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中华肺部疾病杂志(电子版) ›› 2019, Vol. 12 ›› Issue (05) : 573 -578. doi: 10.3877/cma.j.issn.1674-6902.2019.05.008

论著

EFhd1蛋白在非小细胞肺癌组织中的表达及临床意义
许立芹1, 吕梦源1, 冯健1,()   
  1. 1. 226001 南通,南通大学附属医院呼吸与危重症医学科
  • 收稿日期:2019-04-15 出版日期:2019-10-20
  • 通信作者: 冯健
  • 基金资助:
    南通市新型诊疗技术攻关项目(MS12018038); 南通市应用基础研究关键技术重点研发专项(MS12017005-1); 南通市卫健委青年基金(WQ2016077)

Expression and clinical significance of EFhd1 in patients with non-small cell lung cancer

Liqin Xu1, Mengyuan Lyu1, Jian Feng1,()   

  1. 1. Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
  • Received:2019-04-15 Published:2019-10-20
  • Corresponding author: Jian Feng
引用本文:

许立芹, 吕梦源, 冯健. EFhd1蛋白在非小细胞肺癌组织中的表达及临床意义[J]. 中华肺部疾病杂志(电子版), 2019, 12(05): 573-578.

Liqin Xu, Mengyuan Lyu, Jian Feng. Expression and clinical significance of EFhd1 in patients with non-small cell lung cancer[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2019, 12(05): 573-578.

目的

探讨EFhd1蛋白在非小细胞肺癌(NSCLC)组织中的表达及临床意义。

方法

收集南通大学附属医院心胸外科2004年1月至2011年4月收治的178例NSCLC手术患者的病例及其相应的临床病理和随访资料,并制备组织芯片;采用免疫组化方法检测EFhd1蛋白的表达,统计分析EFhd1蛋白与NSCLC患者临床病理参数、预后之间的相关性。

结果

EFhd1在NSCLC组织(43.3%,77/178)中的表达明显高于癌旁组织(2.0%,1/51),差异有统计学意义(P<0.05)。统计分析显示:EFhd1的表达与T分期有关(P<0.05);Cox单因素分析显示,患者的TNM分期、T分期、N分期与NSCLC的预后密切相关(P<0.01);多因素分析显示EFhd1的高表达以及TNM分期为NSCLC的独立预后因素(P<0.05)。生存曲线提示EFhd1高表达的患者较EFhd1低表达患者生存期短,预后差,TNM分期越晚则生存时间越短。

结论

EFhd1在NSCLC癌组织中的表达较癌旁组织中明显增高;TNM分期和EFhd1蛋白表达程度是影响患者预后的独立危险因素;EFhd1基因的高表达与患者的不良预后密切相关;EFhd1可作为NSCLC诊断及判断预后的潜在分子标记物,为后续研究其作为NSCLC靶向治疗的基因靶点的可能性提供了理论基础。

Objective

To investigate the expression of EFhd1 and its potential value as a prognostic indicator of survival in the patients with primary non-small cell lung cancer (NSCLC).

Methods

A total of 178 NSCLC tissue specimens and 51 paracancerous tissue specimens were collected from 178 NSCLC surgical patients from January 2004 to April 2011 in the Cardiothoracic Surgery Department of the Affiliated Hospital of Nantong University. The clinical data and follow-up data were collected, too. Immunohistochemical analysis with tissue microarray was used to characterize the expression of EFhd1 in the NSCLC tissues. The relationship between the EFhd1 expression and the clinical characteristics and prognosis was determined by statistical analysis.

Results

The level of EFhd1 expression was higher in the NSCLC tissues than in the paracancerous tissues (P<0. 05). The EFhd1 expression in the NSCLC tissues was related to the T staging (P<0.05). Univariate analysis revealed that TNM stage, T stage and N stage were associated with the prognosis of NSCLC (P<0.01). Kaplan Meier survival and Cox regression analyses revealed that the higher level of EFhd1 expression (P=0.037) and later stage grouping by TNM (P=0.001) were independent factors predicting poor prognosis for the patients with NSCLC.

Conclusion

The level of EFhd1 expression in the NSCLC tissues is significantly higher than that in the adjacent tissues. Our finding provides the first evidence that the higher level of EFhd1 expression is associated with the poor prognosis of the patients with NSCLC.

图1 免疫组化方法检测EFhd1在NSCLC组织中的表达;注:A:鳞癌(×40);B:腺癌(×40);C:癌旁组织(×40)
表1 癌组织中EFhd1蛋白表达程度的单因素分析[n(%)]
表2 NSCLC患者预后单因素和多因素分析
图2 生存曲线
1
Pabani A, Butts CA. Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer.[J]. Curr Oncol, 2018, 25(S1): S94-S102.
2
Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90.
3
Osmani L, Askin F, Gabrielson E, et al. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy[J]. Semin Cancer Biol, 2018, 52(Pt 1): 103-109.
4
Khanna P, Blais N, Gaudreau PO, et al. Immunotherapy comes of age in lung cancer[J]. Clin Lung Cancer, 2017, 18: 13-22.
5
Siegel RL, Miller KD, Jemal A. Cancer statistics,2015[J]. CA Cancer J Clin, 2015, 65(1): 5-39.
6
Yang JJ. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma [J]. N Engl J Med, 2009, 361(10): 947-957.
7
Solomon BJ, Mok T, Kim DW, et al. First-Line crizotinib versus chemotherapy in ALK-Positive.lung cancer[J]. N.Engl.J.Med, 2014, 371(23): 2167-2177.
8
Berridge M, Lipp P, Bootman M. Calcium signaling[J]. Curr Biol, 1999, 9(5): R157-159.
9
Haynes WM. CRC handbook of chemistry and physics[J]. CRC press, 2014, 17(6): 342-351.
10
Belgacem YH, Borodinsky LN. Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord[J]. Proc Natl Acad Sci U S A, 2011, 108(11): 4482-4487.
11
Kadio B, Yaya S, Basak A, et al. Calcium role in human carcinogenesis:a comprehensive analysis and critical review of literature[J]. Cancer Metastasis Rev, 2016, 35(3): 391-411.
12
Hajnóczky G, Booth D, Csordás G, et al. Reliance of ER-mitochondrial calcium signaling on mitochondrial EF-hand Ca2+ binding proteins: Miros, MICUs, LETM1 and solute carriers[J]. Curr. Opin. Cell Biol, 2014, 29(5): 133-141.
13
Mootha V.K, Bunkenborg J, Olsen J.V, et al. Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria[J]. Cell, 2003, 11(5): 629-640.
14
Dütting S, Brachs S, Mielenz D. Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions[J]. Cell Commun Signal, 2011, 9(2): 215-231.
15
Lucas B, Grigo K, Erdmann S, et al. HNF4 alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma[J]. Oncogene, 2005, 24(3): 6418-6431.
16
Grigo K, Wirsing A, Lucas B, et al. HNF4 alpha orchestrates a set of 14 genes to down-regulate cell proliferation in kidney cells[J]. Biol Chem, 2008, 389: 179-187.
17
Davidson B, Stavnes HT, Risberg B, et al. Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions[J]. Human Pathology, 2012, 43(7): 684-694.
18
Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma[J]. J Transl Med, 2006, 4(3): 50-63.
19
Hurt EM, Thomas SB, Peng B, et al. Molecular consequences of SOD2 expression in epigenetically silenced pancreatic carcinoma cell lines[J]. Cancer, 2007, 9(7): 1116-1123.
20
Konstantinovsky S, Smith Y, Zilber S. Breast carcinoma cells in primary tumors and effusions have different gene array profiles[J]. J Oncol, 2010, 2(10): 969-984.
21
Takane K, Midorikawa Y, Yagi K, et al. Aberrant promoter methylation of PPP1R3C and EFhd1 in plasma of colorectal cancer patients[J]. Cancer Med, 2014, 3(5): 1235-1245.
22
Urbanczyk S, Stein M, Schuh W, et al. Regulation of Energy Metabolism during Early B Lymphocyte Development[J]. Molecular Sciences, 2018, 22(4): 6418-6431.
23
Stein M, Dütting S, Mougiakakos D, et al. A defined metabolic state in pre B cells governs B-cell development and is counterbalanced by Swiprosin-2/EFhd1[J]. Cell Death Differ, 2017, 24(6): 1239-1252.
24
Bianchi K, Vandecasteele G, Carli C, et al. Regulation of Ca2+ sig-nalling and Ca2+-mediated cell death by the transcriptional coactivator PGC-1α[J]. Cell Death Differ, 2006, 13(4): 586-596.
25
Zhou Z, Zhou J, Du Y. Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects beta-oxidation activity[J]. Mol Cell Proteomics, 2012, 11(7): M111.011056.
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