Home page News Related Researches 2020-2029

Identifying potential mechanisms of circadian rhythm-related gene marker prognosis, immune infiltration, and melatonin intervention in thyroid cancer based on bioinformatics and network pharmacology

Published on Friday, 28 November 2025

Abstract

Thyroid cancer (THCA) patients may be affected by circadian rhythm disorder (CRD). Since melatonin (MT) has both antitumor and regulatory effects on CRD, this study aimed to evaluate the functional role and potential mechanism of action of MT as a therapeutic agent against THCA and regulation of CRD.

The intersection between differentially expressed genes of THCA and circadian rhythm-related genes (CRGs) was identified and hub genes were further screened to construct a prognostic model. The relationship between the expression of THCA/CRGs and immune infiltration was evaluated in the low-risk and high-risk groups. The molecular targets of MT acting on THCA/CRGs were screened and topological analysis was performed.

Multivariate Cox regression analysis identified 3 core genes, COL18A1, DPP4, and APOE, to construct the prognostic model. The clinical information analysis and immunohistochemical analysis of core genes showed that in THCA, COL18A1 was downregulated (P < .05), while DPP4 and APOE were upregulated (P < .05).

Subgroup analysis showed that COL18A1, DPP4, and APOE may be associated with different factors in different subgroups. The results of immune infiltration analysis showed that compared with the low-risk group, the high-risk group had higher stromal score (P < .001), lower immune score (P < .001), and ESTIMATE score (P < .001).

Additionally, the expression of THCA/CRGs was closely associated with the infiltration of various immune cells. A total of 25 molecular targets of MT against THCA/CRD were identified by online databases. Topological analysis identified 6 molecular targets with the best performance, including LGALS3, MMP9, CTSB, DPP4, PPARG, and ALB, with binding energy <-5 kcal/mol for molecular docking with MT.

The prediction model constructed in this study shows good diagnostic and prognostic performance. In addition, this study revealed the pharmacological targets of MT against THCA/CRD, providing a potential theoretical basis for exploring new clinical treatment options.

Download the complete article

About this publication.

The Di Bella's Method: Use Melatonin (together with others chemical compounds) in Head and Neck Cancer:

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day and more 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 - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Variable Part - Selenium methonine, 40 μg capsules, twice a day);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

The Di Bella's Method: Use of Melatonin since 1974 - together with others chemical compounds - in several Oncological Pathologies:

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;