广西师范大学学报(自然科学版) ›› 2022, Vol. 40 ›› Issue (6): 196-205.doi: 10.16088/j.issn.1001-6600.2021030702

• 研究论文 • 上一篇    下一篇

一种新型黑色素瘤的蛋白质预后模型

陈雅静1,2,3, 张桐玮1,4, 周俊1,2,3, 陈舒曼1,2,3, 蒲仕明1,2,3*   

  1. 1.广西师范大学生命科学学院, 广西桂林541006;
    2.广西高校干细胞与医药生物技术重点实验室(广西师范大学),广西桂林541004;
    3.广西师范大学生物医学研究中心,广西桂林541004;
    4.广西珍稀濒危动物生态学重点实验室(广西师范大学), 广西桂林541006
  • 收稿日期:2021-03-07 修回日期:2021-06-02 出版日期:2022-11-25 发布日期:2023-01-17
  • 通讯作者: 蒲仕明(1987—),男,四川南充人,广西师范大学助理研究员。E-mail:pushiming77@163.com
  • 基金资助:
    国家自然科学基金(81972700,61827819);广西自然科学基金(2018GXNSFBA281115);广西大学生创新创业训练计划(202010602052)

A Novel Protein Prognostic Model for Melanoma

CHEN Yajing1,2,3, ZHANG Tongwei1,4, ZHOU Jun1,2,3, CHEN Shuman1,2,3, PU Shiming1,2,3*   

  1. 1. College of Life Sciences, Guangxi Normal University, Guilin Guangxi 541006, China;
    2. Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology (Guangxi Normal University), Guilin Guangxi 541004, China;
    3. Research Center for Biomedical Science, Guangxi Normal University, Guilin Guangxi 541004, China;
    4. Guangxi Key Laboratory of Rare and Endangered Animal Ecology (Guangxi Normal University), Guilin Guangxi 541006, China
  • Received:2021-03-07 Revised:2021-06-02 Online:2022-11-25 Published:2023-01-17

摘要: 黑色素瘤是一种最具侵袭性和最难以治疗的癌症之一,目前黑色素瘤的治疗主要是使用靶向药物和免疫治疗药物。然而,受限于耐药性,这些疗法也无法有效改善黑色素瘤患者的预后。因此,需要新的预后方法来指导个体化治疗和改善预后。本文利用TCPA和TCGA数据集的多因素COX分析,建立基于P21、YAP、X1433ZETA、CKIT、S6、CD20、LCK、P27、CD49B、GATA6和SRC_pY416蛋白质的预后模型。风险评分分析显示,风险评分高的患者预后较差。单因素和多因素COX模型分析显示预后与风险评分相关。共表达分析确定了与预后模型中蛋白质共表达的各种蛋白质。将低风险蛋白质GATA6和高风险蛋白质X1433ZETA在黑色素瘤细胞中过表达,GATA6抑制肿瘤生长,X1433ZETA促进肿瘤生长。本文所建立的黑色素瘤预后模型可潜在应用于个体化治疗指导。

关键词: 预后模型, 黑色素瘤, 蛋白质组学, 生物标志物

Abstract: Melanoma is one of the most aggressive and difficult to treat cancers. Currently, Melanoma is mainly treated by using targeted and immunotherapeutic agents. However, their success is limited by the development of resistance, which curtails long-term response rates. Thus, novel prognostic approaches are needed to guide individualized treatment and improve outcomes. In this paper, a multicox analysis of TCPA and TCGA datasets is used to develop a prognostic model based on P21, YAP, X1433ZETA, CKIT, S6, CD20, LCK, P27, CD49B, GATA6 and SRC_pY416 proteins. Risk score analysis for each patient indicated that those with high risk scores had worse prognosis relative to those with low risk scores. Cox and multi-Cox model analyses revealed that prognosis correlated with risk scores. Co-expression analysis identified various proteins that were co-expressed with the prognostic model’s proteins. Overexpression of the low risk protein, GATA6, and the high risk protein X1433ZETA, in melanoma cells revealed tumor growth suppression by GATA6, and tumor growth promotion by X1433ZETA, in vitro and in vivo. In conclusion, this novel melanoma prognostic model can guide individualized treatment.

Key words: prognostic model, melanoma, proteomics, biological marker

中图分类号: 

  • R739.5
[1] JEMAL A, SARAIYA M, PATEL P, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006[J]. Journal of the American Academy of Dermatology, 2011, 65(5): S.e1-S17.e11. DOI: 10.1016/j.jaad.2011.04.032.
[2] GRAY-SCHOPFER V, WELLBROCK C, MARAIS R. Melanoma biology and new targeted therapy[J]. Nature, 2007, 445: 851-857. DOI: 10.1038/nature05661.
[3] DOMINGUES B, LOPES J M, SOARES P, et al. Melanoma treatment in review[J]. ImmunoTargets and Therapy, 2018, 7: 35-49. DOI: 10.2147/ITT.S134842.
[4] Van HALLT, ANDRÉ P, HOROWITZ A, et al. Monalizumab: inhibiting the novel immune checkpoint NKG2A[J]. Journal for Immunotherapy of Cancer, 2019, 7(1): 2633. DOI: 10.1186/s40425-019-0761-3.
[5] 王依凝, 魏文斌. 葡萄膜黑色素瘤的预后评估[J]. 中国医学前沿杂志(电子版), 2020, 12(12): 11-17. DOI: 10.12037/YXQY.2020.12-03.
[6] SOONG S J, DING S L, COIT D, et al. Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database[J]. Annals of Surgical Oncology, 2010, 17(8): 2006-2014. DOI: 10.1245/s10434-010-1050-z.
[7] IPENBURG N A, NIEWEG O E, AHMED T, et al. External validation of a prognostic model to predict survival of patients with sentinel node-negative melanoma[J]. British Journal of Surgery, 2019, 106(10): 1319-1326. DOI: 10.1002/bjs.11262.
[8] BAADE P D, ROYSTON P, YOUL P H, et al. Prognostic survival model for people diagnosed with invasive cutaneous melanoma[J]. BMC Cancer, 2015, 15: 27. DOI: 10.1186/s12885-015-1024-4.
[9] LUO Q Z, ZHANG X B. Construction of protein-related risk score model in bladder. urothelial carcinoma[J]. BioMed Research International, 2020, (2020): 7147824. DOI: 10.1155/2020/7147824.
[10] WU Z H, YUN-TANG, CHENG Q. Data mining identifies six proteins that can act as prognostic markers for head and neck squamous cell carcinoma[J]. Cell Transplantation, 2020, 29: 1-8. DOI: 10.1177/0963689720929308.
[11] RONG D W, DONG Q, QU H J, et al. m6A-induced LINC00958 promotes breast cancer tumorigenesis via themiR-378a-3p/YY1 axis[J].Cell Death Discovery, 2021, 7(1): 27. DOI: 10.1038/s41420-020-00382-z.
[12] ZHU P P, HE F, HOU Y X, et al. A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability[J]. Oncogene, 2021, 40(9): 1609-1627. DOI: 10.1038/s41388-020-01638-9.
[13] FRIEDMAN E B, SHANG S L, de MIERA E V S, et al. Serum microRNAs as biomarkers for recurrence in melanoma[J]. Journal of Translational Medicine, 2012, 10: 155. DOI: 10.1186/1479-5876-10-155.
[14] FANG X S, LIU X, WENG C Y, et al. Construction and validation of a protein prognostic model for lung squamous cell carcinoma[J]. International Journal of Medical Sciences, 2019, 17(17): 2718-2727. DOI: 10.7150/ijms.47224.
[15] TIAN X, XU W H, ANWAIER A, et al. Construction of a robust prognostic model for adult adrenocortical carcinoma: results from bioinformatics and real-world data[J]. Journal of Celluar and Molecular Medicine, 2021, 25(8): 3898-3911. DOI: 10.1111/jcmm.16323.
[16] 韩未, 沈国良. CDCA5在皮肤恶性黑色素瘤中的表达及其与预后相关性的生物信息学分析[J], 现代肿瘤医学, 2021, 29(7): 1234-1240. DOI: 10.3969/j.issn.1672-4992.2021.07.028.
[17] KOLLMAR O, RUPERTUS K, SCHEUER C, et al. Stromal cell-derived factor-1 promotes cell migration, tumor growth of colorectal metastasis[J]. Neoplasia, 2007, 9(10): 862-870. DOI: 10.1593/neo.07559.
[18] RUSSELL M R, GRAHAM C, D'AMATO A, et al. Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel[J]. British Journal of Cancer, 2019, 121(6): 483-489. DOI: 10.1038/s41416-019-0544-0.
[19] LI W, GAO L N, SONG P P, et al. Development and validation of a RNA binding protein-associated prognostic model for lung adenocarcinoma[J]. Aging, 2020, 12(4): 3558-3573. DOI: 10.18632/aging.102828.
[20] XU W H, ANWAIER A, MA C G, et al. Multi-omics reveals novel prognostic implication of SRC protein expression in bladder cancer and its correlation with immunotherapy response[J]. Annals of Medicine, 2021, 53(1): 596-610. DOI: 10.1080/07853890.2021.1908588.
[21] ZENG Q Z, YAO Y O, ZHAO M W. Development and validation of a nomogram to predict cancer-specific survival of uveal melanoma[J]. BMC Ophthalmology, 2021, 21(1): 230. DOI: 10.1186/s12886-021-01968-6.
[22] ZHANG M G, GAO F, YU X, et al. LINC00261: a burgeoning long noncoding RNA related to cancer[J]. Cancer Cell International, 2021, 21(1): 274. DOI: 10.1186/s12935-021-01988-8.
[23] HAN P H, ZHU J J, FENG G, et al. Characterization of alternative splicing events and prognostic signatures in breast cancer[J]. BMC Cancer, 2021, 21(1): 587. DOI: 10.1186/s12885-021-08305-6.
[24] ABBASPOUR B M, KAMALIDEHGHAN B, SALEEM M, et al. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells[J]. Drug Design, Development and Therapy, 2016, 10: 2443-2459. DOI: 10.2147/DDDT.S89114.
[25] KANG H G, MA D, ZHANG J, et al. Long non-coding RNA GATA6-AS1 upregulates GATA6 to regulate the biological behaviors of lung adenocarcinoma cells[J]. BMC Pulmonary Medicine, 2021, 21(1): 166. DOI: 10.1186/s12890-021-01521-7.
[26] HU D, ANSARI D, PAWŁOWSKI K, et al. Proteomic analyses identify prognostic biomarkers for pancreatic ductal adenocarcinoma[J]. Oncotarget, 2018, 9(11): 9789-9807. DOI: 10.18632/oncotarget.23929.
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