RNA结合蛋白PTBP1与磷酸化-AXL共表达在骨肉瘤中的临床意义
Clinical Significance of co-expression of RNA Binding Protein PTBP1 and p-AXL in Osteosarcoma
- 中山大学学报（医学科学版） 2023年44卷第3期 页码：446-455
- 作者机构：
中山大学附属第一医院病理科，广东 广州，510080
- 作者简介：
李湘湘，硕士生，研究方向：骨肿瘤病理，E-mail： 971024742@qq.com
徐雯莉，并列第一作者，硕士生，研究方向：骨肿瘤病理，xuwli3@mail2.sysu.edu.cn
- 基金信息：国家自然科学基金(81872175)
DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0311
中图分类号： R738.1纸质出版日期：2023-05-20，
收稿日期：2023-01-02，
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李湘湘,徐雯莉,卢正宇等.RNA结合蛋白PTBP1与磷酸化-AXL共表达在骨肉瘤中的临床意义[J].中山大学学报（医学科学版）,2023,44(03):446-455.
LI Xiang-xiang,XU Wen-li,LU Zheng-yu,et al.Clinical Significance of co-expression of RNA Binding Protein PTBP1 and p-AXL in Osteosarcoma[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):446-455.
李湘湘,徐雯莉,卢正宇等.RNA结合蛋白PTBP1与磷酸化-AXL共表达在骨肉瘤中的临床意义[J].中山大学学报（医学科学版）,2023,44(03):446-455. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0311.
LI Xiang-xiang,XU Wen-li,LU Zheng-yu,et al.Clinical Significance of co-expression of RNA Binding Protein PTBP1 and p-AXL in Osteosarcoma[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):446-455. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0311.
摘要
目的
2
探索RNA结合蛋白PTBP1与p-AXL在骨肉瘤中的表达情况及其临床病理联系，并进一步探讨PTBP1/p-AXL共表达在骨肉瘤中的预后评估意义。
方法
2
应用GEO和Target数据库分析PTBP1与AXL在骨肉瘤和正常组织中的表达差异及PTBP1的预后价值。收集2016年3月至2020年10月中山大学第一附属医院76例骨肉瘤和37例非恶性骨组织（骨痂、骨纤维结构不良或骨样骨瘤）及其病例信息，应用免疫组化法检测PTBP1和p-AXL蛋白的表达情况并行统计学分析。
结果
2
GEO数据库分析结果显示PTBP1和AXL在骨肉瘤组织的表达具有高于正常组织的趋势，但尚未达到统计学意义；Target数据分析结果显示PTBP1高表达组骨肉瘤患者总生存期（OS）与无进展生存期（PFS）均短于低表达组，但差异尚未达统计学意义（
P
=0.064；
P
=0.134）。免疫组化结果显示PTBP1和p-AXL蛋白的表达在骨肉瘤组织中显著高于非恶性骨组织；p-AXL阳性表达率与肺转移相关（
P
=0.025）；Kaplan-Meier分析发现肺转移、复发、PTBP1表达及PTBP1/p-AXL共表达等因素与骨肉瘤患者不良总生存期相关；且多变量Cox回归分析显示肺转移（
P
<
0.000 1）、PTBP1表达阳性（
P
=0.041）是骨肉瘤患者总生存期（OS）独立危险因素；PTBP1/p-AXL共表达患者的OS（
P
=0.017）和PFS（
P
=0.043）均低于非PTBP1/p-AXL共表达患者。
结论
2
PTBP1、p-AXL在骨肉瘤中高表达，PTBP1与p-AXL共表达与患者预后差相关，且PTBP1可作为骨肉瘤患者独立预后指标。
Abstract
Objective
2
To explore the co-expression of PTBP1 and p-AXL in osteosarcoma and its clinicopathological significance for prognosis evaluation.
Methods
2
The expression of PTBP1 and AXL and their prognostic value in osteosarcoma were analyzed by GEO and Target data. Paraffin biopsy specimens and clinical information from 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue （callus， osteofibrous dysplasia and osteoid ostema） were obtained from the First Affiliated Hospital of Sun Yat-sen University from March 2016 to October 2020. The expressions of PTBP1 and p-AXL proteins in osteosarcoma were detected by immunohistochemistry.
Results
2
GEO database showed that the expression levels of PTBP and AXL in osteosarcoma tumor group were higher than those in normal tissues， but did not reach statistical significance. Target database showed that the high expression of PTBP1 had shorter Overall survival（OS） and Progression-free survival（PFS） than low PTBP1 expression， but did not reach statistical significance （
P
=0.064；
P
=0.134）. Immunohistochemical staining included 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue. The expression rate of PTBP1 and p-AXL protein in osteosarcoma tissues was higher than that in non-malignant bone tissue. The expression of p-AXL is correlated with lung metastasis （
P
=0.025）. Kaplan-Meier analysis showed that lung metastasis， recurrence， PTBP1 expression， co-expression of PTBP1/p-AXL influence the prognosis of patients in OS. Multivariate Cox regression analysis showed that lung metastasis （
P
<
0.000 1） and positive expression of PTBP1 （
P
=0.041） were independent risk factors for osteosarcoma patients in OS. Co-expression of PTBP1 and p-AXL had shorter OS （
P
=0.017） and PFS （
P
=0.043） than non-coexpression osteosarcoma patients.
Conclusions
2
PTBP1 and p-AXL were highly expressed in osteosarcoma tissues. The co-expression of PTBP1 and p-AXL was associated with poor prognosis of patients， and PTBP1 could be used as an independent prognostic indicator of patients with osteosarcoma.
关键词
骨肉瘤多聚嘧啶区结合蛋白1受体酪氨酸激酶预后
Keywords
osteosarcomaPTBP1p-AXLprognosis
references
Ottaviani G， Jaffe N. The epidemiology of osteosarcoma［J］. Cancer Treat Res， 2009， 152： 3-13.
Mirabello L， Troisi RJ， Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004： data from the Surveillance， Epidemiology， and End Results Program［J］. Cancer， 2009， 115（7）： 1531-1543.
Sadykova LR， Ntekim AI， Muyangwa-semenova M， et al. Epidemiology and risk factors of osteosarcoma［J］. Cancer Invest， 2020， 38（5）： 259-269.
Eaton BR， Schwarz R， Vatner R， et al. Osteosarcoma［J］. Pediatr Blood Cancer， 2021， 68（S2）： e28352.
Gill J， Gorlick R. Advancing therapy for osteosarcoma［J］. Nat Rev Clin Oncol， 2021， 18（10）： 609-624.
Keppetipola N， Sharma S， Li Q， et al. Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins， PTBP1 and PTBP2［J］. Crit Rev Biochem Mol Biol， 2012， 47（4）： 360-378.
Shan H， Hou P， Zhang M， et al. PTBP1 knockdown in renal cell carcinoma inhibits cell migration， invasion and angiogenesis in vitro and metastasis in vivo via the hypoxia inducible factor-1alpha pathway［J］. Int J Oncol， 2018， 52（5）： 1613-1622.
Cui J， Placzek WJ. PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics［J］. Cell Death Differ， 2016， 23（10）： 1681-1690.
Wang X， Li Y， Fan Y， et al. PTBP1 promotes the growth of breast cancer cells through the PTEN/Akt pathway and autophagy［J］. J Cell Physiol， 2018， 233（11）： 8930-8939.
Yao XY， Liu JF， Luo Y， et al. LncRNA HOTTIP facilitates cell proliferation， invasion， and migration in osteosarcoma by interaction with PTBP1 to promote KHSRP level［J］. Cell Cycle， 2021， 20（3）： 283-297.
O'bryan JP， Frye RA， Cogswell PC， et al. Axl， a transforming gene isolated from primary human myeloid leukemia cells， encodes a novel receptor tyrosine kinase［J］. Mol Cell Biol， 1991， 11（10）： 5016-5031.
Wang C， Jin H， Wang N， et al. Gas6/Axl axis contributes to chemoresistance and metastasis in breast cancer through Akt/GSK-3beta/beta-catenin signaling［J］. Theranostics， 2016， 6（8）： 1205-1219.
Goruppi S， Ruaro E， Varnum B， et al. Requirement of phosphatidylinositol 3-kinase-dependent pathway and Src for Gas6-Axl mitogenic and survival activities in NIH 3T3 fibroblasts［J］. Mol Cell Biol， 1997， 17（8）： 4442-4453.
Han J， Tian R， Yong B， et al. Gas6/Axl mediates tumor cell apoptosis， migration and invasion and predicts the clinical outcome of osteosarcoma patients［J］. Biochem Biophys Res Commun， 2013， 435（3）： 493-500.
Harrison DJ， Geller DS， Gill JD， et al. Current and future therapeutic approaches for osteosarcoma［J］. Expert Rev Anticancer Ther， 2018， 18（1）： 39-50.
Sawicka K， Bushell M， Spriggs K， et al. Polypyrimidine-tract-binding protein： a multifunctional RNA-binding protein［J］. Biochem Soc Trans， 2008， 36（4）： 641-647.
Zhang Q， Wu J， Zhang X， et al. Transcription factor ELK1 accelerates aerobic glycolysis to enhance osteosarcoma chemoresistance through miR-134/PTBP1 signaling cascade［J］. Aging， 2021， 13（5）： 6804-6819.
Li JJ， Xiong MY， Sun TY， et al. CircFAM120B knockdown inhibits osteosarcoma tumorigenesis via the miR-1205/PTBP1 axis［J］. Aging， 2021， 13（20）： 23831-23841.
Gong H， Jiang A， Jiang R， et al. PTBP1 as a promising predictor of poor prognosis by regulating cell proliferation， immunosuppression， and drug sensitivity in SARC［J］. Oxid Med Cell Longev， 2022： 5687238.
Duan L， Wang J， Zhang D， et al. Immune-related miRNA-195-5p inhibits the progression of lung adenocarcinoma by targeting polypyrimidine tract-binding protein 1［J］. Front Oncol， 2022， 12： 862564.
Huan L， Guo T， Wu Y， et al. Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response［J］. Mol Cancer， 2020， 19（1）： 11.
Taniguchi K， Uchiyama K， Akao Y. PTBP1-targeting microRNAs regulate cancer-specific energy metabolism through the modulation of PKM1/M2 splicing［J］. Cancer Sci， 2021， 112（1）： 41-50.
Lemke G. Biology of the TAM receptors［J］. Cold Spring Harb Perspect Biol， 2013， 5（11）： a9076.
Zhan Z， Ji Y， Su H， et al. Discovery of 10H-benzo［b］pyrido［2，3-e］［1，4］oxazine AXL Inhibitors via structure-based drug design targeting c-met kinase［J］. J Med Chem， 2023， 66（1）： 220-234.
Goyette MA， Duhamel S， Aubert L， et al. The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression［J］. Cell Rep， 2018， 23（5）： 1476-1490.
Rankin EB， Fuh KC， Taylor TE， et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer［J］. Cancer Res， 2010， 70（19）： 7570-7579.
Wu PK， Chen WM， Chen CF， et al. Primary osteogenic sarcoma with pulmonary metastasis： clinical results and prognostic factors in 91 patients［J］. Jpn J Clin Oncol， 2009， 39（8）： 514-522.
Li Q， Wang X， Jiang N， et al. Exosome-transmitted linc00852 associated with receptor tyrosine kinase AXL dysregulates the proliferation and invasion of osteosarcoma［J］. Cancer Med， 2020， 9（17）： 6354-6366.
Cho CY， Chung SY， Lin S， et al. PTBP1-mediated regulation of AXL mRNA stability plays a role in lung tumorigenesis［J］. Sci Rep， 2019， 9（1）： 16922.
Shen L， Lei S， Zhang B， et al. Skipping of exon 10 in Axl pre-mRNA regulated by PTBP1 mediates invasion and metastasis process of liver cancer cells［J］. Theranostics， 2020， 10（13）： 5719-5735.
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