Association of Mu-Opioid Receptor(MOR) Expression and Opioids Requirement With Survival in Patients With Stage I-III Pancreatic Ductal Adenocarcinoma

Abstract

BackgroundThe use of opioids in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is associated with shorter survival and not dependent on the expression of the mu-opioid receptor (MOR). The role of opioid use and MOR expression in stage I-III PDAC has not been investigated.MethodsWe conducted retrospective study in patients with stage I-III PDAC. MOR expression and OPRM1 gene expression in tumour tissue and non-tumour tissue was measured. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints included perineural invasion, intraoperative sufentanil consumption, and length of stay. We performed a subgroup group analysis to evaluate the interaction between levels of MOR expression, amount of opioids use (high versus low) and its association with survival.ResultsA total of 236 patients were enrolled in this study.There were no significantly difference in OS rates in patients with high versus low levels of MOR (1-year OS: 65.2% versus 70.6%, P=0.064; 3-year: 31.4% versus 35.8%, P=0.071; 5-year: 19.4% versus. 16.2%, P=0.153, respectively) in the tumours. The DFS rates between the groups were no significantly difference. Of note, a high expression of MOR combined with high opioid consumption was associated with poor prognosis in stage I-III PDAC patients. Tumor expressing high levels of MOR show higher rates of perineural invasion.ConclusionMOR is not an independent predictor of poor survival in stage I-III PDAC but associated with perineural invasion. Patients requiring high amounts of opioids intraoperatively show worse outcome if they are expressing high levels of MOR.

Association of Mu-Opioid Receptor Expression With Long-Term Survival and Perineural Nerve Invasion in Patients Undergoing Surgery for Ovarian Cancer

“…Briefly, the intensity of MOR was graded from 0 to 3, and the percentage of MOR positive was also graded from 0 to 3 (score 0: <25% positive, score 1: 25%–50% positive, score 2: 51%–75% positive, and score 3: >75% positive). A total score from 0 to 6 was calculated ( 11 ). PNI was defined as cancer cells that invade the perineural spaces of surrounding nerves ( 17 ).…”

“…Previous clinical studies have found that a high tumoral MOR expression is associated with poor prognosis in hepatocellular, laryngeal, and lung cancers ( 8 – 10 ). Furthermore, MOR expression was associated with high perineural nerve invasion (PNI), a clinical predictor of survival in pancreatic and laryngeal cancers ( 9 , 11 ). In contrast, other studies have found that MOR expression is not a predictor of worse long-term survival in pancreatic and colorectal cancers ( 11 – 13 ).…”

“…Furthermore, MOR expression was associated with high perineural nerve invasion (PNI), a clinical predictor of survival in pancreatic and laryngeal cancers ( 9 , 11 ). In contrast, other studies have found that MOR expression is not a predictor of worse long-term survival in pancreatic and colorectal cancers ( 11 – 13 ).…”

Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

“…Changes in expression of μ, δ, or κ-opioid receptors in cancer cells or tissues are reported in various cancer types and overall, point to an increased expression in cancer. The majority of studies described an increase in μOR ( 18 – 22 ), while some reports showed no significant differences in μOR expression levels between the tumour and adjacent non-tumour tissues ( 23 , 24 ). No studies reported a decreased expression of OR in cancer.…”

Could the perioperative use of opioids influence cancer outcomes after surgery? A scoping review protocol

“…To date, however, most of the scientific evidence in favour of this thesis comes from preclinical studies6 while clinical data have been mainly extrapolated from retrospective analyses 7 8. For example, since preclinical investigations demonstrated that the mu-opioid receptor (MOR) is often expressed in cancer tissues, patients requiring increased intraoperative opioid doses could show worse outcomes, especially if they express high MOR levels 9. Interestingly, the expression of MORs in some tumours (eg, pancreatic ductal adenocarcinoma) and not in others could explain how, in some studies, the higher intraoperative opioid administration could be associated with better oncological outcomes 7.…”