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CN-121995055-A - Method for improving sensitivity of esophageal squamous carcinoma patient to novel auxiliary radiotherapy and chemotherapy

CN121995055ACN 121995055 ACN121995055 ACN 121995055ACN-121995055-A

Abstract

The invention provides a method for improving sensitivity of esophageal squamous carcinoma (ESCC) patients to novel auxiliary radiotherapy and chemotherapy. Specifically, the invention improves the sensitivity of ESCC patients to novel auxiliary radiotherapy and chemotherapy by reducing the levels of CEBPB, AREG and/or EREG proteins, inhibiting mitochondrial oxidative phosphorylation (OXPHOS), inhibiting TCA cycle, and/or inhibiting ERBB signaling pathway. In addition, the invention also provides a method for predicting the sensitivity of ESCC patients to the novel auxiliary radiotherapy and chemotherapy and a biomarker for predicting the sensitivity of ESCC patients.

Inventors

  • MA XIUMEI
  • HAO YUJUN
  • LIN ZHANG
  • Yao Meilian
  • XU XIN
  • CUI GAOPING
  • ZHANG DONG
  • YE QING

Assignees

  • 上海交通大学医学院附属仁济医院

Dates

Publication Date
20260508
Application Date
20250813

Claims (10)

  1. 1. A method of predicting susceptibility of esophageal squamous carcinoma (ESCC) patients to neoadjuvant radiotherapy, the method comprising: A. providing a sample to be tested of an ESCC patient; B. detecting the AREG and/or EREG protein content in the sample to be detected to obtain a detection value C1 of the AREG content and a detection value C2 of the EREG, and C. Comparing C1 and C2 with cutoff values of AREG and/or EREG proteins, thereby judging whether the ESCC patient is sensitive to new auxiliary chemoradiotherapy or not; wherein the AREG protein has a serum cutoff value of 103.6pg/ml, The serum cutoff value of the EREG protein was 150.1pg/ml.
  2. 2. The method of claim 1, wherein the sample to be tested is selected from a serum sample, a cancer tissue sample, or a combination thereof.
  3. 3. The method of claim 1, wherein the patient is determined to be insensitive to neoadjuvant chemotherapy if C1>103.6pg/ml and/or C2>150.1pg/ml, and wherein the patient is determined to be sensitive to neoadjuvant chemotherapy if C1<103.6pg/ml and/or C2<150.1 pg/ml.
  4. 4. The method of claim 1, wherein the cutoff values for the AREG and/or EREG proteins further comprise a tissue immunohistochemical score of 10.5 points for both AREG and EREG proteins.
  5. 5. The method of claim 4, wherein the patient is determined to be insensitive to neoadjuvant chemotherapy if the AREG and/or EREG protein tissue immunohistochemical score of the test sample is greater than 10.5 points, and wherein the patient is determined to be sensitive to neoadjuvant chemotherapy if the AREG and/or EREG protein tissue immunohistochemical score of the test sample is less than 10.5 points.
  6. 6. A method of increasing sensitivity of an esophageal squamous carcinoma (ESCC) patient to neoadjuvant radiotherapy (nCRT), the method comprising: 1) Lowering the level of CEBPB, AREG and/or EREG proteins; 2) Inhibit mitochondrial oxidative phosphorylation (OXPHOS) and/or TCA cycle, and/or 3) Inhibit ERBB signal paths. In another preferred embodiment, the modulating the level of AREG and/or EREG protein.
  7. 7. The method of claim 6, wherein the level of CEBPB, AREG and/or EREG protein is positively correlated with nCRT resistance.
  8. 8. The method of claim 6, wherein the OXPHOS activity is positively correlated with nCRT resistance.
  9. 9. The method of claim 6, wherein inhibiting the ERBB pathway reduces OXPHOS activity, thereby increasing sensitivity of the ESCC patient to nCRT.
  10. 10. A highly sensitive ESCC cell line for neoadjuvant radiotherapy and chemotherapy, characterized in that said ESCC cell line is an ESCC cell line treated with the method of claim 2.

Description

Method for improving sensitivity of esophageal squamous carcinoma patient to novel auxiliary radiotherapy and chemotherapy Technical Field The invention belongs to the field of biological medicine, and in particular relates to a method for improving sensitivity of esophageal squamous carcinoma patients to novel auxiliary radiotherapy and chemotherapy. Background Esophageal Cancer (EC) is the ninth most common malignancy worldwide and is also the sixth leading cause of cancer-related death. In east asia, 80% of cases of esophageal cancer are Esophageal Squamous Cell Carcinoma (ESCC). For ESCC in the local advanced stage, a post-neoadjuvant radiotherapy (nCRT) surgery is the standard treatment regimen. However, the efficacy of nCRT on ESCC varies from person to person. About 30-50% of nCRT patients are able to achieve complete pathological remission (pCR) and achieve long-term survival, but a significant number of patients also experience short-term recurrence or disease progression. Recent studies indicate that those patients who achieved clinically complete remission but refused surgery are similar in overall survival to those who received standard surgical resection following nCRT, suggesting that nCRT may be a viable method of organ preservation in these patients. In view of the key role of radiation therapy (IR) in improving nCRT efficacy, researchers have placed increasing emphasis on revealing molecular mechanisms and predictive biomarkers of ESCC patient radiation sensitivity. Metabolic reprogramming is a significant feature of cancer, which causes Esophageal Squamous Cell Carcinoma (ESCC) cells to develop radiation resistance through adaptive plasticity. The glycolytic pathway is particularly important in responding to radiation therapy. The upregulation of glycolytic enzymes (e.g., GLUT1, HK2, PDK 1) by radiotherapy enhances glycolytic capacity and radioresistance (metabolism plays a role in cancer cell radioresistance and radiosensitization methods) of ESCC cells. Thus, as a primary substrate for glycolysis, accumulation of lactic acid is associated with radioresistance. High expression of the TCA cycle enzyme IDH2 (isocitrate dehydrogenase 2) confers EC radiation resistance. Furthermore, several metabolites have been identified as biomarkers for predicting nCRT responses, however, there is inconsistency in the prediction of metabolites as biomarkers in different studies, and thus the key metabolic mechanism of esophageal squamous cell carcinoma radiation resistance is still unclear. The metabolic pathway of the radiation response is often regulated by oncogenic signaling pathways. However, it is not clear how oncogenic signals in ESCC regulate metabolism to increase radiation resistance. Disclosure of Invention The invention aims to provide a marker for predicting sensitivity of esophageal squamous carcinoma to novel auxiliary chemoradiotherapy. In a first aspect of the invention, there is provided a method of predicting susceptibility of an Esophageal Squamous Cell Carcinoma (ESCC) patient to neoadjuvant chemotherapy, the method comprising: A. providing a sample to be tested of an ESCC patient; B. detecting the AREG and/or EREG protein content in the sample to be detected to obtain a detection value C1 of the AREG content and a detection value C2 of the EREG, and C. Comparing C1 and C2 with cutoff values of AREG and/or EREG proteins, thereby judging whether the ESCC patient is sensitive to new auxiliary chemoradiotherapy or not; wherein the AREG protein has a serum cutoff value of 103.6pg/ml, The serum cutoff value of the EREG protein was 150.1pg/ml. In another preferred embodiment, the sample to be tested is selected from a serum sample, a cancer tissue sample, or a combination thereof. In another preferred embodiment, if C1>103.6pg/ml and/or C2>150.1pg/ml, the patient is determined to be insensitive to neoadjuvant chemotherapy. In another preferred embodiment, if C1<103.6pg/ml and/or C2<150.1pg/ml, the patient is determined to be susceptible to neoadjuvant chemotherapy. In another preferred embodiment, the cutoff value of the AREG and/or EREG protein further comprises a cutoff value of a tissue immunohistochemical score. In another preferred embodiment, the archg and EREG proteins have a histoimmunohistochemical score of 10.5 points for each. In another preferred embodiment, if the AREG and/or EREG protein tissue immunohistochemical score of the sample to be tested is greater than 10.5 points, the patient is judged to be insensitive to neoadjuvant radiotherapy and chemotherapy. In another preferred embodiment, if the AREG and/or EREG protein tissue immunohistochemical score of the sample to be tested is less than 10.5 points, the patient is judged to be sensitive to the novel adjuvant radiotherapy and chemotherapy. In a second aspect of the invention, there is provided a method of increasing sensitivity of an esophageal squamous carcinoma (ESCC) patient to neoadjuvant radiotherapy (nCRT), the m