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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (9): 140-147.doi: 10.6040/j.issn.1671-7554.0.2021.1064

• 科研论著 • 上一篇    下一篇

下咽鳞癌蛋白质谱鉴定及预后靶分子筛选

陈立晓,英信江,陈歆维,王菲,孙臻峰,董频   

  • 发布日期:2021-10-15
  • 通讯作者: 董频. E-mail:dongpin64@aliyun.com
  • 基金资助:
    国家自然科学基金(82072989);上海市申康医院发展中心-新兴前沿技术联合攻关项目(SHDC12020120)

Identification of proteins in hypopharyngeal squamous cell carcinoma by mass spectrometry and screening of prognostic target molecules

CHEN Lixiao, YING Xinjiang, CHEN Xinwei, WANG Fei, SUN Zhenfeng, DONG Pin   

  1. Department of Otorhinolaryngology Head and Neck Surgery, Shanghai General Hospital, Shanghai 200080, China
  • Published:2021-10-15

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摘要： 目的 利用非数据依赖性采集(DIA)蛋白质组学技术筛选下咽鳞癌晚期肿瘤预后相关的特异性靶分子。 方法 选取2016年1月至2018年9月在上海市第一人民医院确诊的5对晚期下咽鳞癌的癌组织和癌旁组织,对蛋白组织进行裂解研磨、蛋白电泳、组织酶解、肽段标记、分级标记、高效液相色谱系统分离,采用Q-Exactive质谱仪完成质谱分析。定量分析及生物信息学分析、筛选预后相关蛋白分子。 结果 建立下咽鳞癌蛋白组学数据库:蛋白质7 395个,肽段63 190个,筛选出的差异蛋白上调36个、下调43个,差异表达蛋白质总数79个。完成层次聚类分析基因本体论和京都基因与基因组百科全书信号通路富集分析、蛋白互做分析,筛选出关键蛋白MRPS5,为下咽鳞癌预后的特异性靶分子。 结论 MRPS5可能为下咽鳞状细胞癌的预后靶分子。

关键词: 下咽鳞癌, 蛋白质组学, 非数据依赖性采集, 预后因子

Abstract: Objective To screen specific target molecules related to the prognosis of advanced hypopharyngeal squamous cell carcinoma using non-data dependent acquisition(DIA)proteomics technology. Methods A total of 5 pairs of advanced hypopharyngeal squamous cell carcinoma and adjacent tissues diagnosed in Shanghai General Hospital during Jan. 2016 and Sep. 2018 were selected. The protein tissues were lysed and ground. Protein electrophoresis, tissue enzymatic hydrolysis, peptide labeling, graded labeling, and high-performance liquid chromatography were performed. Mass spectrometry was performed with Q-Exactive mass spectrometer. Quantitative analysis and bioinformatics analysis were conducted to screen prognosis protein molecules. Quantitative analysis and bioinformatics analysis were used to screen prognosis related protein molecules. Results A proteomics database was established, including 7,395 proteins, 63,190 peptide segments, and 79 differentially expressed proteins(36 up-regulated and 43 down-regulated). After GO and KEGG enrichment, PPI protein network interaction and prognosis analysis, the key protein MPRS5 was selected as the specific target molecule for the prognosis of advanced hypopharyngeal squamous cell carcinoma. Conclusion MRPS5 may become a prognostic target molecule for hypopharyngeal squamous cell carcinoma.

Key words: Hypopharyngeal squamous cell carcinoma, Proteomics, Non-data dependent acquisition, Prognostic factors

中图分类号: 

  • R739.63
[1] Bien S, Kaminski B, Zylka S, et al. The evolution of epidemiology and clinical characteristics of laryngeal and hypopharyngeal carcinoma in Poland from 1991 to 2001 [J]. Otolaryngol Pol, 2005, 59(2): 169-181.
[2] Fakhry C, Psyrri A, Chaturvedhi A. HPV and head and neck cancers: state-of-the-science [J]. Oral Oncol, 2014, 50(5): 353-355.
[3] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 [J]. Int J Cancer, 2015, 136(5): E359-E386.
[4] Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site [J]. Oral Oncol, 2014, 50(5): 387-403.
[5] Byeon HK, Ku M, Yang J. Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer [J]. Exp Mol Med, 2019, 51(1): 1-14.
[6] Gupta S, Kong W, Peng Y, et al. Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States [J]. Int J Cancer, 2009, 125(9): 2159-2165.
[7] 沈枫林, 熊悦婷, 刘晓慧, 等. 基于质谱的蛋白质绝对定量研究策略和建议[J]. 质谱学报, 2021, 42(2): 101-117. SHEN Fenglin, XIONG Yueting, LIU Xiaohui, et al. Strategies and recommendations for the absolute quantification of target proteins based on LC-MS/MS[J]. Journal of Chinese Mass Spectrometry Society, 2021, 42(2): 101-117.
[8] Macmullan MA, Dunn ZS, Graham N, et al. Quantitative proteomics and metabolomics reveal biomarkers of disease as potential immunotherapy targets and indicators of therapeutic efficacy [J]. Theranostics, 2019, 9(25): 7872-7888.
[9] Meyer JG, Schilling B. Clinical applications of quantitative proteomics using targeted and untargeted data-independent acquisition techniques [J]. Expert Rev Proteomics, 2017, 14(5): 419-429.
[10] 陶磊, 周梁, 吴海涛, 等. 154例cN0/cN1下咽鳞状细胞癌颈淋巴清扫效果及预后分析[J]. 中华耳鼻咽喉头颈外科杂志, 2019, 54(4): 272-279. TAO Lei, ZHOU Liang, WU Haitao, et al. Outcome of neck dissection for 154 cN0/cN1 patients with squamous cell carcinoma of hypopharynx and prognostic analysis[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2019, 54(4): 272-279.
[11] Wang LT, Liu KJ, Sytwu HK, et al. Advances in mesenchymal stem cell therapy for immune and inflammatory diseases: use of cell-free products and human pluripotent stem cell-derived mesenchymal stem cells [J]. Stem Cells Transl Med, 2021, 10(9): 1288-1303.
[12] Jiang C, Zhang N, Hu X, et al. Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms [J]. Mol Cancer, 2021, 20(1): 117.
[13] Shui SS, Yao H, Jiang ZD, et al. The differences of muscle proteins between neon flying squid(Ommastrephes bartramii)and jumbo squid(Dosidicus gigas)mantles via physicochemical and proteomic analyses [J]. Food Chem, 2021, 364: 130374. doi: 10.1016/j.foodchem.2021.130374.
[14] Xu W, Anwaier A, Ma C, et al. Multi-omics reveals novel prognostic implication of SRC protein expression in bladder cancer and its correlation with immunotherapy response [J]. Ann Med, 2021, 53(1): 596-610.
[15] Liu J, Zhu W, Li Z, et al. Proteomic analysis of hypop haryngeal and laryngeal squamous cell carcinoma sheds light on differences in survival [J]. Sci Rep, 2020, 10(1): 19459.
[16] Burian A, Lujber L, Gerlinger I, et al. Label-free semiquantitative liquid chromatography-tandem mass spectrometry proteomics analysis of laryngeal/hypopharyngeal squamous cell carcinoma on formalin-fixed, paraffin-embedded tissue samples - a pilot study [J]. Pathol Oncol Res, 2020, 26(4): 2801-2807.
[17] Zhu G, Cai G, Liu Y, et al. Quantitative iTRAQ LC-MS/MS proteomics reveals transcription factor crosstalk and regulatory networks in hypopharyngeal squamous cell carcinoma [J]. J Cancer, 2014, 5(7): 525-536.
[18] Zhou L, Cheng L, Tao L, et al. Detection of hypopharyngeal squamous cell carcinoma using serum proteomics [J]. Acta Otolaryngol, 2006, 126(8): 853-860.
[19] 冉冰冰, 梁楠, 孙辉. 基于质谱的高通量蛋白质组学技术探索肿瘤蛋白标志物的研究进展[J]. 中国肿瘤临床, 2020, 47(8): 411-417. RAN Bingbing,LIANG Nan,SUN Hui. Research progress on tumor protein biomarkers using high throughput proteomics based on mass spectrometry[J]. Chinese Journal of Clinical Oncology, 2020, 47(8): 411-417.
[20] Lee J, Seol M, Jeong S, et al. A Metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma [J]. Medicine, 2015, 94(2): e380. doi:10.1097/MD.0000000000000380.
[21] Akbergenov R, Duscha S, Fritz AK, et al. Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations [J]. EMBO reports,2018, 19(11): e46193. doi:10.15252/embr.201846193.
[22] Wei Z, Jia J, Heng G, et al. Sirtuin‐1/Mitochondrial ribosomal protein S5 axis enhances the metabolic flexibility of liver cancer stem cells [J]. Hepatology, 2019, 70(4): 1197-1213.
[23] Houtkooper RH, Mouchiroud L, Ryu D, et al. Mitonuclear protein imbalance as a conserved longevity mechanism [J]. Nature, 2013, 497(7450): 451-457.
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