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  • American Association for Cancer Research (AACR)  (166)
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  • 1
    Online Resource
    Online Resource
    The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Prevention Research Vol. 14, No. 5 ( 2021-05-01), p. 563-572
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 14, No. 5 ( 2021-05-01), p. 563-572
    Abstract: Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the development of numerous colorectal adenomas in young adults. Metformin, an oral diabetic drug, has been shown to have antineoplastic effects and a favorable safety profile. We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP. Thirty-four FAP patients were randomly assigned in a 1:2:2 ratio to receive placebo, 500 mg metformin, or 1,500 mg metformin per day orally for 7 months. The number and size of polyps and the global polyp burden were evaluated before and after the intervention. This study was terminated early based on the results of the interim analysis. No significant differences were determined in the percentage change of colorectal and duodenal polyp number over the course of treatment among the three treatment arms (P = 0.627 and P = 1.000, respectively). We found no significant differences in the percentage change of colorectal or duodenal polyp size among the three groups (P = 0.214 and P = 0.803, respectively). The overall polyp burdens of the colorectum and duodenum were not significantly changed by metformin treatment at either dosage. Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm. In conclusion, 7 months of treatment with 500 mg or 1,500 mg metformin did not reduce the mean number or size of polyps in the colorectum or duodenum in FAP patients (ClinicalTrials.gov ID: NCT01725490). Prevention Relevance: A 7-month metformin treatment (500 mg or 1,500 mg) did not reduce the number or size of polyps in the colorectum or duodenum of FAP patients as compared to placebo. These results do not support the use of metformin to promote regression of intestinal adenomas in FAP patients.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-20-0580
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2422346-3
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  • 2
    Online Resource
    Online Resource
    Hepatocellular Carcinoma Risk Steadily Persists over Time Despite Long-Term Antiviral Therapy for Hepatitis B: A Multicenter Study
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 29, No. 4 ( 2020-04-01), p. 832-837
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 4 ( 2020-04-01), p. 832-837
    Abstract: Long-term antiviral therapy (AVT) for chronic hepatitis B (CHB) reduces the risk of hepatocellular carcinoma (HCC). We assessed the temporal trends in the incidence of HCC over time during long-term AVT among Asian patients with CHB. Methods: Patients with CHB receiving entecavir/tenofovir (ETV/TDF) as a first-line antiviral were recruited from four academic hospitals in the Republic of Korea. We compared the incidence of HCC during and after the first 5 years of ETV/TDF treatment. Results: Among 3,156 patients, the median age was 49.6 years and males predominated (62.4%). During the follow-up, 9.0% developed HCC. The annual incidence of HCC per 100 person-years during the first 5 years (n = 1,671) and after the first 5 years (n = 1,485) was statistically similar (1.93% vs. 2.27%, P = 0.347). When the study population was stratified according to HCC prediction model, that is, modified PAGE-B score, the annual incidence of HCC was 0.11% versus 0.39% in the low-risk group ( & lt;8 points), 1.26% versus 1.82% in the intermediate-risk group (9–12 points), and 4.63% versus 5.24% in the high-risk group (≥13 points; all P & gt; 0.05). A Poisson regression analysis indicated that the duration of AVT did not significantly affect the overall trend of the incidence of HCC (adjusted annual incidence rate ratio = 0.85; 95% confidence interval, 0.66–1.11; P = 0.232). Conclusions: Despite long-term AVT, the risk of HCC steadily persists over time among patients with CHB in the Republic of Korea, in whom HBV genotype C2 predominates. Impact: Careful HCC surveillance is still essential.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-19-0614
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 3
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    The Relationship Between Breast Density Change During Menopause and the Risk of Breast Cancer in Korean Women
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Prevention Research Vol. 14, No. 12 ( 2021-12-01), p. 1119-1128
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 14, No. 12 ( 2021-12-01), p. 1119-1128
    Abstract: The aim of this study was to investigate the relationship between changes in breast density during menopause and breast cancer risk. Methods: This study was a retrospective, longitudinal cohort study for women over 30 years of age who had undergone breast mammography serially at baseline and postmenopause during regular health checkups at Samsung Medical Center. None of the participants had been diagnosed with breast cancer at baseline. Mammographic breast density was measured using the American College of Radiology Breast Imaging Reporting and Data System. Results: During 18,615 person-years of follow-up (median follow-up 4.8 years; interquartile range 2.8–7.5 years), 45 participants were diagnosed with breast cancer. The prevalence of dense breasts was higher in those who were younger, underweight, had low parity or using contraceptives. The cumulative incidence of breast cancer increased 4 years after menopause in participants, and the consistently extremely dense group had a significantly higher cumulative incidence (CI) of breast cancer compared with other groups [CI of extremely dense vs. others (incidence rate per 100,000 person-years): 375 vs. 203, P & lt; 0.01]. Conclusion: Korean women whose breast density was extremely dense before menopause and who maintained this density after menopause were at two-fold greater risk of breast cancer. Prevention Relevance: Extremely dense breast density that is maintained persistently from premenopause to postmenopause increases risk of breast cancer two fold in Korean women. Therefore, women having risk factors should receive mammography frequently and if persistently extremely dense breast had been detected, additional modalities of BC screening could be considered.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-20-0542
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2422346-3
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  • 4
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    Abstract A005: Ultra-rapid and precise measurement of HER2 copy number alteration by next-generation digital PCR capable of real-time analysis in patients with breast cancer: A multicenter retrospective study
    American Association for Cancer Research (AACR) ; 2024
    In:  Cancer Research Vol. 84, No. 3_Supplement_1 ( 2024-02-01), p. A005-A005
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 84, No. 3_Supplement_1 ( 2024-02-01), p. A005-A005
    Abstract: The HER2 diagnostics is necessary for selection of patients harboring HER2 gene amplification or protein overexpression who will benefit from anti-HER2 therapies in breast cancer. However, HER2 testing is still challenging due to the subjective natures of immunohistochemistry (IHC) and in situ hybridization (ISH), standard methods for determining HER2 status. Thus, a new method is needed to accurately quantify HER2 levels. Here, we developed a clinically reliable HER2 testing method enabling ultra-fast detection of HER2 gene amplification with high accuracy by using the digital real-time PCR (drPCR) system, a potential new diagnostic platform with improved performance by integrating both real-time and digital PCR technologies. For drPCR-based HER2 copy number (CN) measurement, primer-probe sets specific to HER2 gene and a genomic region adjacent to chromosome 17 centromere (CEP17) were designed, and the optimal drPCR condition was determined in clinical breast tumor specimens. To test the clinical validity and standardize procedures of drPCR-based HER2 status evaluation, three independent breast cancer cohorts from different institutions were enrolled, which assigned as a training (SCHU hospital, n = 103) and two validation sets (SNU hospital, n = 170; CNUH hospital, n = 45), and the drPCR assay was compared with current standard HER2 testing methods. In the training cohort, the HER2/CEP17 ratio values from FISH and drPCR tests were highly correlated (r2 = 0.81; P & lt; 0.001), and the drPCR results displayed 98.1% concordance to HER2 status defined by IHC and/or FISH with 92.6% sensitivity and 100% specificity. Eight samples further verified by targeted NGS showed 100% concordance of dPCR to NGS. Consistently, two validation cohorts also showed high concordance of drPCR to IHC and/or ISH results (accuracy = 97.1% and 97.8% in SNU and CNUH cohorts, respectively). The optimal cutoff for HER2 positivity in the drPCR assay was set as a HER2/CEP17 ratio ≥ 1.9 with AUC of 0.963 based on the results from training cohort, and the same cut-off for drPCR was applicable to two independent validation cohorts, supporting the clinical validity of our drPCR-based HER2 assessment. In some discordant cases, low tumor purity (≤ 25%) was observed and microdissection partly improved the drPCR results. The discordance between drPCR and ISH results was also found in marginal HER2+ cases with HER2/CEP17 ratio 2-3, but these cases showed inter-observer variability when re-evaluating the ISH/IHC data due to intratumoral HER2 heterogeneity. Of note, in HER2 IHC3+ cases with negative drPCR results, re-evaluation of IHC using an artificial intelligence (AI)-based HER2 scoring system revised the HER2 IHC 3+ score to 2+, and ISH assessment also confirmed that these cases are indeed HER2-negative, proving the high accuracy of HER2 CN drPCR assay. In conclusion, given the advantages of drPCR-based HER2 assessment with high accuracy, sensitivity, and simplicity, the drPCR assay could be a complementary or alternative method to IHC and ISH to greatly improve current HER2 testing. Citation Format: Jin hyuk Chang, YoonSik Kim, Hee-Joo Choi, Soo Young Park, Ji-Hye Park, Hee-Young Won, Min Ji Song, Da Sol Kim, Hayeon Kim, Sohyeon Yang, Nam Hun Heo, Minsik Song, Seung-Shick Shin, Do Young Lee, Han Suk Ryu, Si-Hyong Jang, Jeong-Yeon Lee. Ultra-rapid and precise measurement of HER2 copy number alteration by next-generation digital PCR capable of real-time analysis in patients with breast cancer: A multicenter retrospective study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A005.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.ADVBC23-A005
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2024
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    detail.hit.zdb_id: 1432-1
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  • 5
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    Abstract 404: Proinflammatory cytokine IL-1β stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 404-404
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 404-404
    Abstract: Recent studies have suggested that mast cells have critical roles in angiogenesis. However, the detailed mechanism by which mast cells contribute to angiogenesis is not yet clearly understood, especially in response to proinflammatory cytokines. In this study, we showed that the proinflammatory cytokine IL-1β induces the synthesis of IL-8, a potent angiogenic factor, in human mast cells via the leukotriene B4 receptor (BLT)2. We also characterized the BLT2 downstream signaling pathway and determined that BLT2-mediated IL-8 synthesis involves the upregulation of Nox1, a member of the NADPH oxidase family, Nox1-dependent reactive oxygen species generation and the subsequent activation of the redox-sensitive transcription factor NF-κB. For instance, knockdown of BLT2 and Nox1 with specific small interfering RNA, treatment with a specific BLT2 antagonist, LY255283, or treatment with a potential Nox inhibitor, diphenylene iodonium, suppressed IL-1β-induced IL-8 synthesis. We found that the conditioned media collected from IL-1β-treated human mast cell line HMC-1 had significantly enhanced angiogenic activity that could be dramatically attenuated by either small interfering RNA knockdown of BLT2 or treatment with neutralizing Ab to IL-8. Finally, the experiments were repeated using human primary cord blood-derived mast cells, and the results were clearly reproduced. Taken together, our results suggest that BLT2-Nox1-reactive oxygen species-dependent pathway plays a role in promoting the secretion of IL-8 from human mast cells in response to the proinflammatory cytokine IL-1β, thus contributing to angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 404. doi:10.1158/1538-7445.AM2011-404
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-404
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 6
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    A Phase II, Prospective, Randomized, Multicenter, Open-Label Study of GX-188E, an HPV DNA Vaccine, in Patients with Cervical Intraepithelial Neoplasia 3
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 7 ( 2020-04-01), p. 1616-1623
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 7 ( 2020-04-01), p. 1616-1623
    Abstract: To determine the efficacy of the therapeutic DNA vaccine GX-188E for inducing regression of cervical intraepithelial neoplasia (CIN) 3. Patients and Methods: We conducted a prospective, randomized, multicenter, open-label, phase II clinical trial of GX-188E in CIN3 patients positive for human papillomavirus (HPV) type 16/18. The primary endpoint was to determine the histopathologic regression to ≤CIN1 at visit seven (V7; 20 weeks after the first GX-188E injection), and an extension study was pursued until visit 8 (V8; 36 weeks after the first GX-188E injection). HPV-sequencing analysis and an ex vivo IFNγ ELISpot assay were performed using the collected cervical biopsy and blood samples from patients. Results: In total, 72 patients were enrolled and underwent randomization. Of them, 64 patients were included in per-protocol analysis (V7) and 52 in extension analysis (V8). Our data showed 52% (33/64) of patients at V7 and 67% (35/52) of patients at V8 presented histopathologic regression after receiving the GX-188E injection. We found that 73% (V7) and 77% (V8) of the patients with histologic regression showed HPV clearance. HPV clearance and histopathologic regression were significantly associated at V7 and at V8. Compared with the measurements at V1 (baseline), the patients at V8 with HPV clearance showed significantly higher fold changes in their IFNγ ELISpot responses compared with those without HPV clearance. The HPV sequence analysis revealed that the HPV type 16 E6/E7 variants D25E, V83L, and N29S were inversely associated with histopathologic regression at V8. Conclusions: GX-188E is an effective therapeutic vaccine against a cohort containing only CIN3 patients.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-1513
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 7
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    Abstract 2471: Clinical significance of noncoding circHIPK3 RNA in human hepatocellular carcinoma
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2471-2471
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2471-2471
    Abstract: Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with poor prognosis and high risk of recurrence. Previous studies have shown that various microRNAs (miRNAs) are frequently dysregulated in HCC, which contributes to cancer development and progression. Nonetheless, the regulation mechanism of miRNAs is still unclear. Circular noncoding RNA (circRNA) is highly conserved and stable covalently closed RNA circles with gene-regulatory potential. Recently, one abundant circRNA from HIPK3 gene, circHIPK3, has been identified, and its function has been elucidated as multiple miRNAs sponge. Thus, we aimed to investigate the clinical relevance of circHIPK3 in HCC. Materials and Methods: We analyzed clinical specimens from 152 pairs of HCC and corresponding normal liver (NL) tissues. Total RNAs were isolated from clinical tissues using Qiagen kit. CircHIPK3 expression levels were determined by quantitative real-time PCR (qRT-PCR), and its expression was normalized with GAPDH. In addition, we analyzed the correlation between circHIPK3 expression and various clinicopathologic features of HCC patients. Results: CircHIPK3 expression was significantly downregulated in HCC tissues compared to corresponding NL tissues (P=0.036). In HCC patients, circHIPK3 expression was strongly suppressed in more advanced tumors (P & lt;0.001). Further correlation analysis showed that circHIPK3 expression was significantly associated with T stage (P & lt;0.001), TNM stage (P & lt;0.001), BCLC stage (P & lt;0.001), and alpha-fetoprotein (AFP) expression (P=0.033). Conclusions: We have determined clinical significances of circHIPK3 expression in HCC, which may provide clinical evidence for the potential of circHIPK3 as novel markers for diagnosis and predicting prognosis in HCC patients. Citation Format: Gyeonghwa Kim, Jun Sik Yoon, Se Young Jang, Soo Young Park, Won Young Tak, Young-Oh Kweon, Keun Hur. Clinical significance of noncoding circHIPK3 RNA in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2471.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-2471
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    PPARδ Reprograms Glutamine Metabolism in Sorafenib-Resistant HCC
    American Association for Cancer Research (AACR) ; 2017
    In:  Molecular Cancer Research Vol. 15, No. 9 ( 2017-09-01), p. 1230-1242
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 9 ( 2017-09-01), p. 1230-1242
    Abstract: The tyrosine kinase inhibitor sorafenib is the only therapeutic agent approved for the treatment of advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is high. Here, we report metabolic reprogramming in sorafenib-resistant HCC and identify a regulatory molecule, peroxisome proliferator–activated receptor-δ (PPARδ), as a potential therapeutic target. Sorafenib-resistant HCC cells showed markedly higher glutamine metabolism and reductive glutamine carboxylation, which was accompanied by increased glucose-derived pentose phosphate pathway and glutamine-derived lipid biosynthetic pathways and resistance to oxidative stress. These glutamine-dependent metabolic alterations were attributed to PPARδ, which was upregulated in sorafenib-resistant HCC cells and human HCC tissues. Furthermore, PPARδ contributed to increased proliferative capacity and redox homeostasis in sorafenib-resistant HCC cells. Accordingly, inhibiting PPARδ activity reversed compensatory metabolic reprogramming in sorafenib-resistant HCC cells and sensitized them to sorafenib. Therefore, targeting compensatory metabolic reprogramming of glutamine metabolism in sorafenib-resistant HCC by inhibiting PPARδ constitutes a potential therapeutic strategy for overcoming sorafenib-resistance in HCC. Implications: This study provides novel insight into the mechanism underlying sorafenib resistance and a potential therapeutic strategy targeting PPARδ in advanced hepatocellular carcinoma. Mol Cancer Res; 15(9); 1230–42. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1541-7786.MCR-17-0061
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2097884-4
    SSG: 12
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  • 9
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    Abstract 3504: High expression of lncRNA-ATB and miR-21 as a biomarker in human hepatocellular carcinoma
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3504-3504
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3504-3504
    Abstract: Non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have emerged as novel gene-regulators. The aim of this study was to determine the clinical relevancies of 2 lncRNAs (lncRNA-ATB and MEG3) and 2 miRNAs (miR-21 and miR-31) in hepatocellular carcinoma (HCC). We analyzed clinical specimens from 100 pairs of HCC and matched normal liver (NL) tissues. MiRNAs and lncRNAs expression levels were evaluated by quantitative real-time PCR. In addition, we determined the clinical significance of the ncRNAs expression in matching tissue and serum exosome samples from HCC patients. MiR-21 significantly increased in HCC (P & lt;0.01) compared to corresponding NL tissues. LncRNA-ATB was significantly up-regulated in HCC (P & lt;0.05); however, lncRNA-MEG3 was down-regulated in HCC (P & lt;0.05) tissues. In addition, expression of miR-21 and lncRNA-ATB was significantly associated with the tumor size and poor prognosis of HCC patients. More importantly, expression of serum exosomal lncRNA-ATB and miR-21 was more significantly associated with HCC progression and poor patients survival compared to its’ tissue expression. We conclude that non-coding RNAs (lncRNA-ATB and miR-21) expression has the potential to serve as biomarkers for prognosis and targeted therapy in HCC patients. Citation Format: Eunhye Lee, Gyeonghwa Kim, Se Young Jang, Yong-Hun Choi, Yu Rim Lee, Won Young Tak, Young Oh Kweon, Soo Young Park, Keun Hur. High expression of lncRNA-ATB and miR-21 as a biomarker in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3504. doi:10.1158/1538-7445.AM2017-3504
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-3504
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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  • 10
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    Abstract 5441: Circulating exosomal microRNA-203 and microRNA-373 as non-invasive biomarkers for predicting prognosis and metastasis in human hepatocellular carcinoma
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5441-5441
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5441-5441
    Abstract: Background and Aim Hepatocellular carcinoma (HCC) is the fifth most common cancer and the most leading cause of cancer-related death worldwide. Although considerable progress has been made in treatment of HCC, early detection is still highly considered the key to improved survival. Thus, for the earlier diagnosis and accurate prediction of HCC, identification of non-invasive molecular biomarkers for HCC patients is an imperative need. Recently, cancer cell-derived extracellular vesicles (EVs) have been known to contain various intracellular biomolecules including microRNAs (miRNAs). The aim of this study was to evaluate whether exosomal miRNAs can serve as a serum-based biomarker in HCC. Materials and Methods We isolated exosome from serum samples from HCC patients as well as normal healthy controls using ultracentrifugation, and it was confirmed by expression of exosome markers (CD9, CD63, ALIX, and TSG101) based on immunoblotting. Next, the expression of 6 miRNAs (miRNA-24, -130a, -182, -203, -373, and -423) was analyzed in the exosome samples. We also investigated expression status of the 6 miRNAs in matched HCC tissues and corresponding normal liver tissues. MiRNAs expression was determined by quantitative real-time PCR (qRT-PCR), and miRNAs expression was normalized relative to cel-miR-39 and RNU6B expression for serum and tissue samples, respectively. Results We successfully purified exosome from serum clinical samples and detected miRNAs in the exosome. We observed that a subset of miRNAs from serum exosome, including miRNA-24, -130a, -182, -203, and -373 were enhanced in HCC patients than normal healthy controls. In further comparison between early stage and advanced stage of HCC patients, serum exosomal miRNA-203 (P & lt;0.05) and miRNA-373 (P & lt;0.05) were significantly up-regulated in advanced HCC patients. While no significant changes in the expression of other serum exosomal miRNAs (miRNA-24, -130a, -182, and -423) according to HCC progression. More interestingly, high serum exosomal miRNA-203 and miRNA-373 was associated with HCC progression (P & lt;0.01) as well as prognosis (P & lt;0.05) of HCC patients. Conclusions We provided the novel evidence for usefulness of serum circulating exosomal miR-203 and miR-373 expressions as strong potential biomarkers for predicting prognosis and metastasis of HCC patients. Citation Format: Gyeonghwa Kim, Eunhye Lee, Se Young Jang, Won Young Tak, Young Oh Kweon, Soo Young Park, Keun Hur. Circulating exosomal microRNA-203 and microRNA-373 as non-invasive biomarkers for predicting prognosis and metastasis in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5441. doi:10.1158/1538-7445.AM2017-5441
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-5441
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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