High Expression of TIMM17B Is a Potential Diagnostic and Prognostic Marker of Breast

被引:0
作者
Duan, Mingting [1 ]
Ren, Yun [2 ]
Zhang, Jiwen [1 ]
Zhang, Tingting [3 ]
Wang, Yanhong [4 ]
Jia, Hongyan [5 ]
机构
[1] Shanxi Med Univ, Dept Clin Med 1, Taiyuan, Peoples R China
[2] Shanxi Med Univ, Dept Breast Surg, Changzhi Peoples Hosp, Changzhi, Peoples R China
[3] Shanxi Med Univ, Basic Med Sci Ctr, Sch Basic Med, Taiyuan, Peoples R China
[4] Shanxi Med Univ, Dept Microbiol & Immunol, Taiyuan, Peoples R China
[5] Shanxi Med Univ, Dept Breast Surg, Hosp 1, Taiyuan, Peoples R China
关键词
Malignant tumor; cell cycle; TIMM17B; GPX4; CANCER STATISTICS; IMMUNOTHERAPY; MITOCHONDRIA; TRANSLOCASE; INTERACTS; PROTEINS;
D O I
10.14715/cmb/2023.69.3.25
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
Breast cancer (BC) is the most common malignant tumor in women. TIMM17B has been found to be related to the cell cycle. The purpose of this study was to explore the diagnostic and prognostic value of TIMM17B in BC and its correlation with tumor immune infiltration and ferroptosis. For this purpose, the transcription and expression profile of TIMM17B between BC and normal tissues was downloaded from The Cancer Genome Atlas (TCGA). To verify the expression of TIMM17B in BC, we analyzed it by immunohistochemical stai-ning. The correlation between TIMM17B and clinical features was analyzed using the R package to establish a ROC diagnostic curve. The GSVA package was used to determine the relationship between TIMM17B gene expression levels and immune infiltration. The GDSC was used to predict the IC50 of the drug. Expression of TIMM17B in tamoxifen-resistant breast cancer cells was detected by protein immunoblot analysis. Results showed that the expression of TIMM17B in many kinds of malignant tumors was higher than that in para-cancer, with a significantly high expression in BC (P < 0.001). We validated this result by analyzing tissue microarrays. ROC curve analysis showed an AUC value in TIMM17B of 0.920. The Kaplan-Meier method showed a better prognosis for patients with high expression of TIMM17B in basal BC than that of patients with low expression of TIMM17B (HR=2.32 (1.09-4.94), P=0.038). In addition, the expression of TIMM17B in BC was negatively correlated with the level of immune infiltration, Tcm cells, T helper cells, and immune targets such as CD274, HAVCR2, and PDCD1LG2. At the same time, the expression of TIMM17B in BC was significantly correlated with the drug resistance and the expression of GPX4 and other key enzymes of ferroptosis. Protein immunoblot analysis revealed high expression of TIMM17B in tamoxifen-resistant breast cancer cells. In conclusion, the expression of TIMM17B in BC was significantly increased, and it was related to immune infiltration, drug resistance and ferroptosis in BC. Our research shows that TIMM17B can be used as a diagnostic index of BC and one of the targets of immunotherapy.
引用
收藏
页码:169 / 176
页数:8
相关论文
共 30 条
  • [1] X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
    Asselta, Rosanna
    Paraboschi, Elvezia M.
    Gerussi, Alessio
    Cordell, Heather J.
    Mells, George F.
    Sandford, Richard N.
    Jones, David E.
    Nakamura, Minoru
    Ueno, Kazuko
    Hitomi, Yuki
    Kawashima, Minae
    Nishida, Nao
    Tokunaga, Katsushi
    Nagasaki, Masao
    Tanaka, Atsushi
    Tang, Ruqi
    Li, Zhiqiang
    Shi, Yongyong
    Liu, Xiangdong
    Xiong, Ma
    Hirschfield, Gideon
    Siminovitch, Katherine A.
    Carbone, Marco
    Cardamone, Giulia
    Duga, Stefano
    Gershwin, M. Eric
    Seldin, Michael F.
    Invernizzi, Pietro
    [J]. GASTROENTEROLOGY, 2021, 160 (07) : 2483 - +
  • [2] Triple-negative breast cancer therapeutic resistance: Where is the Achilles' heel?
    Bai, Xupeng
    Ni, Jie
    Beretov, Julia
    Graham, Peter
    Li, Yong
    [J]. CANCER LETTERS, 2021, 497 : 100 - 111
  • [3] Ferroptosis in Hepatocellular Carcinoma: Mechanisms, Drug Targets and Approaches to Clinical Translation
    Bekric, Dino
    Ocker, Matthias
    Mayr, Christian
    Stintzing, Sebastian
    Ritter, Markus
    Kiesslich, Tobias
    Neureiter, Daniel
    [J]. CANCERS, 2022, 14 (07)
  • [4] Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020
    Cao, Wei
    Chen, Hong-Da
    Yu, Yi-Wen
    Li, Ni
    Chen, Wan-Qing
    [J]. CHINESE MEDICAL JOURNAL, 2021, 134 (07) : 783 - 791
  • [5] Mitochondrial presequence translocase: Switching between TOM tethering and motor recruitment involves Tim21 and Tim17
    Chacinska, A
    Lind, M
    Frazier, AE
    Dudek, J
    Meisinger, C
    Geissler, A
    Sickmann, A
    Meyer, HE
    Truscott, KN
    Guiard, B
    Pfanner, N
    Rehling, P
    [J]. CELL, 2005, 120 (06) : 817 - 829
  • [6] Importing Mitochondrial Proteins: Machineries and Mechanisms
    Chacinska, Agnieszka
    Koehler, Carla M.
    Milenkovic, Dusanka
    Lithgow, Trevor
    Pfanner, Nikolaus
    [J]. CELL, 2009, 138 (04) : 628 - 644
  • [7] Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
    Dixon, Scott J.
    Lemberg, Kathryn M.
    Lamprecht, Michael R.
    Skouta, Rachid
    Zaitsev, Eleina M.
    Gleason, Caroline E.
    Patel, Darpan N.
    Bauer, Andras J.
    Cantley, Alexandra M.
    Yang, Wan Seok
    Morrison, Barclay, III
    Stockwell, Brent R.
    [J]. CELL, 2012, 149 (05) : 1060 - 1072
  • [8] Breast Cancer Immunotherapy: Facts and Hopes
    Emens, Leisha A.
    [J]. CLINICAL CANCER RESEARCH, 2018, 24 (03) : 511 - 520
  • [9] CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer
    Esteva, Francisco J.
    Wang, Jing
    Lin, Feng
    Mejia, Jaime A.
    Yan, Kai
    Altundag, Kadri
    Valero, Vicente
    Buzdar, Aman U.
    Hortobagyi, Gabriel N.
    Symmans, W. Fraser
    Pusztai, Lajos
    [J]. BREAST CANCER RESEARCH, 2007, 9 (06)
  • [10] Immunotherapy and targeted therapy combinations in metastatic breast cancer
    Esteva, Francisco J.
    Hubbard-Lucey, Vanessa M.
    Tang, Jun
    Pusztai, Lajos
    [J]. LANCET ONCOLOGY, 2019, 20 (03) : E175 - E186