Construction and validation of a ubiquitination-related prognostic risk score signature in breast cancer
Kexin Feng,
Xin He,
Ling Qin,
Zihuan Ma,
Siyao Liu,
Ziqi Jia,
Fei Ren,
Heng Cao,
Jiang Wu,
Dongxu Ma,
Xiang Wang,
Zeyu Xing
Affiliations
Kexin Feng
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Xin He
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Ling Qin
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Zihuan Ma
Beijing ChosenMed Clinical Laboratory Co. Ltd., Jinghai Industrial Park, Economic and Technological Development Area, Beijing, 100176, China
Siyao Liu
Beijing ChosenMed Clinical Laboratory Co. Ltd., Jinghai Industrial Park, Economic and Technological Development Area, Beijing, 100176, China
Ziqi Jia
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Fei Ren
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Heng Cao
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Jiang Wu
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Dongxu Ma
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
Xiang Wang
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; Corresponding author.
Zeyu Xing
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; Corresponding author.
Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p < 0.01 were screened again using the Non-negative Matrix Factorization (NMF) algorithm, and the resulting hub genes were composed of a risk score signature. Patients were categorized into two risk groups, and the predictive effect was tested using Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves. This risk score signature was later validated using multiple external datasets, namely TCGA-BRAC, GSE1456, GSE16446, GSE20711, GSE58812 and GSE96058. Immuno-microenvironmental, single-cell, and microbial analyses were also performed. Results: The selected gene signature comprising six ubiquitination-related genes (ATG5, FBXL20, DTX4, BIRC3, TRIM45, and WDR78) showed good prognostic power in patients with BC. It was validated using multiple externally validated datasets, with KM curves showing significant differences in survival (p < 0.05). The KM curves also demonstrated superior predictive ability compared to traditional clinical indicators. Single-cell analysis revealed that Vd2 gd T cells were less abundantin the low-risk group, whereas patients in the high-risk group lacked myeloid dendritic cells. Tumor microbiological analysis revealed a notable variation in microorganism diversity between the high- and low-risk groups. Conclusion: This study established an risk score signature consisting of six ubiquitination genes, that can accurately forecast the outcome of patients with BC using multiple datasets. It can provide personalized and targeted assistance to provide the evaluation and therapy of individuals having BC.
