101752

PMID:37540958

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10407952/

Abstract

BACKGROUND

Cancer-cachexia is a complex syndrome secondary to physiological mechanisms related to classical hormone and immune alterations, where contributions of neuro-endocrine involvement have been less evaluated. Therefore, the aim of our study was to explore relationships between PTHrP and whole body metabolism in patients with progressive pancreatic carcinoma; relevant to "fat tissue browning".

METHODS

Patient serum samples and clinical information were retrieved from earlier translational projects (1995-2005), at Sahlgrenska University Hospital in Gothenburg. Blood PTHrP levels were determined at Harvard medical School (2014). Patient data included: medical history, clinical laboratory tests, food diaries, resting metabolic expenditure, body composition, exercise capacity, Health-Related Quality of Life (SF-36) and mental disorders (HAD-scales).

RESULTS

Serum PTHrP was detectable in 17 % of all samples without significance to tumor stage. PTHrP-negativity at inclusion remained during follow-up. Mean PTHrP concentration was 262±274 pg/ml, without sex difference and elevation over time. PTHrP-positive and negative patients experienced similar body weight loss (%) at inclusion, with a trend to deviate at follow ups (16.8±8.2% vs. 13.1±8.2%, p<0.06), where PTHrP concentrations showed correlations to weight loss, handgrip strength and Karnofsky performance, without difference in exercise capacity. PTHrP-positivity was related to increased whole body fat oxidation (p<0.006-0.01) and reduced carbohydrate oxidation (p<0.01-0.03), independently of peripheral lipolysis. Metabolic alterations in PTHrP-positive patients were related to reduced Health Related Quality of life (SF: p<0.08, MH: p<0.02), and increased anxiety and depression (HAD 1-7: p<0.004; HAD 8-14: p<0.008).

CONCLUSION

Serum PTHrP positivity in patients with pancreatic carcinoma was related to altered whole body oxidative metabolism; perhaps induced by "browning" of fat cells?

摘要

背景

癌症恶病质是一种继发于与经典激素和免疫改变相关的生理机制的复杂综合征，其中神经内分泌参与的作用评估较少。因此，我们研究的目的是探讨甲状旁腺激素相关蛋白（PTHrP）与进展期胰腺癌患者全身代谢之间的关系；这与“脂肪组织褐变”相关。

方法

从哥德堡萨尔格伦斯卡大学医院早期的转化项目（1995 - 2005年）中获取患者血清样本和临床信息。2014年在哈佛医学院测定血PTHrP水平。患者数据包括：病史、临床实验室检查、饮食日记、静息代谢消耗、身体成分、运动能力、健康相关生活质量（SF - 36）和精神障碍（HAD量表）。

结果

在所有样本中，17%可检测到血清PTHrP，与肿瘤分期无关。纳入时PTHrP阴性在随访期间保持不变。PTHrP平均浓度为262±274 pg/ml，无性别差异且随时间无升高。PTHrP阳性和阴性患者在纳入时体重减轻百分比相似，随访时有偏离趋势（16.8±8.2%对13.1±8.2%，p<0.06），其中PTHrP浓度与体重减轻、握力和卡氏评分相关，运动能力无差异。PTHrP阳性与全身脂肪氧化增加（p<0.006 - 0.01）和碳水化合物氧化减少（p<0.01 - 0.03）相关，与外周脂肪分解无关。PTHrP阳性患者的代谢改变与健康相关生活质量降低（SF：p<0.08，MH：p<0.02）以及焦虑和抑郁增加（HAD 1 - 7：p<0.004；HAD 8 - 14：p<0.008）相关。