

浏览全部资源
扫码关注微信
复旦大学附属肿瘤医院检验科,复旦大学上海医学院肿瘤学系,上海 200032
LU Renquan.
Received:28 September 2022,
Revised:2022-11-02,
Published:30 January 2023
移动端阅览
Chunyuan ZOU, Xiaofeng XU, Renquan LU, et al. Detection of p53, PGP9.5, SOX2, GAGE7, GBU4-5 and MAGE A1 protein levels in lung cancer tissues and peripheral blood and their clinical value[J]. China Oncology, 2023, 33(1): 36-44.
Chunyuan ZOU, Xiaofeng XU, Renquan LU, et al. Detection of p53, PGP9.5, SOX2, GAGE7, GBU4-5 and MAGE A1 protein levels in lung cancer tissues and peripheral blood and their clinical value[J]. China Oncology, 2023, 33(1): 36-44. DOI: 10.19401/j.cnki.1007-3639.2023.01.004.
背景与目的:
肺癌发病机制具有多样性,但一经确认,往往已错过最佳治疗时机,本文通过探讨肺癌组织和外周血中抑癌基因(p53)、蛋白基因产物(PGP9.5)、转录因子(SOX2)、肿瘤相关基因编码蛋白(GAGE7)、解旋酶(GBU4-5)和黑色素瘤抗原(MAGE A1)蛋白水平的相关性,同时分析其在肺癌诊疗中的应用价值。
方法:
回顾并分析2018年5月—2020年5月在复旦大学附属肿瘤医院确诊的100例肺癌患者的病历资料,临床TNM分期Ⅰ期25例,Ⅱ期45例,Ⅲa期30例;非小细胞肺癌80例,小细胞肺癌20例;取手术切除的肿瘤组织和癌旁组织,采用免疫组织化学染色法检测上述6种蛋白的水平,采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain re
action,RTFQ-PCR)法检测其基因表达,采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测外周血中6种蛋白的抗体阳性情况。
结果:
肿瘤组织中p53、PGP9.5、SOX2、GAGE7、GBU4-5和MAGE A1蛋白的阳性率和基因表达水平均明显高于癌旁组织(
P
<
0.05);将其与肿瘤的临床病理学特征进行相关分析发现,肿瘤组织和外周血中的p53、PGP9.5、SOX2、GAGE7、GBU4-5和MAGE A1蛋白的阳性率和基因表达水平与肿瘤TNM分期和分化级别有关(
P
<
0.05),而与患者性别、年龄、肿瘤直径、病理学类型无关(
P
>
0.05)。肿瘤组织中6种蛋白的表达水平与外周血清表达具有较好的一致性(
P
>
0.05)。
结论:
肺癌肿瘤组织和外周血中p53、PGP9.5、SOX2、GAGE7、GBU4-5和MAGE A1蛋白表达阳性与肿瘤TNM分期及分化级别密切相关。
Background and purpose:
The pathogenesis of lung cancer is diverse
however once confirmed
the best time for treatment is often missed. In this paper
the correlation between tumor suppressor gene (p53)
protein gene product (PGP9.5)
transcription factor (SOX2)
tumor-associated gene protein (GAGE7)
helicase (GBU4-5) and melanoma antigen (MAGE A1) protein levels in lung cancer tissues and peripheral blood of patients was discussed
and its application value in the diagnosis and treatment of lung cancer was analyzed.
Methods:
A total of 100 lung cancer patients in Fudan University Shanghai Cancer Center from May 2018 to May 2019 were enrolled
including 25 cases of clinical TNM stage Ⅰ
45 cases of stage Ⅱ
30 cases of stage Ⅲa
80 cases of non-small cell lung cancer and 20 cases of small cell lung cancer. Following surgical removal of intact tumor tissues and cancer-adjacent tissues
immunohistochemical staining was used to detect positive rates of above-mentioned 6 proteins
real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect their gene expression levels
and enzyme-linked immunosorbent assay (ELISA) was performed to detect antibody positive rates in peripheral serum.
Results:
The positive rates and gene expression levels of p53
PGP9.5
SOX2
GAGE7
GBU4-5 and MAGE A1 in tumor tissues were significantly higher compared with adjac
ent tissues (
P
<
0.05). Correlation analysis between p53
PGP9.5
SOX2
GAGE7
GBU4-5 and MAGE A1 proteins in tumor tissues and serum showed that the positive rates and gene expression levels of P53
PGP9.5
SOX2
GAGE7
GBU4-5 and MAGE A1 were correlated with TNM stage and differentiation level (
P
<
0.05). There was no significant difference in gender
age
tumor diameter and pathological type (
P
>
0.05). The protein expression levels of p53
PGP9.5
SOX2
GAGE7
GBU4-5 and MAGE A1 in tumor tissues were consistent with their expression levels in peripheral blood (
P
>
0.05).
Conclusion:
Positive expressions of p53
PGP9.5
SOX2
GAGE7
GBU4-5 and MAGE A1 protein in lung cancer tissues and peripheral serum were closely related to TNM staging and differentiation.
BADE B C , DELA CRUZ C S . Lung cancer 2020: epidemiology, etiology, and prevention [J ] . Clin Chest Med , 2020 , 41 ( 1 ): 1 - 24 . DOI: S0272-5231(19)30080-2 http://doi.org/S0272-5231(19)30080-2
ZHOU Y Y , HÖTI N , AO M H , et al . Expression of p16 and p53 in non-small cell lung cancer: clinicopathological correlation and potential prognostic impact [J ] . Biomark Med , 2019 , 13 ( 9 ): 761 - 771 . DOI: 10.2217/bmm-2018-0441 http://doi.org/10.2217/bmm-2018-0441 https://www.futuremedicine.com/doi/10.2217/bmm-2018-0441 https://www.futuremedicine.com/doi/10.2217/bmm-2018-0441
BRAIT M , MALDONADO L , NOORDHUIS M G , et al . Association of promoter methylation of VGF and PGP9.5 with ovarian cancer progression [J ] . PLoS One , 2013 , 8 ( 9 ): e70878 . DOI: 10.1371/journal.pone.0070878 http://doi.org/10.1371/journal.pone.0070878 https://dx.plos.org/10.1371/journal.pone.0070878 https://dx.plos.org/10.1371/journal.pone.0070878
WANG K X , JI W X , YU Y F , et al . FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer [J ] . Oncogene , 2018 , 37 ( 39 ): 5340 - 5354 . DOI: 10.1038/s41388-018-0311-3 http://doi.org/10.1038/s41388-018-0311-3
WANG J , SHIVAKUMAR S , BARKER K , et al . Comparative study of autoantibody responses between lung adenocarcinoma and benign pulmonary nodules [J ] . J Thorac Oncol , 2016 , 11 ( 3 ): 334 - 345 . DOI: 10.1016/j.jtho.2015.11.011 http://doi.org/10.1016/j.jtho.2015.11.011
ORLOVETSKIE N , SERRUYA R , ABBOUD-JARROUS G , et al . Targeted inhibition of WRN helicase, replication stress and cancer [J ] . Biochim Biophys Acta Rev Cancer , 2017 , 1867 ( 1 ): 42 - 48 . DOI: 10.1016/j.bbcan.2016.11.004 http://doi.org/10.1016/j.bbcan.2016.11.004 https://linkinghub.elsevier.com/retrieve/pii/S0304419X16301111 https://linkinghub.elsevier.com/retrieve/pii/S0304419X16301111
YI E , CHANG J E , LEEM C , et al . Association of MAGE A1-6 expression with lung cancer progression [J ] . J Cancer , 2017 , 8 ( 8 ): 1324 - 1329 . DOI: 10.7150/jca.18086 http://doi.org/10.7150/jca.18086
ZHANG X Z , LIU M , ZHANG X , et al . Autoantibodies to tumor-associated antigens in lung cancer diagnosis [J ] . Adv Clin Chem , 2021 , 103 : 1 - 45 . DOI: 10.1016/bs.acc.2020.08.005 http://doi.org/10.1016/bs.acc.2020.08.005
XIAO K J , MA X L , WANG Y C , et al . Diagnostic value of serum tumor-associated autoantibodies in esophageal cancer [J ] . Biomark Med , 2021 , 15 ( 15 ): 1333 - 1343 . DOI: 10.2217/bmm-2021-0351 http://doi.org/10.2217/bmm-2021-0351
ZHANG R , MA L , LI W Y , et al . Diagnostic value of multiple tumor-associated autoantibodies in lung cancer [J ] . Onco Targets Ther , 2019 , 12 : 457 - 469 . DOI: 10.2147/OTT.S187734 http://doi.org/10.2147/OTT.S187734 https://www.dovepress.com/diagnostic-value-of-multiple-tumor-associated-autoantibodies-in-lung-c-peer-reviewed-article-OTT https://www.dovepress.com/diagnostic-value-of-multiple-tumor-associated-autoantibodies-in-lung-c-peer-reviewed-article-OTT
DU Q , YU R F , WANG H , et al . Significance of tumor-associated autoantibodies in the early diagnosis of lung cancer [J ] . Clin Respir J , 2018 , 12 ( 6 ): 2020 - 2028 . DOI: 10.1111/crj.12769 http://doi.org/10.1111/crj.12769
CHAPMAN C J , HEALEY G F , MURRAY A , et al . EarlyCDT ® -Lung test: improved clinical utility through additional autoantibody assays [J ] . Tumour Biol , 2012 , 33 ( 5 ): 1319 - 1326 . DOI: 10.1007/s13277-012-0379-2 http://doi.org/10.1007/s13277-012-0379-2 http://link.springer.com/10.1007/s13277-012-0379-2 http://link.springer.com/10.1007/s13277-012-0379-2
CHAPMAN C J , MURRAY A , MCELVEEN J E , et al . Autoantibodies in lung cancer: possibilities for early detection and subsequent cure [J ] . Thorax , 2008 , 63 ( 3 ): 228 - 233 . DOI: 10.1136/thx.2007.083592 http://doi.org/10.1136/thx.2007.083592
INFANTE M , CAVUTO S , LUTMAN F R , et al . A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial [J ] . Am J Respir Crit Care Med , 2009 , 180 ( 5 ): 445 - 453 . DOI: 10.1164/rccm.200901-0076OC http://doi.org/10.1164/rccm.200901-0076OC https://www.atsjournals.org/doi/10.1164/rccm.200901-0076OC https://www.atsjournals.org/doi/10.1164/rccm.200901-0076OC
PARRALES A , IWAKUMA T . Targeting oncogenic mutant p53 for cancer therapy [J ] . Front Oncol , 2015 , 5 : 288 . DOI: 10.3389/fonc.2015.00288 http://doi.org/10.3389/fonc.2015.00288
QIN J Y , ZENG N , YANG T , et al . Diagnostic value of autoantibodies in lung cancer: a systematic review and meta-analysis [J ] . Cell Physiol Biochem , 2018 , 51 ( 6 ): 2631 - 2646 . DOI: 10.1159/000495935 http://doi.org/10.1159/000495935
NING Y C , HUI N , QING B , et al . ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation [J ] . Cell Death Dis , 2019 , 10 ( 6 ): 414 . DOI: 10.1038/s41419-019-1635-9 http://doi.org/10.1038/s41419-019-1635-9
SHAO L P , ZUO X L , YANG Y , et al . The inherited variations of a p53-responsive enhancer in 13q12.12 confer lung cancer risk by attenuating TNFRSF19 expression [J ] . Genome Biol , 2019 , 20 ( 1 ): 103 . DOI: 10.1186/s13059-019-1696-1 http://doi.org/10.1186/s13059-019-1696-1
REN S X , ZHANG S C , JIANG T , et al . Early detection of lung cancer by using an autoantibody panel in Chinese population [J ] . Oncoimmunology , 2018 , 7 ( 2 ): e1384108 . DOI: 10.1080/2162402X.2017.1384108 http://doi.org/10.1080/2162402X.2017.1384108 https://www.tandfonline.com/doi/full/10.1080/2162402X.2017.1384108 https://www.tandfonline.com/doi/full/10.1080/2162402X.2017.1384108
WEN W , LIU G , JIN K , et al . TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells [J ] . Oncol Rep , 2017 , 37 ( 1 ): 115 - 122 . DOI: 10.3892/or.2016.5238 http://doi.org/10.3892/or.2016.5238
LIN S C , CHOU Y T , JIANG S S , et al . Epigenetic switch between SOX2 and SOX9 regulates cancer cell plasticity [J ] . Cancer Res , 2016 , 76 ( 23 ): 7036 - 7048 . DOI: 10.1158/0008-5472.CAN-15-3178 http://doi.org/10.1158/0008-5472.CAN-15-3178 https://aacrjournals.org/cancerres/article/76/23/7036/613967/Epigenetic-Switch-between-SOX2-and-SOX9-Regulates https://aacrjournals.org/cancerres/article/76/23/7036/613967/Epigenetic-Switch-between-SOX2-and-SOX9-Regulates
KAMEL L M , ATEF D M , MACKAWY A M H , et al . Circulating long non-coding RNA GAS5 and SOX2OT as potential biomarkers for diagnosis and prognosis of non-small cell lung cancer [J ] . Biotechnol Appl Biochem , 2019 , 66 ( 4 ): 634 - 642 . DOI: 10.1002/bab.1764 http://doi.org/10.1002/bab.1764 https://onlinelibrary.wiley.com/doi/10.1002/bab.1764 https://onlinelibrary.wiley.com/doi/10.1002/bab.1764
TANG Z M , LING Z G , WANG C M , et al . Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: a systematic review and meta-analysis [J ] . PLoS One , 2017 , 12 ( 7 ): e0182117 . DOI: 10.1371/journal.pone.0182117 http://doi.org/10.1371/journal.pone.0182117 https://dx.plos.org/10.1371/journal.pone.0182117 https://dx.plos.org/10.1371/journal.pone.0182117
MU Y Y , XIE F Y , WANG F B , et al . Performance evaluation of an enzyme-linked immunosorbent assay for seven autoantibodies in lung cancer [J ] . Clin Lab , 2019 , 65 ( 4 ).
FANIPAKDEL A , SEILANIAN TOUSSI M , REZAZADEH F , et al . Overexpression of cancer-testis antigen melanoma-associated antigen A1 in lung cancer: a novel biomarker for prognosis, and a possible target for immunotherapy [J ] . J Cell Physiol , 2019 , 234 ( 7 ): 12080 - 12086 . DOI: 10.1002/jcp.27884 http://doi.org/10.1002/jcp.27884
0
Views
2309
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621