bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–10–23
fourteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes Derived from Hypoxic Glioma Cells Reduce the Sensitivity of Glioma Cells to Temozolomide Through Carrying miR-106a-5p.
  2. Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization.
  3. The emerging roles of exosome-derived noncoding RNAs in the tumor immune microenvironment and their future applications.
  4. Strategies to overcome the main challenges of the use of exosomes as drug carrier for cancer therapy.
  5. Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1.
  6. Exosomal microRNAs mediating crosstalk between cancer cells and cancer-associated fibroblasts in the tumor microenvironment.
  7. Plasma Exosomal CXCL7 is a Potential Biomarker for Lung Adenocarcinoma.
  8. NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer.
  9. Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.
  10. The role of exosomes in the molecular mechanisms of metastasis: Focusing on EMT and cancer stem cells.
  11. The diagnostic role and mechanistic functions of exosomal lncRNAs in prostate cancer.
  12. Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection.
  13. Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer.
  14. Identification of the Level of Exosomal Protein by Parallel Reaction Monitoring Technology in HCC Patients.
  1. Drug Des Devel Ther. 2022 ;16 3589-3598
    Exosomes Derived from Hypoxic Glioma Cells Reduce the Sensitivity of Glioma Cells to Temozolomide Through Carrying miR-106a-5p.
    Peizhang Wu, Jun Guo, Hongwei Yang, Debin Yuan, Chaoxiang Wang, Zhong Wang.
       Background: Hypoxia is a frequent feature of solid tumors which significantly affects the efficacy of treatments such as chemotherapy. In addition, exosomes from hypoxic cancer cells could contribute to the chemoresistance of tumor cells through carrying miRNAs. It has been shown that miR-106-5p level was upregulated in glioma. However, whether exosomes derived from hypoxic glioma cells could affect temozolomide (TMZ) resistance in glioma through carrying miR-106a-5p remains unexplored.
    Methods: Exosomes were isolated from glioma cells under normoxia or hypoxia condition. EdU staining and flow cytometry assays were used to assess the cell proliferation and cell apoptosis. The relation between miR-106a-5p and PTEN was investigated by dual luciferase assay.
    Results: MiR-106a-5p was enriched in exosomes derived from hypoxic glioma cells compared to exosomes from cells under normoxia condition. Additionally, hypoxic glioma cells were able to transfer exosomes to glioma cells, resulting in a significant increase of miR-106a-5p level in cells. TMZ remarkably suppressed glioma cell proliferation and triggered cell apoptosis. However, hypoxic glioma cell-derived exosomes markedly promoted the proliferation and suppressed the apoptosis in TMZ-treated glioma cells, and miR-106a-5p inhibitor was able to abolish these phenomena. Meanwhile, PTEN was verified to be a direct target of miR-106a-5p. Furthermore, TMZ elevated PTEN and Bax level and reduced p-Akt level in glioma cells, whereas these changes were reversed by hypoxia glioma cell-derived exosomes. Furthermore, hypoxia glioma cell-derived exosomes reduced the sensitivity of glioma cells to TMZ in vivo via downregulating PTEN.
    Conclusion: Collectively, exosomal miR-106a-5p derived from hypoxia glioma cells could reduce the sensitivity of glioma cells to TMZ through downregulating PTEN. Thus, our study might provide new strategies for improving the clinical efficacy of TMZ on glioma.
    Keywords:  cancer; chemosensitivity; hypoxia; miR-106a-5p
    DOI:  https://doi.org/10.2147/DDDT.S382690
  2. Eur J Histochem. 2022 Oct 14. 66(4):
    Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization.
    Jiangmu Chen, Zongchi Chen, Weitao Hu, Daxing Cai.
      Esophageal carcinoma (EC) is a highly malignant type of tumor. In a previous study, the authors found that long non-coding RNA (lncRNA) LOC441178 inhibited the tumorigenesis of EC. Moreover, exosomes derived from tumor cells containing lncRNAs were found to play a key role in the tumor environment; however, whether exosomes can affect the tumor microenvironment by carrying LOC441178 remains unclear. Thus, the present study aimed to clarify this. In order to assess the effects of exosomal LOC441178 in EC, cell invasion and migration were examined using the Transwell assay. Exosomes were identified using transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. Furthermore, macrophage surface makers (CD206 and CD86) were analyzed using flow cytometry. Moreover, a subcutaneous xenograft mouse model was constructed to assess the role of TE-9 cells-derived exosomal LOC441178 in EC. The results revealed that LOC441178 overexpression notably suppressed the metastasis of EC cells. In addition, exosomes were successfully isolated from EC cells, and LOC441178 level was upregulated in exosomes derived from LOC441178-overexpressed EC cells. Exosomal LOC441178 also suppressed macrophage M2 polarization, and the polarized macrophages decreased EC cell invasion. Exosomes containing LOC441178 notably inhibited the growth of EC in mice. On the whole, the present study demonstrated that the delivery of LOC441178 by EC cell-secreted exosomes inhibited the tumorigenesis of EC by suppressing the polarization of M2 macrophages. These findings may provide a new theoretical basis for discovering new strategies against EC.
    DOI:  https://doi.org/10.4081/ejh.2022.3510
  3. Biomed Pharmacother. 2022 Oct 13. pii: S0753-3322(22)01252-5. [Epub ahead of print]156 113863
    The emerging roles of exosome-derived noncoding RNAs in the tumor immune microenvironment and their future applications.
    Fang Wei, Yan Li.
      Exosomes are a major subgroup of extracellular vesicles (EVs) generated through the endosomal pathways in the endosomal sorting complex required for the transport in endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent manner. Natural EVs carry various biological materials, including proteins, lipids, nucleic acids and metabolic waste, and act as messengers that mediate multifarious biofunctions. Noncoding RNAs (ncRNAs) are an essential type of EV cargo. Current immunotherapies represented by immune checkpoint blockade have emerged as an important option for tumor treatment. However, our understanding of how cells of the tumor immune microenvironment interact with each other is relatively poor. Thus, we review the current knowledge about the role of exosomal ncRNAs in the tumor immune microenvironment.
    Keywords:  Exosomes; Extracellular vesicles; Immunity; Noncoding RNAs; Tumor; Tumor immune microenvironment
    DOI:  https://doi.org/10.1016/j.biopha.2022.113863
  4. Cancer Cell Int. 2022 Oct 18. 22(1): 323
    Strategies to overcome the main challenges of the use of exosomes as drug carrier for cancer therapy.
    Bashdar Mahmud Hussen, Goran Sedeeq Hama Faraj, Mohammad Fatih Rasul, Hazha Jamal Hidayat, Abbas Salihi, Aria Baniahmad, Mohammad Taheri, Soudeh Ghafouri-Frad.
      Exosomes are naturally occurring nanosized particles that aid intercellular communication by transmitting biological information between cells. Exosomes have therapeutic efficacy that can transfer their contents between cells as natural carriers. In addition, the exosomal contents delivered to the recipient pathological cells significantly inhibit cancer progression. However, exosome-based tumor treatments are inadequately precise or successful, and various challenges should be adequately overcome. Here, we discuss the significant challenges that exosomes face as drug carriers used for therapeutic targets and strategies for overcoming these challenges in order to promote this new incoming drug carrier further and improve future clinical outcomes. We also present techniques for overcoming these challenges.
    Keywords:  Cancer therapy; Drug carrier; Exosomal delivery challenges; Exosome
    DOI:  https://doi.org/10.1186/s12935-022-02743-3
  5. Front Oncol. 2022 ;12 1021270
    Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1.
    Han Guan, Likai Mao, Jinfeng Wang, Sheng Wang, Shuai Yang, Hongliang Wu, Wenyan Sun, Zhijun Chen, Ming Chen.
       Background: Exosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa patients' exosomes, but the role of exosomal RNF157 mRNA in PCa development remains unclear.
    Methods: Online databases were utilized for predicting gene expression and binding correlation between different factors. RT-qPCR and western blot assays were respectively done to analyze RNA and protein expressions. Flow cytometry analysis was implemented to analyze M2 polarization.
    Results: RNF157 expression was high in PCa tissues and cells. M2 polarization of macrophages was enhanced after co-culture with PCa cells or with exosomes released by PCa cells. Upon RNF157 knockdown in PCa cells, the extracted exosomes could not lead to the facilitated M2 polarization. Mechanistically, RNF157 could bind to HDAC1 and contribute to HDAC1 ubiquitination, which led to HDAC1 degradation and resulting in promoting M2 polarization of macrophages. Animal experiments validated that exosomal RNF157 accelerated PCa tumor growth through facilitating macrophage M2 polarization.
    Conclusion: Exosome-mediated RNF157 mRNA from PCa cells results in M2 macrophage polarization via destabilizing HDAC1, consequently promoting PCa tumor progression.
    Keywords:  HDAC1; M2 macrophage polarization; exosomal RNF157 mRNA; prostate cancer; ubiquitination
    DOI:  https://doi.org/10.3389/fonc.2022.1021270
  6. Pathol Res Pract. 2022 Oct 10. pii: S0344-0338(22)00403-4. [Epub ahead of print]239 154159
    Exosomal microRNAs mediating crosstalk between cancer cells and cancer-associated fibroblasts in the tumor microenvironment.
    Yongfang Wang, Hanyun Liang, Jie Zheng.
       PURPOSE: Cancer-associated fibroblasts (CAFs) play an important role in tumor formation and development by serving as the most influential stromal cells within the tumor microenvironment (TME). The communication between tumor cells and CAFs, along with the resulting impact, is more important than originally anticipated. Numerous studies have demonstrated that microRNAs (miRNAs) play an essential role in this crosstalk, and related evidence continues to emerge and advance. In addition, exosomes containing miRNAs have been found as a crucial mode of interaction between these two types of cells, with a more direct and precise role. Under the influence of exosomal miRNAs, normal fibroblasts are converted into CAFs. By doing so, CAFs can greatly promote tumor progression. Additionally, through exosomal miRNAs, activated CAFs may alter the genetic expression in tumor cells, affecting the TME and promoting malignant biological processes. Learning more about exosomal miRNAs in tumor cells and CAFs, and the intricate molecular networks that link CAFs to cancer cells, may help researchers develop more sensitive and effective cancer treatments targeting miRNAs, exosomes and CAFs, thereby giving hope to cancer patients.
    METHODS: A comprehensive search of the literature was conducted through PubMed databases. The keywords entered for the search included: exosomes, cancer-associated fibroblasts, microRNA and cancer. This search provided information about articles published in peer-reviewed journals until 2022. Information from these articles was collected and analyzed in this review.
    RESULTS: Exosomal miRNAs can act as tumor inhibitors or tumor inducers by affecting several targets and molecular signaling pathways. MiRNAs and exosomes involved in crosstalk could have promising applications in cancer diagnosis, prognosis, and therapy.
    CONCLUSION: This finding about the crosstalk can help find and develop innovative miRNA-based approaches towards diagnosis, prognosis, and anti-cancer treatments.
    Keywords:  Cancer-associated fibroblasts; Exosomes; MicroRNA·Cancer
    DOI:  https://doi.org/10.1016/j.prp.2022.154159
  7. Clin Lab. 2022 Oct 01. 68(10):
    Plasma Exosomal CXCL7 is a Potential Biomarker for Lung Adenocarcinoma.
    Wenting Fang, Jianbin You, Qifeng Xu, Yingfeng Jiang, Haizhou Hu, Falin Chen, Liangyuan Chen.
       BACKGROUND: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies.
    METHODS: The differential expression profile of plasma exosomal mRNA was established by high-throughput sequencing, and the expression and diagnostic value of plasma exosomal CXCL7 mRNA and protein in LUAD were studied to evaluate their diagnostic value as tumor biomarkers.
    RESULTS: The expression of plasma exosomal CXCL7 mRNA in patients with LUAD was significantly increased (p < 0.01), which had no significant correlation with age, gender, and stage. ROC was used to evaluate the diagnostic value of plasma exosomal CXCL7 mRNA in LUAD patients with AUC = 0.7171. Further analysis signified that the CXCL7 protein of plasma exosomes in LUAD patients was overexpressed, and it was positively correlated with TNM stage and age. The diagnostic value of plasma exosomal CXCL7 in LUAD is better than serum CEA, with an AUC of 0.785, which has higher sensitivity and specificity.
    CONCLUSIONS: This research suggests that plasma exosomal CXCL7 may become an effective biomarker for early diagnosis of LUAD.
    DOI:  https://doi.org/10.7754/Clin.Lab.2022.220128
  8. Cell Death Dis. 2022 Oct 21. 13(10): 891
    NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer.
    Xinrui Rao, Xiaoshu Zhou, Geng Wang, Xiaohua Jie, Biyuan Xing, Yingzhuo Xu, Yunshang Chen, Jun Li, Kuikui Zhu, Zilong Wu, Gang Wu, Chuangyan Wu, Rui Zhou.
      Metastasis remains the primary cause of small cell lung cancer (SCLC)-related deaths. Growing evidence links tumor metastasis with a pre-metastatic microenvironment characterized by an anti-inflammatory response, immunosuppression, and the presence of tumor-derived exosomes. To clarify the relationships among these factors in SCLC, we analyzed SCLC patient samples as well as a mouse model. Among the infiltrating immune cells, our study focused on the tumor-associated macrophages (TAMs), that are well-known to promote tumor progression and metastasis. We found that high expression of the alternatively activated (M2) TAM marker, CD206+ was associated clinically with a poorer prognosis and metastasis state in patients with SCLC. Moreover, infiltrating macrophages (MØ) were found in the metastatic foci of an SCLC mouse model. Additionally, we observed dominant switching to M2 phenotype, accompanied by increased NLRP6 expression. Since tumor-derived exosomes are the key links between the tumor and its immune microenvironment, we further investigated whether SCLC-derived exosomes contributed to the MØ phenotype switch. Our findings showed for the first time that SCLC-derived exosomes induce the M2 switch via the NLRP6/NF-κB pathway, and thus, promote SCLC metastasis in vitro and in vivo. Collectively, these results indicate a novel mechanism by which SCLC-derived exosomes induce immunosuppression of distant MØ to promote systemic metastasis by activating NLRP6. Here, we highlight the close relationship between the tumor-derived exosomes, inflammasomes and immune microenvironment in SCLC metastasis.
    DOI:  https://doi.org/10.1038/s41419-022-05336-0
  9. Adv Sci (Weinh). 2022 Oct 17. e2201609
    Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.
    Qiurong Yang, Jing Xu, Jianmei Gu, Hui Shi, Jiayin Zhang, Jianye Zhang, Zhe-Sheng Chen, Xinjian Fang, Taofeng Zhu, Xu Zhang.
      Extracellular vesicles (EVs) are cell-derived nanosized vesicles that mediate cell-to-cell communication via transporting bioactive molecules and thus are critically involved in various physiological and pathological conditions. EVs contribute to different aspects of cancer progression, such as cancer growth, angiogenesis, metastasis, immune evasion, and drug resistance. EVs induce the resistance of cancer cells to chemotherapy, radiotherapy, targeted therapy, antiangiogenesis therapy, and immunotherapy by transferring specific cargos that affect drug efflux and regulate signaling pathways associated with epithelial-mesenchymal transition, autophagy, metabolism, and cancer stemness. In addition, EVs modulate the reciprocal interaction between cancer cells and noncancer cells in the tumor microenvironment (TME) to develop therapy resistance. EVs are detectable in many biofluids of cancer patients, and thus are regarded as novel biomarkers for monitoring therapy response and predicting prognosis. Moreover, EVs are suggested as promising targets and engineered as nanovehicles to deliver drugs for overcoming drug resistance in cancer therapy. In this review, the biological roles of EVs and their mechanisms of action in cancer drug resistance are summarized. The preclinical studies on using EVs in monitoring and overcoming cancer drug resistance are also discussed.
    Keywords:  cancer therapy; drug delivery; drug resistance; extracellular vesicles; nanomedicine
    DOI:  https://doi.org/10.1002/advs.202201609
  10. Life Sci. 2022 Oct 18. pii: S0024-3205(22)00803-7. [Epub ahead of print] 121103
    The role of exosomes in the molecular mechanisms of metastasis: Focusing on EMT and cancer stem cells.
    Ghader Babaei, Mehdi Asghari Vostakolaei, Masumeh Rajabi Bazl, Shiva Gholizadeh-Ghaleh Aziz, Elham Gholipour, Kazem Nejati-Koshki.
      Exosomes are cell-derived small membrane-encapsulated vesicles that transfer biomolecules to surrounding cells. Exosomes play fundamental roles in cell-cell communications. They can also aggravate cancer progression and metastasis. Metastasis is a complicated and multi-serial process that is regulated by various mechanisms. Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are important participants in cancer metastasis. Recent studies demonstrate that exosomes are associated with metastasis by modulating the EMT and the function of CSCs. Accumulating evidence shows that exosomes are implicated in regulating tumor cell metastasis by modulating signaling pathways involved in EMT and CSCs. This review aims to discuss the effect of exosomes on signaling pathways associated with EMT and CSCs, as well as possible therapeutic strategies of exosomes in cancer metastasis.
    Keywords:  Cancer stem cells; EMT; Exosomes; Metastasis
    DOI:  https://doi.org/10.1016/j.lfs.2022.121103
  11. Clin Transl Oncol. 2022 Oct 20.
    The diagnostic role and mechanistic functions of exosomal lncRNAs in prostate cancer.
    Hangsheng Zhou, Hongyuan Wan, Yanyan Feng, Lijie Zhu, Yuanyuan Mi.
      Exosomes are small membrane-enclosed vesicles that are released by most living cells and harbor a diverse array of proteins, nucleic acids, and lipid cargos. These exosomes offer valuable biomarkers that may offer insights regarding as a range of physiological and pathological processes, including immune responses, cancer development, pregnancy, and diseases of the central nervous system. With the development of high-throughput technologies, the vital functions of long non-coding RNAs (lncRNAs) have been gradually entered people's vision and become new research hotspots. Nowadays, lncRNAs can play important roles in cancer progression by combining with miRNAs, activating molecular targets and other ways, and are also related to the diagnosis, treatment and prognosis for cancer, such as prostate cancer. Current review focused on the summary of diagnostic roles and mechanistic functions about exosomal lncRNAs in prostate cancer.
    Keywords:  Biomarker; Exosomes; Function; Prostate cancer; lncRNA
    DOI:  https://doi.org/10.1007/s12094-022-02982-w
  12. Head Neck. 2022 Oct 22.
    Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection.
    Chenna R Galiveti, Damaris Kuhnell, Jacek Biesiada, Xiang Zhang, Karl T Kelsey, Vinita Takiar, Alice L Tang, Trisha M Wise-Draper, Mario Medvedovic, Susan Kasper, Scott M Langevin.
       BACKGROUND: The objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection.
    METHODS: This study employed a combination of cell culture and case-control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation. miRNA-sequencing was performed on each sEV isolate.
    RESULTS: There were clear exo-miRNA profiles that distinguished HNSCC cell lines from nonpathologic oral epithelial control cells. While there was some overlap among profiles across all samples, there were apparent differences in exo-miRNA profiles according to HPV-status. Importantly, differential exo-miRNA profiles were also apparent in serum from early-stage HNSCC cases relative to cancer-free controls.
    CONCLUSIONS: Our findings indicate that exo-miRNA are highly dysregulated in HNSCC and support the potential of exo-miRNA as biomarkers for HNSCC.
    Keywords:  HNSCC; HPV; exosomes; head and neck cancer; miRNA
    DOI:  https://doi.org/10.1002/hed.27231
  13. Cancer Biol Ther. 2022 Dec 31. 23(1): 1-14
    Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer.
    Chuangui Li, Zhen Sun, Yajun Song, Yong Zhang.
      Application of bone marrow-derived mesenchymal stem cell-derived exosomes (BMSC-exos) in cancer treatment has been widely studied. Here, we elaborated the function of BMSC-exos containing microRNA-187 (miR-187) in prostate cancer. Differentially expressed miRs and genes were screened with microarray analysis. The relationship between CD276 and miR-187 in prostate cancer was evaluated. Following miR-187 mimic/inhibitor or CD276 overexpression transfection, their actions in prostate cancer cell biological processes were analyzed. Prostate cancer cells were then exposed to BMSC-exos that were treated with either miR-187 mimic/inhibitor or CD276 overexpression for pinpointing the in vitro and in vivo effects of exosomal miR-187. miR-187 was poorly expressed while CD276 was significantly upregulated in prostate cancer. Additionally, restoring miR-187 inhibited the prostate cancer cell malignant properties by targeting CD276. Upregulation of miR-187 led to declines in CD276 expression and the JAK3-STAT3-Slug signaling pathway. Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.
    Keywords:  CD276; JAK3-STAT3-Slug signaling pathway; Prostate cancer; exosomes; human bone marrow-derived mesenchymal stem cells; microRNA-187
    DOI:  https://doi.org/10.1080/15384047.2022.2123675
  14. Int J Gen Med. 2022 ;15 7831-7842
    Identification of the Level of Exosomal Protein by Parallel Reaction Monitoring Technology in HCC Patients.
    Hui Huang, Qiqi Zhang, Yong Zhang, Xueying Sun, Chunyan Liu, Qi Wang, Yushuang Huang, Qingwei Li, Zepan Wu, Chunwen Pu, Aijun Sun.
       Purpose: Reliable biomarkers for the diagnosis and differential diagnosis of various stages of liver cancer are lacking. In this study, we aim to detect the levels of differentially expressed proteins (DEPs) in serum exosomes of patients with different liver diseases using a sensitive method.
    Patients and Methods: Exosomes were purified and validated. The expression of DEPs in exosomes from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) was validated by parallel reaction monitoring (PRM) technology and Western blotting, and the biological functions were analyzed by bioinformatics analysis.
    Results: A total of 11 DEPs were identified by PRM technology. Significantly higher level of haptoglobin (Hp) was detected in HCC patients as compared to LC and CHB patients. HCC patients had a significantly lower level of transthyretin (TTR) in the patients with CHB. Among the patients with HCC who undertaken surgery, the postoperative levels of CRP, SERPINA3 and Heparin cofactor 2 (SERPIND1) were significantly reduced compared to their respective preoperative levels.
    Conclusion: Hp and TTR may be potential markers for early diagnosis of HCC. CRP, SERPINA3 and SERPIND1 may serve as potential prognostic indicators for HCC patients undertaken surgery.
    Keywords:  biomarker; exosome; hepatocellular carcinoma; mass spectrometry
    DOI:  https://doi.org/10.2147/IJGM.S384140
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