Belltall Amparo, Mazzinari Guido, Garrido-Cano Iris, Giner Francisco, Marí Anabel Marqués, Eroles Pilar, Argente-Navarro María Pilar, Cata Juan Pablo, Diaz-Cambronero Oscar
Research Group in Perioperative Medicine, Hospital Universitario y Politécnico la Fe, Valencia, Spain.
Department of Anaesthesiology, Hospital Universitario y Politécnico la Fe, Valencia, Spain.
Front Oncol. 2022 Apr 6;12:801714. doi: 10.3389/fonc.2022.801714. eCollection 2022.
There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC).
Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx).
There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence.
In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an analysis of samples from the TCGA-GTEx database.
围手术期麻醉管理对癌症生长和扩散的可能影响正受到越来越多的关注。围手术期使用阿片类药物对癌症复发的影响仍存在争议，目前的出版物尚无法进行评估。本研究旨在通过免疫组织化学（IHC）评估接受择期手术的II期和III期结直肠癌患者健康组织和肿瘤组织中阿片受体的差异表达。
倾向评分匹配的病例对照研究嵌套在II期或III期结直肠癌患者的回顾性队列中。主要终点是通过IHC测量的有或无复发受试者肿瘤组织和健康组织中μ-阿片受体（MOR）表达的差异。次要终点是评估匹配样本以及来自癌症基因组图谱（TCGA）和基因型组织表达项目（GTEx）的结直肠癌样本中阿片生长因子受体（OGFR）、环磷酸腺苷（cAMP）产生和蛋白激酶A（PKA）的差异。
肿瘤组织和对照组织中的MOR受体（中位数3 [四分位间距IQR：1 - 3] 和0 [IQR：0 - 2]）和OGFR受体（中位数6 [IQR：5 - 6] 和2 [IQR：1 - 2]）分别存在显著差异（P < 0.001）。然而，两种组织类型之间的cAMP和PKA表达以及按复发状态分析的任何变量的表达均无显著差异。TCGA数据库中的MOR和OGFR表达数据与我们的样本量数据相似，肿瘤样本中MOR表达较低，OGFR表达较高，无论有无复发，肿瘤组织中MOR表达均呈偏态分布。
在II期和III期结直肠癌患者中，MOR和OGFR的总体表达显著增加，但在先前匹配的有或无复发患者之间没有差异。在分析的cAMP - PKA代谢途径中未发现差异：这些结果通过对TCGA - GTEx数据库样本的分析得到证实。
