Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (10): 33-41.doi: 10.6040/j.issn.1671-7554.0.2022.0169

Previous Articles     Next Articles

Proteomic analysis of serum exosomes in pancreatic cancer with different stages of progress

LI Yanru, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin   

  1. Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2022-09-30

PDF (PC)

230

Abstract: Objective To screen the differential proteins of serum exosomes in healthy controls and pancreatic cancer patients with different degrees of progression, draw the profile, and analyze their functions and biological processes. Methods Exosomes were quantitatively analyzed with label-free quantitative proteomic analysis technology. The differential proteins were screened and bioinformatic analysis was performed. The proteins associated with pancreatic cancer progression were serologically verified with Western blotting. Results A total of 2 242 proteins were detected in the control, non-metastatic and metastatic pancreatic cancer samples with label-free quantitative proteomic analysis and a total of 664 proteins with statistically significant differences were identified, which were mainly involved in vesicle-mediated transport, focal adhesion and extracellular cortex matrix(ECM)receptor interaction. Moreover, there were 5 proteins with statistically significant differences among the three groups, of which leucine-rich alpha-2-glycoprotein 1(LRG1)was highly expressed in serum exosomes of metastatic pancreatic cancer. Conclusion There are differences in protein expression patterns among healthy controls, non-metastatic and metastatic pancreatic cancer patients, and the differential proteins are mainly enriched in focal adhesion and ECM-receptor interaction and other signaling pathways. LRG1, which is different in all three groups, may be a serological marker for monitoring the progression of pancreatic cancer.

Key words: Pancreatic cancer, Exosome, Proteomics, Bioinformatics, Leucine-rich alpha-2-glycoprotein 1

CLC Number: 

  • R735.9
[1] Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(7):493-502.
[2] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[3] Vincent A, Herman J, Schulick R, et al. Pancreatic cancer[J]. Lancet, 2011, 378(9791): 607-620.
[4] Jiang K, Chen H, Fang Y, et al. Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness[J]. J Exp Clin Cancer Res, 2021, 40(1): 21.
[5] Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response[J]. Nature, 2018, 560(7718): 382-386.
[6] 韩柳, 孙宇. 胞外囊泡与癌症[J]. 中国细胞生物学学报, 2016, 38(4): 347-355. HAN Liu, SUN Yu. Extracellular vesicles and cancer[J]. Chinese Journal of Cell Biology, 2016, 38(4): 347-355.
[7] Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J]. Nature, 2015, 523(7559): 177-182.
[8] Liu Z, Liu Y, Qian L, et al. A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies[J]. Mol Cell, 2021, 81(19): 4076-4090.
[9] Liu J, Yuan B, Cao J, et al. Ambra1 promotes TGFbeta signaling via nonproteolytic polyubiquitylation of smad4[J]. Cancer Res, 2021, 81(19): 5007-5020.
[10] Wu J, Gao W, Tang Q, et al. M2 macrophage-derived exosomes facilitate HCC metastasis by transferring alphaM beta2 integrin to tumor cells[J]. Hepatology, 2021, 73(4): 1365-1380.
[11] Wang D, Zhao C, Xu F, et al. Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2[J]. Theranostics, 2021, 11(6): 2860-2875.
[12] Yuan X, Qian N, Ling S, et al. Breast cancer exosomes contribute to pre-metastatic niche formation and promote bone metastasis of tumor cells[J]. Theranostics, 2021, 11(3): 1429-1445.
[13] Wang S, Xu M, Li X, et al. Exosomes released by hepatocarcinoma cells endow adipocytes with tumor-promoting properties[J]. J Hematol Oncol, 2018, 11(1): 82.
[14] Yoon JH, Ashktorab H, Smoot DT, et al. Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells[J]. Gastric Cancer, 2020, 23(5): 848-862.
[15] Repetto O, De Re V, Giuffrida P, et al. Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer[J]. Gastric Cancer, 2021, 24(3): 666-679.
[16] Thakur R, Singh PK. Molecular subtypes of pancreatic cancer: a proteomics approach[J]. Clin Cancer Res, 2021, 27(12): 3272-3274.
[17] Kugeratski FG, Hodge K, Lilla S, et al. Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker[J]. Nat Cell Biol, 2021, 23(6): 631-641.
[18] Yang J, Zhang Y, Gao X, et al. Plasma-derived exosomal ALIX as a novel biomarker for diagnosis and classification of pancreatic cancer[J]. Front Oncol, 2021, 11: 628346. doi: 10.3389/fonc.2021.628346.
[19] Han S, Huo Z, Nguyen K, et al. The proteome of pancreatic cancer-derived exosomes reveals signatures rich in key signaling pathways[J]. Proteomics, 2019, 19(13): e1800394. doi: 10.1002/pmic.201800394.
[20] Castillo J, Bernard V, San Lucas FA, et al. Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients[J]. Ann Oncol, 2018, 29(1): 223-229.
[21] Shi X, Guo X, Li X, et al. Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover[J]. Cancer Lett, 2018, 433: 76-85. doi: 10.1016/j.canlet.2018.06.015.
[22] Okamoto H, Kusama T, Fujii H. Tyrosine phosphorylation of focal adhesion anchoring proteins enhances human pancreatic cancer cell invasion[J]. Pancreas, 2016, 45(7): 37-39.
[23] Wang X, Luo G, Zhang K, et al. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kgamma to promote pancreatic cancer metastasis[J]. Cancer Res, 2018, 78(16): 4586-4598.
[24] Yang B, Feng X, Liu H, et al. High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma[J]. Oncogene, 2020, 39(42): 6529-6543.
[25] Chen Q, Yu D, Zhao Y, et al. Screening and identification of hub genes in pancreatic cancer by integrated bioinformatics analysis[J]. J Cell Biochem, 2019, 120(12): 19496-19508.
[26] Chen S, Gao C, Yu T, et al. Bioinformatics analysis of a prognostic miRNA signature and potential key genes in pancreatic cancer[J]. Front Oncol, 2021, 11: 641289. doi: 10.3389/fonc.2021.641289.
[27] Singhal M, Gengenbacher N, Abdul Pari AA, et al. Temporal multi-omics identifies LRG1 as a vascular niche instructor of metastasis[J]. Sci Transl Med, 2021, 13(609): eabe6805. doi: 10.1126/scitranslmed.abe6805.
[28] He L, Feng A, Guo H, et al. LRG1 mediated by ATF3 promotes growth and angiogenesis of gastric cancer by regulating the SRC/STAT3/VEGFA pathway[J]. Gastric Cancer, 2022, 25(3): 527-541.
[29] Zhong B, Cheng B, Huang X, et al. Colorectal cancer-associated fibroblasts promote metastasis by up-regulating LRG1 through stromal IL-6/STAT3 signaling[J]. Cell Death Dis, 2021, 13(1): 16. doi: 10.1038/s41419-021-04461-6.
[1] LIU Teng, MA Yingchun. Expression of ECT2 in uterine corpus endometrial carcinoma and its clinical significance based on bioinformatics database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 63-71.
[2] YUAN Baowen, WANG Pei, HUANG Wei. Regulatory role of histone deacetylase SIRT1 in pancreatic cancer metabolism [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 1-12.
[3] CHEN Lixiao, YING Xinjiang, CHEN Xinwei, WANG Fei, SUN Zhenfeng, DONG Pin. Identification of proteins in hypopharyngeal squamous cell carcinoma by mass spectrometry and screening of prognostic target molecules [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 140-147.
[4] ZHANG Gaorui, ZHANG Yuting, ZHAO Yuxuan, WANG Fangqing, YU Dexin. Value of MnFe2O4@CNS in the theragnostic of pancreatic cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 48-55.
[5] HUA Fang, ZHANG Weiwei, LYU Bo, XIN Wei. Bioinformatic analysis of genes and molecular pathways associated with osteoarthritis synovitis [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 10-17.
[6] LI Canxuan, CHEN Jie. Expression and activity mechanism of acetyl-CoA acyltransferase 1 in clear cell renal cell carcinoma based on bioinformatics [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 26-33.
[7] WANG Yan, ZHANG Yuhui, HU Naibo, TENG Guangshuai, ZHOU Yuan, BAI Jie. Characteristics of bone marrow immune microenvironment in patients with acute myeloid leukemia based on single-cell RNA sequencing [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 32-40.
[8] DU Tiantian, LI Juan, ZHAO Yinghui, DUAN Weili, WANG Jing, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression profiles of long non-coding RNA LINC02474 and effects on cell proliferation in colorectal cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 59-69.
[9] LI Yinglin, SONG Daoqing, XU Zhonghua. Identification of FKBP11 expression in clear cell renal cell carcinoma using bioinformatics analysis [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 45-51.
[10] TIAN Baorui, ZHANG Yongchao, HAN Xiaoyang, TIAN Yingying, WANG Chuanxi. Prediction of the association between genes and glioblastoma based on databases [J]. Journal of Shandong University (Health Sciences), 2020, 58(6): 8-13.
[11] LIU Xiaojing, XIA Xiyan, XIAO Ke, CHEN Wendan, ZHUANG Xuewei. Expression and clinical significance of exosomal long non-coding RNA OGFRP1 in 84 cases of non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 71-75.
[12] WANG Guoyun, YUAN Ming, JI Miaomiao. Research advances in the pathogenesis of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 33-39.
[13] WANG Chuanxin. Research progress of exosomes biomarkers in tumor development [J]. Journal of Shandong University (Health Sciences), 2018, 56(10): 18-23.
[14] ZHOU Jian, ZHAO Hanting, LÜ Gang, WANG Lin, LI Qihang, ZHU Meiyan, WANG Zhilin, HE Shenyi. Bioinformatics analysis and construction of an eukaryocyte vector of ROP19 protein in Toxoplasma gondii [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(3): 64-69.
[15] XU Yujun, LIU Ming, HE Xiangmeng, LI Chengli. 1.0T open MRI-guided 125I seeds percutaneous implantation for advanced pancreatic cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(2): 21-25.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1 -6 .
[2] LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde. Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 15 -23 .
[3] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
[4] ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong. miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 7 -14 .
[5] FU Jieqi, ZHANG Man, ZHANG Xiaolu, LI Hui, CHEN Hong. Molecular mechanism of Toll-like receptor 4 in the aggravation of blood lipid accumulation by inhibiting the peroxisome proliferator-activate receptor γ[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 24 -31 .
[6] XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng. A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 67 -71 .
[7] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[8] XIAO Juan, XIAO Qiang, CONG Wei, LI Ting, DING Shouluan, ZHANG Yuan, SHAO Chunchun, WU Mei, LIU Jianing, JIA Hongying. Comparison of diagnostic efficacy of two kinds of thyroid imagine reporting and data systems[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 53 -59 .
[9] LI Songlin, LIU Peilai, LU Qunshan, MA Heran. Application of high tibial osteotomy combined with autologous adipose-derived mesenchymal stem cells injection in the repair of knee cartilage[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 82 -88 .
[10] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd