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    Home > Active Ingredient News > Digestive System Information > Molecular Cancer Zhang Hao's team from Jinan University found that saliva-derived exosomal small RNAs can be used as biomarkers for the diagnosis and prognosis of esophageal cancer

    Molecular Cancer Zhang Hao's team from Jinan University found that saliva-derived exosomal small RNAs can be used as biomarkers for the diagnosis and prognosis of esophageal cancer

    • Last Update: 2022-02-22
    • Source: Internet
    • Author: User
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    iNaturetRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in response to various stresses commonly found in cancer
    .

    Recent studies have found that tsRNA is dysregulated in various types of cancer
    .

    However, exploration of the potential of tsRNA-based liquid biopsy is still in its early stages
    .

    Compared to ctDNA and CTCs, which require blood to obtain liquid biopsy samples, exosomes are present in almost all body fluids, such as blood, saliva, urine, and cerebrospinal fluid, broadening the choice of sources for liquid biopsy samples
    .

    On January 18, 2022, Zhang Hao's team from Jinan University published a research paper online entitled "A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study" at Molecular Cancer (IF=27).
    This study identified cancer-enriched small RNAs by RNA sequencing of salivary exosomes obtained from esophageal squamous cell carcinoma (ESCC) patients (n = 3) and healthy controls (n = 3).
    n = 66) for further verification
    .

    This study found that tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes from ESCC patients, ESCC tissues, and ESCC cells
    .

    A dual signature composed of these small RNAs was able to distinguish ESCC patients from controls with high sensitivity (90.
    50%) and specificity (94.
    20%)
    .

    Patients with high RSP had better overall survival (OS) (HR 4.
    95, 95%CI 2.
    90–8.
    46) and progression-free survival (PFS) (HR 3.
    69, 95%CI) than those with low RSP according to the prognostic bi-specific risk score (RSP).
    2.
    24–6.
    10) are all short
    .

    Furthermore, adjuvant therapy improved OS (HR 0.
    47, 95%CI 0.
    29-0.
    77) and PFS (HR 0.
    36, 95%CI 0.
    21-0.
    62) only in patients with high RSP
    .

    These findings are consistent across both training and validation cohorts
    .

    In conclusion, tsRNA-based signatures have not only diagnostic and prognostic potential, but also serve as preoperative biomarkers to select patients who will benefit from adjuvant therapy
    .

    Esophageal squamous cell carcinoma (ESCC) ranks seventh globally in cancer incidence and sixth in cancer mortality
    .

    Patients are usually in a predominant stage of lymph node metastasis at the time of diagnosis, which results in a 5-year survival rate of approximately 20%
    .

    Early detection and diagnosis of ESCC is expected to be important in order to maximize the chances of curative surgical resection
    .

    Currently, there is a lack of biomarkers suitable for the detection of early ESCC
    .

    In addition, 30% to 40% of patients experience local recurrence after surgical resection for curative purposes
    .

    Adjuvant radiotherapy and chemotherapy are important in ESCC, but their clinical benefit is controversial
    .

    There are also no biomarkers that predict the benefit of adjuvant therapy in ESCC
    .

    Therefore, for this malignancy, early detection of patients and more precise stratification to guide adjuvant therapy are urgently needed
    .

    Endoscopic biopsy biopsy is invasive and imaging studies are not sensitive as a screening modality for ESCC
    .

    Minimally invasive techniques such as cellular sponges or transnasal endoscopy have cost and discomfort barriers to widespread acceptance as screening methods for ESCC
    .

    Recently, liquid biopsy has been widely studied for non-invasive cancer detection, which is mainly based on three core biomaterials derived from cancer: circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes
    .

    Despite their potential, the use of ctDNA and CTCs as liquid biopsy methods has some limitations
    .

    Given that the proportion of ctDNA in total cell-free DNA is usually small, typically < 0.
    01%, detection sensitivity is a serious issue, especially for early cancer detection
    .

    Furthermore, translation of CTCs into clinical practice is limited by their isolation challenges due to their extreme rarity, fragility, and oncogenic/phenotypic heterogeneity
    .

    In contrast, exosomes are extracellular vesicles containing proteins, DNA and RNA that represent many of the characteristics of the cells that secrete them
    .

    Exosomes are secreted by various types of cells, reflecting the heterogeneous biological changes associated with tumors
    .

    Exosomes contain many types of small RNAs, such as miRNAs, piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), tRNA-derived small RNAs (tsRNAs), and other unidentified small RNAs
    .

    Although miRNAs are the most studied class of small RNA biomarkers in exosomes, other exosome-derived small RNAs are emerging as novel enriched diagnostic and prognostic biomarkers for cancer
    .

    tsRNAs (also known as tRNA-derived fragments (tRFs)) were originally thought to be degradation products, novel small noncoding RNAs (sncRNAs) generated from precursor or mature tRNAs
    .

    tsRNAs are produced in a nuclease (angiopoietin, RNY1, Dicer)-dependent manner in response to stresses such as amino acid starvation, oxidative stress, and hypoxia
    .

    Because the tumor microenvironment is characterized by hypoxia and nutrient deficiency, it is easy to confuse tsRNA with cancer
    .

    Recent studies have found that tsRNA is dysregulated in various types of cancer
    .

    However, exploration of the potential of tsRNA-based liquid biopsy is still in its early stages
    .

    Compared to ctDNA and CTCs, which require blood to obtain liquid biopsy samples, exosomes are present in almost all body fluids, such as blood, saliva, urine, and cerebrospinal fluid, broadening the choice of sources for liquid biopsy samples
    .

    Salivary exosome-based detection of chimeric RNA and mRNA as a non-invasive liquid biopsy method for diagnosing and monitoring disease progression
    .

    Identification of cancer-enriched sncRNAs in saliva exosomes from ESCC patients (figure from Molecular Cancer) RNA sequencing of salivary exosomes identified cancer-enriched small RNAs and further validated in the discovery cohort (n = 66)
    .

    This study found that tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes from ESCC patients, ESCC tissues, and ESCC cells
    .

    A dual signature composed of these small RNAs was able to distinguish ESCC patients from controls with high sensitivity (90.
    50%) and specificity (94.
    20%)
    .

    Patients with high RSP had better overall survival (OS) (HR 4.
    95, 95%CI 2.
    90–8.
    46) and progression-free survival (PFS) (HR 3.
    69, 95%CI) than those with low RSP according to the prognostic bi-specific risk score (RSP).
    2.
    24–6.
    10) are all short
    .

    Furthermore, adjuvant therapy improved OS (HR 0.
    47, 95%CI 0.
    29-0.
    77) and PFS (HR 0.
    36, 95%CI 0.
    21-0.
    62) only in patients with high RSP
    .

    These findings are consistent across both training and validation cohorts
    .

    In conclusion, tsRNA-based signatures have not only diagnostic and prognostic potential, but also serve as preoperative biomarkers to select patients who will benefit from adjuvant therapy
    .

    Reference message: https://molecular-cancer.
    biomedcentral.
    com/articles/10.
    1186/s12943-022-01499-8
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