切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2021, Vol. 14 ›› Issue (04) : 412 -416. doi: 10.3877/cma.j.issn.1674-6902.2021.04.002

论著

NIX蛋白表达与非小细胞肺癌临床病理特征及预后
陈燏1, 王玉秀2, 闵凌峰2,()   
  1. 1. 214500 靖江,江苏省靖江人民医院
    2. 225001 扬州,江苏省苏北人民医院·大连医科大学第二临床学院·扬州大学临床医学院
  • 收稿日期:2021-01-08 出版日期:2021-08-25
  • 通信作者: 闵凌峰
  • 基金资助:
    国家自然科学基金资助项目(81870033); 江苏省"六大人才高峰计划"(2015-WSN-106); 江苏省医学科学研究基金(QNRC2016340); 扬州市"十三五"高层次人才科研基金(ZDRC201866)

Nip-like protein Xis overexpressed and predicts poor prognosis in non-small cell lung cancer

Yu Chen1, Yuxiu Wang2, Lingfeng Min2,()   

  1. 1. Department of Respiratory Medicine, Jingjiang People′s Hospital, Yangzhou University, Jingjiang 214500, China
    2. Department of Respiratory of Subei People′s Hospital, The Second Clinical Medical College of Dalian Medical University, Clinical Medical College of Yangzhou University, Yangzhou, 225001, China
  • Received:2021-01-08 Published:2021-08-25
  • Corresponding author: Lingfeng Min
引用本文:

陈燏, 王玉秀, 闵凌峰. NIX蛋白表达与非小细胞肺癌临床病理特征及预后[J/OL]. 中华肺部疾病杂志(电子版), 2021, 14(04): 412-416.

Yu Chen, Yuxiu Wang, Lingfeng Min. Nip-like protein Xis overexpressed and predicts poor prognosis in non-small cell lung cancer[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2021, 14(04): 412-416.

目的

探讨Nip样蛋白(Nip-like protein X,NIX/BNIP3L)在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达情况及其临床特征和预后中的影响。

方法

选择在江苏省靖江市人民医院就诊首次确诊为NSCLC并行手术治疗的68例患者的癌组织、癌旁组织及其临床特征信息,用免疫组化法检测癌组织以及癌旁组织NIX表达情况,分析NIX表达情况与患者临床病理特征之间的相关性及对其预后的影响。

结果

免疫组化结果显示NIX在NSCLC组织表达较癌旁组织明显上调,并且NIX表达差异与NSCLC患者分化程度、淋巴结转移程度存在明显的相关性(P=0.001,P=0.005),而与患者性别、年龄、病理类型、远处转移、TNM分期无明显的相关性。多因素Cox回归分析显示NIX蛋白表达、区域淋巴结转移、病理分化程度、吸烟状况可作为非小细胞肺癌患者的独立预后因子。基于NIX在NACLC表达差异,K-M分析结果显示NIX表达的上调与患者总体生存率以及无进展生存率的下降存在明显的相关性(P<0.01)。

结论

NIX在NSCLC中的表达明显上调,NIX的表达上调可能与NSCLC的侵袭转移存在一定的相关性,NIX的表达上调可影响NSCKLC患者的预后,NIX有望成为NSCLC的治疗一新靶点。

Objective

To investigate the expression and clinical significance of Nip-like protein X (NIX/BNIP3L) in non-small cell lung cancer (NSCLC).

Methods

It was collected that tumor and adjacent tissue samples from 68 patients with NSCLC, and conducted immunohistochemistry to detect NIX expression. The correlations between NIX expression and clinicopathologic characteristics and prognosis were evaluated using the SPSS 22.0 software package.

Results

NIX was highly expressed in NSCLC tissue samples. NIX expression was correlated with the degree of NSCLC differentiation and lymph node metastasis(P=0.001, P=0.005), but not with sex, age, pathologic type, distant metastasis, or TNM stage. In addition, multivariate Cox regression analysis showed that NIX protein expression, regional lymph node metastasis, pathological differentiation, and smoking status were independent prognostic factors for NSCLC patients.Based on the differences of NIX expression in NACLC, TheK-M analysis results showed that the upregulation of NIX expression was significantly correlated with the decrease of overall survival rate and progression-free survival rateinNSCLC(P<0.01).

Conclusion

NIX expression is elevated in NSCLC and may contribute to the invasion and metastasis of lung cancer. Upregulation of NIX expression can affect the prognosis of NSCLC patients.NIX may represent a therapeutic target for the treatment of NSCLC.

图1 NSCLC癌组织中NIX的表达情况;注:NIX在肺癌组织中的表达位于细胞质;左侧标本为NIX低表达,右侧标本为NIX高表达;上方为100×镜下显示结果,下方为400×镜下显示结果
表1 NSCLC患者组织中NIX的表达与患者临床病理特征的关系
表2 临床指标Cox回归分析
图2 K-M分析;注:NSCLC组织中NIX表达与NSCLC患者的疾病总生存期(OS)/无进展期(PFS)相关;NIX低表达者OS/PFS优于高表达者(P<0.01)
1
钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2
Boutet M, Gauthier L, Leclerc M, et al. TGFbeta signaling intersects with CD103 integrin signaling to promote T-Lymphocyte accumulation and antitumor activity in the lung tumor microenvironment[J]. Cancer Res, 2016, 76(7): 1757-1769.
3
Ko JC, Chen JC, Wang TJ, et al. Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells[J]. Biochem Pharmacol, 2016, 105: 91-100.
4
Schweers RL, Zhang J, Randall MS, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation[J]. Proc Natl Acad Sci USA, 2007, 104(49): 19500-19505.
5
Schwarten M, Mohrluder J, Ma P, et al. Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy[J]. Autophagy, 2009, 5(5): 690-698.
6
Panigrahi DP, Praharaj PP, Bhol CS, et al. The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics[J]. Semin Cancer Biol, 2020, 66: 45-58.
7
Sowter HM, Ferguson M, Pym C, et al. Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade[J]. J Pathol, 2003, 201(4): 573-580.
8
Mellor HR, Harris AL. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer[J]. Cancer Metastasis Rev, 2007, 26(3-4): 553-566.
9
Xiang Z, Mo Z, Li G, et al. 125I brachytherapy in the palliation of painful bone metastases from lung cancer after failure or rejection of conventional treatments[J]. Oncotarget, 2016, 7(14): 18384-18393.
10
Feng L, Tong R, Liu X, et al. A network-based method for identifying prognostic gene modules in lung squamous carcinoma[J]. Oncotarget, 2016, 7(14): 18006-18020.
11
Sherwood JL, Corcoran C, Brown H, et al. Optimised pre-analytical methods improve KRAS mutation detection in circulating tumour DNA (ctDNA) from patients with non-small cell lung cancer (NSCLC)[J]. PLoS One, 2016, 11(2): e150197.
12
Jung J, Zhang Y, Celiku O, et al. Mitochondrial NIX promotes tumor survival in the hypoxic niche of glioblastoma[J]. Cancer Res, 2019, 79(20): 5218-5232.
13
Humpton TJ, Alagesan B, Denicola GM, et al. Oncogenic KRAS Induces NIX-mediated mitophagy to promote pancreatic cancer[J]. Cancer Discov, 2019, 9(9): 1268-1287.
14
Hrustanovic G, Bivona TG. RAS signaling in ALK fusion lung cancer[J]. Small GTPases, 2016, 7(1): 32-33.
15
付 洁,吴 斌. 阿法替尼在EGFR突变的晚期非小细胞肺癌患者治疗中的预算影响分析[J]. 中国现代应用药学,2019, 36(6): 723-725.
16
Palikaras K, Lionaki E, Tavernarakis N. Mitophagy: In sickness and in health[J]. Mol Cell Oncol, 2016, 3(1): e1056332.
17
Liu X, Lu X, Zhen F, et al. LINC00665 induces acquired resistance to gefitinib through recruiting EZH2 and activating PI3K/AKT pathway in NSCLC[J]. Mol Ther Nucleic Acids, 2019, 16: 155-161.
18
Dong Q, Yu P, Ye L, et al. PCC0208027, a novel tyrosine kinase inhibitor, inhibits tumor growth of NSCLC by targeting EGFR and HER2 aberrations[J]. Sci Rep, 2019, 9(1): 5692.
19
Wang J, Zhou P, Wang X, et al. Rab25 promotes erlotinib resistance by activating the beta1 integrin/AKT/beta-catenin pathway in NSCLC[J]. Cell Prolif, 2019: e12592.
20
Zhang Z, Zhang M, Liu H, et al. AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells[J]. J Cell Biochem, 2019, 120(1): 756-767.
21
Li W, Chen H, Li S, et al. Exploring microRNAs on NIX-dependent mitophagy[J]. Methods Mol Biol, 2018, 1759: 111-121.
22
Rogov VV, Suzuki H, Marinkovic M, et al. Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins[J]. Sci Rep, 2017, 7(1): 1131.
23
Yamano S, Gi M, Tago Y, et al. Role of deltaNp63(pos)CD44v(pos) cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas[J]. Cancer Sci, 2016, 107(2): 123-132.
24
Taverna S, Giallombardo M, Gil-Bazo I, et al. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice[J]. Oncotarget, 2016, 7(19): 28748-28760.
25
Chen CY, Jan CI, Pi WC, et al. Heterogeneous nuclear ribonucleoproteins A1 and A2 modulate expression of Tid1 isoforms and EGFR signaling in non-small cell lung cancer[J]. Oncotarget, 2016, 7(13): 16760-16772.
26
Sano H, Futamura M, Gaowa S, et al. p53/Mieap-regulated mitochondrial quality control plays an important role as a tumor suppressor in gastric and esophageal cancers[J]. Biochem Biophys Res Commun, 2020, 529(3): 582-589.
27
Claude-Taupin A, Fonderflick L, Gauthier T, et al. ATG9A is overexpressed in triple negative breast cancer and its in vitro extinction leads to the inhibition of pro-cancer phenotypes[J]. Cells, 2018, 7(12): 248.
28
Madhu V, Boneski PK, Silagi E, et al. Hypoxic regulation of mitochondrial metabolism and mitophagy in nucleus pulposus cells is dependent on HIF-1alpha-BNIP3 axis[J]. J Bone Miner Res, 2020, 35(8): 1504-1524.
29
Aerbajinai W, Giattina M, Lee YT, et al. The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation[J]. Blood, 2003, 102(2): 712-717.
30
Lu Y, Wang L, He M, et al. Nix protein positively regulates NF-kappa B activation in gliomas[J]. PLoS One, 2012, 7(9): e44559.
31
Sowter HM, Ferguson M, Pym C, et al. Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade[J]. J Pathol, 2003, 201(4): 573-580.
32
Brennan LA, Mcgreal-Estrada R, Logan CM, et al. BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation[J]. Exp Eye Res, 2018, 174: 173-184.
[1] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[2] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[3] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[4] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[5] 梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[6] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[7] 李伟, 宋子健, 赖衍成, 周睿, 吴涵, 邓龙昕, 陈锐. 人工智能应用于前列腺癌患者预后预测的研究现状及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 541-546.
[8] 关小玲, 周文营, 陈洪平. PTAAR在乙肝相关慢加急性肝衰竭患者短期预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 841-845.
[9] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[10] 刘郁, 段绍斌, 丁志翔, 史志涛. miR-34a-5p 在结肠癌患者的表达及其与临床特征及预后的相关性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 485-490.
[11] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[12] 曾明芬, 王艳. 急性胰腺炎合并脂肪肝患者CT 与彩色多普勒超声诊断参数与其病情和预后的关联性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 531-535.
[13] 沈炎, 张俊峰, 唐春芳. 预后营养指数结合血清降钙素原、胱抑素C及视黄醇结合蛋白对急性胰腺炎并发急性肾损伤的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 536-540.
[14] 王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
[15] 郭曌蓉, 王歆光, 刘毅强, 何英剑, 王立泽, 杨飏, 汪星, 曹威, 谷重山, 范铁, 李金锋, 范照青. 不同亚型乳腺叶状肿瘤的临床病理特征及预后危险因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(06): 524-532.
阅读次数
全文


摘要