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CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

Published on Tuesday, 27 June 2023

Abstract

Background: Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1) is a critical metabolic enzyme of melatonin. Although melatonin has been identified to exhibit tumor suppressing activity, the role and mechanism of the clinical and immunological characteristics of CYP1B1 in cancer remain unclear.

Methods: In this study, RNA expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) across 33 solid tumors. The expression, survival, immune subtype, molecular subtype, tumor mutation burden (TMB), microsatellite instability (MSI), biological pathways, and function in vitro and vivo were evaluated. The predictive value of CYP1B1 in immune cohorts was further explored.

Results: We found the dysregulated expression of CYP1B1 was associated with the clinical stage and tumor grade. Immunological correlation analysis showed CYP1B1 was positively correlated with the infiltration of lymphocyte, immunomodulator, chemokine, receptor, and cancer-associated fibroblasts (CAFs) in most cancer. Meanwhile, CYP1B1 was involved in immune subtype and molecular subtype, and was connected with TMB, MSI, neoantigen, the activation of multiple melatonergic and immune-related pathways, and therapeutic resistance.

Conclusions: Together, this study comprehensively revealed the role and mechanism of CYP1B1 and explored the significant association between CYP1B1 expression and immune activity. These findings provide a promising predictor and molecular target for clinical immune treatment.

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- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);