Increased mu-opioid receptor expression is associated with reduced disease-free and overall survival in laryngeal squamous cell carcinoma

Zhang, Hao; Sun, Meiyan; Zhou, Di; Görür, Ayşegül; Sun, Zhirong; Zeng, Weian; Cata, Juan P.; Chen, Wankun; Miao, Changhong

doi:10.1016/j.bja.2020.07.051

Cited by 32 publications

(33 citation statements)

References 24 publications

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“…Further research on the function of MOR showed upregulated MOR expression in the tumor tissues from patients with prostate cancer and that high MOR expression was positively correlated with the metastasis of prostate cancer [ 13 ]. Similar results were obtained from studies of esophageal and laryngeal squamous cell carcinoma [ 14 , 15 ]. Singleton et al analyzed the clinical specimens from 34 patients with lung cancer and found twofold higher MOR expression in lung cancer tissue than that in adjacent normal lung tissue [ 16 ].…”

Section: Introductionsupporting

confidence: 87%

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

Liu

Yang

et al. 2021

Cancer Cell Int

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Background Morphine, a µ-opioid receptor (MOR) agonist, has been shown to be related to the activity of cancer cells, and a higher morphine dosage reduces the survival time of patients with lung cancer. However, the effect of morphine on the malignant behavior of lung cancer cells remains unclear. The aim of this study was to investigate the specific molecular mechanism by which morphine regulates the malignant biological behavior of non-small cell lung cancer. Methods Immunofluorescence staining and Western blot analyses were performed to detect MOR expression. H460 non-small cell lung cancer cells were used in this study, and cell proliferation, the cell cycle and apoptosis were evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Cell migration and invasion were detected using wound healing and Transwell assays. The effect of morphine on lung cancer development in vivo was examined by performing a xenograft tumor assay following morphine treatment. Results Morphine promoted the growth of H460 cells both in vivo and in vitro. Morphine enhanced cell migration and invasion, modified cell cycle progression through the S/G2 transition and exerted an antiapoptotic effect on H460 cells. Additionally, morphine increased Rous sarcoma oncogene cellular homolog (Src) phosphorylation and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Treatment with the MOR antagonist methylnaltrexone (MNTX) and the Src inhibitor protein phosphatase 1 (PP1) reduced the phosphorylation induced by morphine. Furthermore, MNTX, PP1, and the PI3K/AKT inhibitor deguelin reversed the antiapoptotic effect of morphine on lung cancer cells. Conclusion Morphine promotes the malignant biological behavior of H460 cells by activating the MOR and Src/mTOR signaling pathways.

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Section: Introductionsupporting

confidence: 87%

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

Liu

Yang

et al. 2021

Cancer Cell Int

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“…In a cohort of 239 patients with esophageal squamous cell carcinoma, the expression of MOR did not affect survival (14). Contrarily, other studies demonstrated that high levels of MOR expression were a marker of worse prognosis in patients with laryngeal and lung cancers (8,15). and long-term survival in cancer patients.…”

Section: Discussionmentioning

confidence: 93%

“…PDAC tissue fixed on paraffin blocks were obtained for immunohistochemistry (IHC). IHC staining was performed as previously described (8). Briefly, the anti-Mu Opioid Receptor (UMB3)-C-terminal (ab134054) antibody was used in a concentration of 1:200.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Secondary antibodies anti-Goat Anti-Rabbit IgG H&L (HRP) (ab205718) were used. Two investigators (physician pathologists) blinded to the data were asked to assessed and scored MOR expression based on previously published criteria (8). The total MOR score was calculated based on staining intensity and proportion of immun0possitive in cancer cells (10).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Over the past few years, there has been increasing interest to elucidate whether MOR or its encoding gene OPRM1 can be used as predictive biomarkers in different cancers (5). Studies indicate that a high expression of MOR in malignant specimens were associated with worse survival outcome in patients with lung cancer, hepatocellular carcinoma, and laryngeal squamous cell carcinoma (6)(7)(8). However, other studies have found that high levels of expression of MOR were not associated with poor prognosis in colorectal and oesophageal squamous cell carcinomas (9,10).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Görür

et al. 2021

Front. Oncol.

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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.

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The µ‐Opioid Receptor in Cancer and Its Role in Perineural Invasion: A Short Review and New Evidence

et al. 2022

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Increased mu-opioid receptor expression is associated with reduced disease-free and overall survival in laryngeal squamous cell carcinoma

Cited by 32 publications

References 24 publications

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

Morphine promotes the malignant biological behavior of non-small cell lung cancer cells through the MOR/Src/mTOR pathway

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

The µ‐Opioid Receptor in Cancer and Its Role in Perineural Invasion: A Short Review and New Evidence

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