Novel role of the Mu-opioid receptor in pancreatic cancer: potential link between opioid use and cancer progression

Haque, Muhammad R.; Barlass, Usman; Armstrong, Andrew; Shaikh, Maliha; Bishehsari, Faraz

doi:10.1007/s11010-022-04377-5

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…The expressions of classical opioid receptors were predominantly low in tumor tissues. This appears to be in contrast with the findings of several previous studies on the OPRM1 gene [34][35][36] known to regulate tumor development and immune response, but there are reasons for this inconsistency. The OPRM1 gene expression is dependent on immune cell activation, as OPRM1 expression in T cells is non-constitutive, and this may account for the discrepancy.…”

Section: Discussioncontrasting

confidence: 97%

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Wu,

Chen,

Huang

et al. 2023

IJGM

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Introduction The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies. Methods This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes. Results OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR’s impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma. Conclusion In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker.

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Section: Discussioncontrasting

confidence: 97%

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Wu,

Chen,

Huang

et al. 2023

IJGM

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“…In the same study examining the role of the mu-opioid receptor (MOR) in cancer progression and recurrence, increased MOR expression was observed in PC organoids and undifferentiated regions of resected PC tissue, suggesting its involvement in cancer progression. 197 Meanwhile, the pathogenesis of CCA associated with primary sclerosing cholangitis (PSC) remains largely unknown. Hence, CCA organoids were exposed to five cytokines (IL-1β, IL-6, IL-17A, interferon-γ, and TNF-α) and the effects on cell proliferation were assessed; only IL-17A had a proliferative effect on cells.…”

Section: Application Of Digestive Tract Tumor Organoidsmentioning

confidence: 99%

Revolutionizing digestive system tumor organoids research: Exploring the potential of tumor organoids

Xiu,

Yang,

Xie

et al. 2024

J Tissue Eng

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Digestive system tumors are the leading cause of cancer-related deaths worldwide. Despite ongoing research, our understanding of their mechanisms and treatment remain inadequate. One promising tool for clinical applications is the use of gastrointestinal tract tumor organoids, which serve as an important in vitro model. Tumor organoids exhibit a genotype similar to the patient’s tumor and effectively mimic various biological processes, including tissue renewal, stem cell, and ecological niche functions, and tissue response to drugs, mutations, or injury. As such, they are valuable for drug screening, developing novel drugs, assessing patient outcomes, and supporting immunotherapy. In addition, innovative materials and techniques can be used to optimize tumor organoid culture systems. Several applications of digestive system tumor organoids have been described and have shown promising results in related aspects. In this review, we discuss the current progress, limitations, and prospects of this model for digestive system tumors.

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“…Colorectal cancer cells express MORs, suggesting a role in disease progression [ 19 , 41 ]. Even aggressive pancreatic cancer expresses the MOR gene [ 42 , 43 ]. MOR in pancreatic cancer cells modulates neurotransmitter production, which may affect tumor–environment nervous and immune system interactions.…”

Section: Mor Biology In Cancermentioning

confidence: 99%

Opioids and Cancer: Current Understanding and Clinical Considerations

Sah,

Shoffel-Havakuk,

Tsur

et al. 2024

Current Oncology

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Pain is one of the most common symptoms in patients with cancer. Pain not only negatively affects the quality of life of patients with cancer, but it has also been associated with reduced survival. Pain management is therefore a critical component of cancer care. Prescription opioids remain the first-line approach for the management of moderate-to-severe pain associated with cancer. However, there has been increasing interest in understanding whether these analgesics could impact cancer progression. Furthermore, epidemiological data link a possible association between prescription opioid usage and cancer development. Until more robust evidence is available, patients with cancer with moderate-to-severe pain may receive opioids to decrease suffering. However, future studies should be conducted to evaluate the role of opioids and opioid receptors in specific cancers.

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Novel role of the Mu-opioid receptor in pancreatic cancer: potential link between opioid use and cancer progression

Cited by 10 publications

References 26 publications

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4

Revolutionizing digestive system tumor organoids research: Exploring the potential of tumor organoids

Opioids and Cancer: Current Understanding and Clinical Considerations

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