A novel miRNA-based signature as predictive tool of survival outcome of colorectal cancer patients

被引:5
作者
Zhao, Bochao [1 ]
Wang, Weiqiang [1 ]
Ye, Haikun [1 ]
Wang, Jingchao [1 ]
Meng, Kewei [1 ]
Yang, Tao [1 ]
机构
[1] Tianjin First Cent Hosp, Dept Gastrointestinal Surg, Tianjin, Peoples R China
关键词
colorectal cancer; miRNAs; prognostic; signature; survival prediction; MICRORNA SIGNATURES; TARGET; METASTASIS; CARCINOMA; PROLIFERATION; MIR-193A-3P; ONCOGENE; PACKAGE;
D O I
10.1111/cbdd.14301
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It is great significance of identifying valuable biomarkers for early diagnosis and prognostic prediction of colorectal cancer (CRC) patients. This study aimed at developing and validating a miRNAs-based signature as prognostic tool for CRC patients. The miRNA expression profile of 624 CRC samples (613 tumor tissues and 11 normal tissues) was analyzed, and 523 differentially expressed miRNAs (DEmiRNAs) were identified, in which 191 were downregulated and 332 were upregulated. All patients were randomly divided into a training cohort (N = 308) and an internal validation cohort (N = 200). Using the least absolute shrinkage and selection operator (LASSO) and Cox regression model, a prognostic signature of 10 miRNAs (hsa-miR-149-5p, hsa-miR-193b-5p, hsa-miR-193a-3p, hsa-miR-3677-3p, hsa-miR-29a-3p, hsa-miR-200c-5p, hsa-miR-200a-5p, hsa-miR-6854-5p, hsa-miR-216a-5p and hsa-miR-891a-5p) was developed in the training cohort. The risk score was calculated by the product of the expression level and the coefficients of each miRNA. The prognostic value of 10 miRNAs-based signature for CRC patients was tested and validated. Survival analysis indicated that high-risk patients (> 1.10) had a worse overall survival (OS) than low-risk (= 1.10) patients (5-year OS rate for training cohort: 59.3% vs. 78.9%, p < .001; validation cohort: 48.3% vs. 69.3%, p = .011). The miRNA-based signature was an independent prognostic factor for CRC patients (HR for training cohort:2.476, 95% CI:1.202-5.098, p = .014; HR for validation cohort:2.050, 95% CI:1.087-3.869, p = .027). The AUC values for 3-year and 5-year OS prediction were 0.718 and 0.784 in the training cohort, 0.659 and 0.614 in the validation cohort, respectively. The 10 miRNAs-based signature provided a proper prognostic stratification for CRC patients, and it might be a promising tool for survival prediction.
引用
收藏
页码:1024 / 1033
页数:10
相关论文
共 39 条
  • [1] Predicting effective microRNA target sites in mammalian mRNAs
    Agarwal, Vikram
    Bell, George W.
    Nam, Jin-Wu
    Bartel, David P.
    [J]. ELIFE, 2015, 4
  • [2] cAMP Signaling in Cancer: A PKA-CREB and EPAC-Centric Approach
    Ahmed, Muhammad Bilal
    Alghamdi, Abdullah A. A.
    Ul Islam, Salman
    Lee, Joon-Seok
    Lee, Young-Sup
    [J]. CELLS, 2022, 11 (13)
  • [3] MicroRNAs: Target Recognition and Regulatory Functions
    Bartel, David P.
    [J]. CELL, 2009, 136 (02) : 215 - 233
  • [4] MicroRNA signatures in human cancers
    Calin, George A.
    Croce, Carlo M.
    [J]. NATURE REVIEWS CANCER, 2006, 6 (11) : 857 - 866
  • [5] Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression
    Chen, Pengju
    Yao, Yunfeng
    Yang, Nan
    Gong, Lifei
    Kong, Yuanyuan
    Wu, Aiwen
    [J]. CELL DEATH & DISEASE, 2020, 11 (07)
  • [6] miRDB: an online database for prediction of functional microRNA targets
    Chen, Yuhao
    Wang, Xiaowei
    [J]. NUCLEIC ACIDS RESEARCH, 2020, 48 (D1) : D127 - D131
  • [7] MicroRNAs in Cancer
    Lee, Yong Sun
    Dutta, Anindya
    [J]. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2009, 4 : 199 - 227
  • [8] MicroRNAs as important contributors in the pathogenesis of colorectal cancer
    Ghafouri-Fard, Soudeh
    Hussen, Bashdar Mahmud
    Badrlou, Elham
    Abak, Atefe
    Taheri, Mohammad
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2021, 140
  • [9] Guo F, 2016, AM J CANCER RES, V6, P2463
  • [10] MicroRNAs in cancer: biomarkers, functions and therapy
    Hayes, Josie
    Peruzzi, Pier Paolo
    Lawler, Sean
    [J]. TRENDS IN MOLECULAR MEDICINE, 2014, 20 (08) : 460 - 469