The measurement of NRF2 and TP53 in blood expects radiotherapeutic sensitivity in patients with esophageal cancer

Huiqin Xu; Jinchang Wu; Lansheng Zhang; Yang Li; Liyan Gao; Yufeng Cheng

doi:10.1016/j.mcp.2022.101860

The measurement of NRF2 and TP53 in blood expects radiotherapeutic sensitivity in patients with esophageal cancer

Mol Cell Probes. 2022 Dec:66:101860. doi: 10.1016/j.mcp.2022.101860. Epub 2022 Sep 16.

Authors

Huiqin Xu¹, Jinchang Wu², Lansheng Zhang², Yang Li², Liyan Gao³, Yufeng Cheng⁴

Affiliations

¹ Radiotherapy Center, Qilu hospital of Shandong University, Jinan city, Shandong Province, 25000, China; Radiotherapy Department, The Second Affiliated Hospital of Xuzhou Medical University (Xuzhou Mining Group General Hospital), Xuzhou City, Jiangsu Province, 221000, China. Electronic address: 13585397309@139.com.
² Radiotherapy Department, The Second Affiliated Hospital of Xuzhou Medical University (Xuzhou Mining Group General Hospital), Xuzhou City, Jiangsu Province, 221000, China.
³ Xuzhou Medical University, Xuzhou City, Jiangsu Province, 221000, China.
⁴ Radiotherapy Center, Qilu hospital of Shandong University, Jinan city, Shandong Province, 25000, China. Electronic address: qlcyf@163.com.

PMID: 36116599
DOI: 10.1016/j.mcp.2022.101860

Abstract

Objective: This study investigates the relationship between the mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and Tumor protein p53 (TP53) in circulating tumor cells (CTC) and sensitivity to radiotherapy in patients with esophageal cancer. To investigate the relationship between cytokines IL-6, CD8⁺, and NRF2 during patient treatment and their predictive role for treatment.

Methods: Radiosensitivity was assessed by measuring a morphological or functional change in the tumor in response to ionizing radiation. Fasting venous anticoagulated blood (EDTA anticoagulation) was drawn from patients, and the Trizol-chloroform two-step method was used for RNA extraction. Data were collected from 45 patients admitted with radiotherapy alone from January 2018 to December 2021. The expression levels of NRF2mRNA (Messenger Ribose Nucleic Acid) and TP53mRNA in CTCs were detected by reverse transcription-polymerase chain reaction (RT-PCR). Pre- and post-treatment changes in IL-6 and CD8⁺ were recorded. The correlation between their expression level and the clinical stage, radiotherapy sensitivity, and efficacy of patients was analyzed.

Results: Twenty-six cases were sensitive to radiotherapy, and 19 were resistant, for a radiotherapy sensitivity rate of 58.8%. NRF2mRNA and TP53mRNA values increased in 19 radiotherapy-resistant patients and decreased in 26 radiotherapy-sensitive patients compared with those before radiotherapy (P = 0.001, P＜0.05). The ΔCT values of NRF2mRNA and TP53mRNA before treatment were moderately correlated with prognosis (P < 0.002). Inflammatory cytokine IL-6 was elevated in 22 of 45 patients after radiation, P = 0.04. NRF2 mRNA level was consistently elevated with CD8⁺ in 10 patients, P = 0.02.

Conclusions: The expression of NRF2mRNA and TP53mRNA in the CTCs found in the peripheral blood of patients with esophageal squamous carcinoma was significantly associated with the sensitivity to radiotherapy. NRF2 mRNA level was consistently elevated with CD8⁺ and IL-6 in patients.

Keywords: Esophageal cancer; NRF2; RT-PCR; Radiation sensitivity; Radiation therapy; TP53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Esophageal Neoplasms* / genetics
Esophageal Neoplasms* / pathology
Esophageal Neoplasms* / radiotherapy
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism
NF-E2-Related Factor 2* / genetics
NF-E2-Related Factor 2* / metabolism
RNA, Messenger / genetics
Tumor Suppressor Protein p53 / genetics

Substances

NF-E2-Related Factor 2
Tumor Suppressor Protein p53
Interleukin-6
RNA, Messenger
TP53 protein, human