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CN-122012704-A - Application of 5-hydroxymethylcytosine and prognosis model thereof in nasopharyngeal carcinoma prognosis evaluation

CN122012704ACN 122012704 ACN122012704 ACN 122012704ACN-122012704-A

Abstract

The invention relates to the technical field of biology, in particular to 5-hydroxymethylcytosine and application of a prognosis model thereof in nasopharyngeal carcinoma prognosis evaluation. The invention constructs a prognosis scoring model capable of layering patient outcome, which shows strong distinguishing performance in both training set and verification set. When it is integrated into the prognostic model along with tumor stage and EBV status, a 5hmC score yields higher calibration accuracy and net clinical benefit in decision curve analysis. These findings establish that the 5hmC prognostic model, as a noninvasive and biological information-rich marker, can be used for stratification of prognosis risk for NPC patients, and has potential significance for personalized management and improvement of outcome prediction.

Inventors

  • CHEN BIJUAN
  • Zhan Zhouwei
  • XU YUN
  • WANG DI

Assignees

  • 福建省肿瘤医院（福建省肿瘤研究所、福建省癌症防治中心）

Dates

Publication Date
20260512
Application Date
20251219

Claims (10)

  1. Application of 5-hydroxymethyl cytosine in nasopharyngeal carcinoma prognosis evaluation.
  2. 2. The method of claim 1, wherein the prognostic evaluation includes stratification of risk of prognosis of an NPC patient.
  3. 3. The use of claim 2, wherein the risk stratification reflects risks associated with total survival.
  4. Application of a 4.5-hydroxymethylcytosine prognosis model in nasopharyngeal carcinoma prognosis evaluation.
  5. 5. The use of claim 4, wherein the prognostic model includes a 5hmC score.
  6. 6. The use of claim 5, wherein the 5hmC score is obtained by constructing a LASSO-Cox regression model comprising HBQ1, SPATA6L, C QTNF1, CAPN2, FAM72C, HOXA and FTL genes.
  7. 7. The use according to claim 6, wherein the 5hmC score is obtained by multiplying the 5hmC CPM value by its corresponding Cox regression coefficient and summing the multiplied value to obtain the 5hmC score value =FAM72C×0.093 + CAPN2×0.007 + HOXA2×0.1015 + SPATA6L×(−0.0079) + HBQ1×0.2083 + C1QTNF1×0.002 + FTL×0.1422.
  8. 8. The method of claim 5, wherein the prognostic model further comprises a prognostic nomogram, constructed by integrating 5hmC scoring, tumor staging and EBV DNA status.
  9. 9. The method for constructing a prognosis model according to claim 5, comprising the steps of: (1) Constructing a LASO-Cox regression model containing HBQ, SPATA6L, C1QTNF1, CAPN2, FAM72C, HOXA and FTL genes in the training set, establishing a 5hmC score and calculating a 5hmC score value of each patient; (2) The optimal cut-off value for the prognostic score was determined by analysis in the training set using X-Tile software, and patients were classified into high and low groups according to the optimal cut-off value, with high group patient mortality significantly higher than low group, and high group overall survival significantly worse than low group: When the patient's 5hmC score value is greater than the optimal cutoff value, the patient belongs to a high group; When the 5hmC score value of a patient is less than or equal to the optimal cutoff value, the patient belongs to a low group; (3) A prognosis alignment was constructed by integrating the 5hmC score, tumor stage and EBV status and a corresponding calibration map was generated to evaluate the consistency between the predictive probability and the observations.
  10. 10. The method according to claim 9, wherein the optimum cutoff value in step (2) is 1.21.

Description

Application of 5-hydroxymethylcytosine and prognosis model thereof in nasopharyngeal carcinoma prognosis evaluation Technical Field The invention relates to the technical field of biology, in particular to 5-hydroxymethylcytosine and application of a prognosis model thereof in nasopharyngeal carcinoma prognosis evaluation. Background Nasopharyngeal carcinoma (Nasopharyngeal carcinoma, NPC) is an epithelial malignancy originating from the mucosa of the nasopharynx, and occurs mainly in the top and side walls of the nasopharynx, especially in the pharyngeal recess. In terms of symptoms, the early nasopharyngeal carcinoma often does not cause obvious symptoms, and symptoms such as tinnitus, hearing loss, nasal obstruction, nasal discharge with blood, headache and the like, cervical lumps, cranial nerve paralysis and the like can appear in the progressive period. In the aspect of treatment, the nasopharyngeal carcinoma adopts radiation therapy as a main component, and is matched with chemotherapy and targeted therapy. Despite advances in radiotherapy and systemic treatment, a significant proportion of patients, particularly locally advanced patients, experience recurrent or distant metastasis, leading to poor long-term prognosis. The prognosis prediction of nasopharyngeal carcinoma is the judgment of doctor on the condition of nasopharyngeal carcinoma patient, and relates to prediction and evaluation of future development of disease or condition, and making proper quantity of customized therapeutic scheme. Traditional prognostic models based on tumor-lymph node-metastasis (TNM) staging systems provide important risk stratification, but fail to capture biological heterogeneity that affects treatment response and survival. In recent years, various biomarkers including plasma Epstein Barr Virus (EBV) DNA levels, circulating tumor cells, and circulating micrornas have been investigated for prognostic assessment of NPC. Various circulating biomarkers have been studied for risk stratification of NPC, with plasma EBV DNA being the most mature. Although EBV DNA load is related to tumor burden and treatment response, its prognostic performance is dependent on staging and is limited in EBV negative patients. Circulating Tumor Cells (CTCs) and free micrornas have also been explored, but face obstacles to standardization, sensitivity, and clinical transformation. Thus, there is an urgent need for a noninvasive, robust, and biologically informative marker to better predict the outcome of NPC patients and guide personalized treatment. Epigenetic changes based on cfDNA, particularly changes in DNA methylation and hydroxymethyl methylation, play a critical role in cancer occurrence and progression. Among them, 5-hydroxymethylcytosine (5 hmC) has become a key epigenetic modification with unique regulatory functions as a 5-methylcytosine oxidized derivative mediated by the TET enzyme family. Studies have shown that global 5hmC loss is a hallmark of a variety of malignancies, including hematological tumors and solid tumors. Advances in 5hmC-Seal et al technology have enabled sensitive analysis of whole genome 5hmC patterns from circulating free DNA (cfDNA), facilitating the development of noninvasive cancer biomarkers. However, few studies are currently evaluating the prognostic value of circulating 5hmC, and there are no relevant reports of application in the prognosis evaluation of nasopharyngeal carcinoma. Disclosure of Invention The invention aims to solve the technical problem of providing 5-hydroxymethylcytosine and application of a prognosis model thereof in nasopharyngeal carcinoma prognosis evaluation. The invention is realized in the following way: the invention firstly provides application of 5-hydroxymethyl cytosine in nasopharyngeal carcinoma prognosis evaluation. Further, the prognostic evaluation includes stratification of prognostic risk in NPC patients. Still further, the risk stratification reflects risks associated with overall survival. The invention also provides application of the 5-hydroxymethylcytosine prognosis model in nasopharyngeal carcinoma prognosis evaluation. Further, the prognostic model includes a 5hmC score. Still further, the 5hmC score was obtained by constructing a LASSO-Cox regression model containing HBQ1, SPATA6L, C1QTNF1, caps 2, FAM72C, HOXA2, and FTL genes. Specifically, the 5hmC score is obtained by multiplying the 5hmC CPM value by its corresponding Cox regression coefficient and summing the multiplied value to obtain the 5hmC score value =FAM72C×0.093 + CAPN2×0.007 + HOXA2×0.1015 + SPATA6L×(−0.0079) + HBQ1×0.2083 + C1QTNF1×0.002 + FTL×0.1422. Further, the prognostic model also includes a prognostic nomogram, constructed by integrating 5hmC scores, tumor stage, and EBV DNA status. Further, the construction method of the prognosis model comprises the following steps: (1) Constructing a LASO-Cox regression model containing HBQ, SPATA6L, C1QTNF1, CAPN2, FAM72C, HOXA and FTL genes in the