Chinese Journal of Cancer Research最新文献

{"title":"Identification of cancer patients using claims data from health insurance systems: A real-world comparative study","authors":"Hongrui Tian, Ruiping Xu, Feng-lei Li, Chuan-hai Guo, Lixin Zhang, Zhen Liu, Mengfei Liu, Yaqi Pan, Zhonghu He, Y. Ke","doi":"10.21147/j.issn.1000-9604.2019.04.13","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.13","url":null,"abstract":"Objective To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. Methods We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People’s Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. Results The sensitivity of NCMS was 95.2% (93.8%−96.3%) and 92.0% (88.3%−94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%−98.5%) in ACH and 89.0% (84.9%−92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P<0.01). Conclusions Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48244328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999−2017","authors":"R. Guo, J. Si, J. Xue, Yonghui Su, M. Mo, Benlong Yang, Qi Zhang, W. Chi, Y. Chi, Jiong Wu","doi":"10.21147/j.issn.1000-9604.2019.04.09","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.09","url":null,"abstract":"Objective Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time. Methods Females under 40 years of age diagnosed with breast cancer during the periods 1999−2017 and 1999−2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up. Results The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort (from 35.3% to 41.9%; P=0.008), whereas it decreased in SEER cohort (from 42.4% to 33.0%; P<0.0001). The percentage of estrogen receptor (ER)-positive cancers was consistently increased in both the invasive ductal carcinoma (IDC) and DCIS patients in the two cohorts. Breast-conserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period. Conclusions With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial de-escalation in surgical therapies in young breast cancer patients.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45973057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging","authors":"Chen Zhang, Xinyu Ling, Yanxiu Guo, C. Yuan, Hong-yan Cheng, X. Ye, R. Ma, Yinli Zhang, Yi Li, X. Chang, B. Kong, Tao Liu, H. Cui","doi":"10.21147/j.issn.1000-9604.2019.04.11","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.11","url":null,"abstract":"Objective To evaluate the imaging potential of a novel near-infrared (NIR) probe conjugated to COC183B2 monoclonal antibodies (MAb) in ovarian cancer (OC). Methods The expression of OC183B2 antigen in OC was determined by immunohistochemical (IHC) staining using tissue microarrays with the H-score system and immunofluorescence (IF) staining of tumor cell lines. Imaging probes with the NIR fluorescent dye cyanine 7 (Cy7) conjugated to COC183B2 Mab were chemically engineered. OC183B2-positive human OC cells (SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging (BLI) was performed to detect tumor location and growth. COC183B2-Cy7 at 1.1, 3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline (PBS), free Cy7 dye and mouse isotype immunoglobulin G (IgG)-Cy7 (delivered at the same doses as COC183B2-Cy7) were used as controls. Results The expression of OC183B2 with a high H-score was more prevalent in OC tissue than fallopian tube (FT) tissue. Among 417 OC patients, the expression of OC183B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background (T/B) ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h post-injection (hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183B2 positive. Conclusions COC183B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42539395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 18FDG PET/CT-based volume parameter is a predictor of overall survival in patients with local advanced gastric cancer","authors":"Jinling Song, Zhongwu Li, Puyun Chen, Jiangyuan Yu, Feng Wang, Zhi Yang, Xue-juan Wang","doi":"10.21147/j.issn.1000-9604.2019.04.07","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.07","url":null,"abstract":"Objective The present study investigated the prognosis value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced gastric cancer (LAGC). Methods In total, 144 patients [median age 63 (range: 48−80) years old] with LAGC underwent18F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were measured on PET/CT and correlated with clinicopathological features and survival. Results Significant differences in SUVmean, SUVmax, MTV and TLG were found according to Lauren’s classification, histologic grade and T category (P<0.05). During the 26.5-month follow-up, 51 (35.4%) patients died and 70 (48.6%) exhibited disease progression. The optimal thresholds of MTV and TLG were 15.1 cm3 and 47.3 cm3, respectively. The 3-year progression-free survival (PFS) and overall survival (OS) for patients with high TLG values were 30% and 38% compared to 38% and 47% for low TLG values, respectively (P<0.05). Univariate and multifactor analyses demonstrated that lymph node metastasis and T stage were independent prognostic factors for PFS; T stage, histologic grade and TLG were independent prognostic factors for OS (P<0.05). Molecular markers had no relationship with patient’s outcomes. Conclusions Metabolic activity of primary gastric tumors from 18F-FDG PET/CT is a prognostic factor in patients with LAGC.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44532413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy","authors":"S. Seo, M. Ryu, B. Ryoo, Yangsoon Park, Y. S. Park, Y. Na, Chae-Won Lee, Ju-kyung Lee, Yoon-Koo Kang","doi":"10.21147/j.issn.1000-9604.2019.04.06","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.06","url":null,"abstract":"Objective To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting. Methods MET amplification was assessed using fluorescence in situ hybridization (FISH) in 50 patients and quantitative polymerase chain reaction (qPCR) in 326 patients; 259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis. Results The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5 (κ=0.778, P<0.001). Twenty-one out of 326 patients (6.4%) were identified asMET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≥2 (33.3% vs. 10.5% P=0.007), peritoneal metastasis (76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels (28.6% vs. 7.3%, P=0.006). The median overall survival (OS) and progression-free survival (PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio (HR)=0.68, 95% confidence interval (95% CI): 0.35−1.32, P=0.254 for PFS; HR=0.68, 95% CI: 0.35−1.32, P=0.251 for OS]. Conclusions qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47193548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAT1, a direct transcriptional target of E2F1, suppresses cell proliferation, migration and invasion in esophageal squamous cell carcinoma","authors":"Yu Wang, Guangchao Wang, Yunping Ma, Jinglei Teng, Yan Wang, Yongping Cui, Yan Dong, S. Shao, Q. Zhan, Xuefeng Liu","doi":"10.21147/j.issn.1000-9604.2019.04.05","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.05","url":null,"abstract":"Objective Growing evidence indicates that FAT atypical cadherin 1 (FAT1) has aberrant genetic alterations and exhibits potential tumor suppressive function in esophageal squamous cell carcinoma (ESCC). However, the role of FAT1 in ESCC tumorigenesis remains not well elucidated. The aim of this study was to further investigate genetic alterations and biological functions of FAT1, as well as to explore its transcriptional regulation and downstream targets in ESCC. Methods The mutations of FAT1 in ESCC were achieved by analyzing a combined study from seven published genomic data, while the copy number variants of FAT1 were obtained from an analysis of our previous data as well as of The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases using the cBioPortal. The transcriptional regulation of FAT1 expression was investigated by chromatin immunoprecipitation (ChIP) and the luciferase reporter assays. In-cell western, Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to assess the indicated gene expression. In addition, colony formation and Transwell migration/invasion assays were employed to test cell proliferation, migration and invasion. Finally, RNA sequencing was used to study the transcriptomes. Results FAT1 was frequently mutated in ESCC and was deleted in multiple cancers. Furthermore, the transcription factor E2F1 occupied the promoter region of FAT1, and depletion of E2F1 led to a decrease in transcription activity and mRNA levels of FAT1. Moreover, we found that knockdown of FAT1 promoted KYSE30 and KYSE150 cell proliferation, migration and invasion; while overexpression of FAT1 inhibited KYSE30 and KYSE410 cell proliferation, migration and invasion. In addition, knockdown of FAT1 led to enrichment of the mitogen-activated protein kinase (MAPK) signaling pathway and cell adhesion process. Conclusions Our data provided evidence for the tumor suppressive function of FAT1 in ESCC cells and elucidated the transcriptional regulation of FAT1 by E2F1, which may facilitate the understanding of molecular mechanisms of the progression of ESCC.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44623762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomics-based predictive risk score: A scoring system for preoperatively predicting risk of lymph node metastasis in patients with resectable non-small cell lung cancer","authors":"Lan He, Yanqi Huang, Lixu Yan, Jun-hui Zheng, C. Liang, Zaiyi Liu","doi":"10.21147/j.issn.1000-9604.2019.04.08","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.08","url":null,"abstract":"Objective To develop and validate a radiomics-based predictive risk score (RPRS) for preoperative prediction of lymph node (LN) metastasis in patients with resectable non-small cell lung cancer (NSCLC). Methods We retrospectively analyzed 717 who underwent surgical resection for primary NSCLC with systematic mediastinal lymphadenectomy from October 2007 to July 2016. By using the method of radiomics analysis, 591 computed tomography (CT)-based radiomics features were extracted, and the radiomics-based classifier was constructed. Then, using multivariable logistic regression analysis, a weighted score RPRS was derived to identify LN metastasis. Apparent prediction performance of RPRS was assessed with its calibration, discrimination, and clinical usefulness. Results The radiomics-based classifier was constructed, which consisted of 13 selected radiomics features. Multivariate models demonstrated that radiomics-based classifier, age group, tumor diameter, tumor location, and CT-based LN status were independent predictors. When we assigned the corresponding score to each variable, patients with RPRSs of 0−3, 4−5, 6, 7−8, and 9 had distinctly very low (0%−20%), low (21%−40%), intermediate (41%−60%), high (61%−80%), and very high (81%−100%) risks of LN involvement, respectively. The developed RPRS showed good discrimination and satisfactory calibration [C-index: 0.785, 95% confidence interval (95% CI): 0.780−0.790]. Additionally, RPRS outperformed the clinicopathologic-based characteristics model with net reclassification index (NRI) of 0.711 (95% CI: 0.555−0.867). Conclusions The novel clinical scoring system developed as RPRS can serve as an easy-to-use tool to facilitate the preoperatively individualized prediction of LN metastasis in patients with resectable NSCLC. This stratification of patients according to their LN status may provide a basis for individualized treatment.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49130362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese guidelines for diagnosis and treatment of melanoma 2018 (English version)","authors":"National Health Commission of PRC","doi":"10.21147/j.issn.1000-9604.2019.04.02","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.04.02","url":null,"abstract":"1. Overview 2. Screening and diagnosis 2.1 Surveillance and screening of high-risk population 2.2 Diagnosis of melanoma 2.2.1 Clinical symptoms 2.2.2 Imaging diagnosis 2.2.3 Laboratory tests 2.2.4 Focus biopsy 2.3 Pathological diagnosis of melanoma 2.3.1 Criteria for pathological diagnosis 2.3.2 Standard pathological diagnosis of melanoma 2.3.3 Pathological report of melanoma 2.4 Clinical diagnostic criteria and route map of melanoma 3. Staging 4. Treatment 4.1 Surgical treatment 4.1.1 Wide excision 4.1.2 Sentinel lymph node biopsy (SLNB) 4.1.3 Lymph node dissection 4.1.4 Treatment of local recurrence or local metastasis 4.1.5 Postoperative adjuvant therapy (prevention and treatment for metastasis and recurrence) 4.2 Radiotherapy 4.2.1 Adjuvant radiotherapy 4.2.2 Plaque radiotherapy 4.3 Systemic therapy 4.3.1 Systemic therapy and response evaluation criteria 4.3.2 Symptomatic supportive therapy 4.3.3 Therapy of special lesions","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41813372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant hormone therapy after radical prostatectomy in high-risk localized and locally advanced prostate cancer: First multicenter, observational study in China","authors":"D. Ye, Wei Zhang, Lulin Ma, C. Du, Liping Xie, Yiran Huang, Q. Wei, Z. Ye, Y. Na","doi":"10.21147/j.issn.1000-9604.2019.03.13","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.03.13","url":null,"abstract":"Objective Potential of combined androgen blockade (CAB) has not been explored extensively in Chinese males with prostate cancer (PCa). Therefore, this study evaluated the 2-year prostate-specific antigen (PSA) recurrence rate and quality of life (QoL) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy (HT) after radical prostatectomy (RP). Methods This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor (preoperative PSA>20 ng/mL or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice. Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up. Results A total of 189 patients (mean age: 66.9±6.5 years) were recruited, among which 112 (59.3%) patients showed serum PSA>20 ng/mL preoperatively. The highest postoperative pathological advancement noticed was from clinical T2 (cT2) to pathological T3 (pT3) (43.9%) stage. The majority of the patients (66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence (15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist (LHRHa) (16.1%), and antiandrogen (19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P QoL score of 119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months. Conclusions Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in high-risk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens (AA) or LHRHa therapy. Further long-term therapy (>12 months) significantly improved QoL compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving QoL.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47971673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutant p53 increases exosome-mediated transfer of miR-21-3p and miR-769-3p to promote pulmonary metastasis","authors":"Q. Ju, Lina Zhao, Jiajia Gao, Lanping Zhou, Yang Xu, Yulin Sun, Xiaohang Zhao","doi":"10.21147/j.issn.1000-9604.2019.03.15","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2019.03.15","url":null,"abstract":"Objective Tumor metastasis is a complex, multistep process that depends on tumor cells and their communication with the tumor microenvironment. A p53 gain-of-function mutant has been shown to enhance the tumorigenesis, invasion, and metastasis abilities of tumor cells. This study aimed to investigate the roles of p53 R273H mutation in the tumor microenvironment. Methods The in vitro and in vivo effects of the p53 R273H mutant on the invasion and metastasis of HCT116 cells were investigated. Exosomes from wild-type and HCT116-TP53(R273H) cells were cocultured with mouse embryonic fibroblasts (MEFs). The roles of differentially expressed exosomal microRNAs identified by microarray analysis were investigated. The functions of the p53 R273H mutant in tumor cells were also investigated via gene expression microarray and quantitative polymerase chain reaction (qPCR) analyses. Results Introducing p53 R273H mutant into HCT116 cells significantly potentiated pulmonary metastasis in vivo. In the presence of exosomes derived from HCT116-TP53(R273H) cells, the exosomes were taken up by MEFs and became activated. Microarray analysis showed that the p53 R273H mutation increased the exosomal levels of miR-21-3p and miR-769-3p. Intriguingly, in clinical samples, miR-21-3p and miR-769-3p levels were significantly higher in patients with a p53 mutation than in those without this mutation. Furthermore, both miR-21-3p and miR-769-3p activated fibroblasts and exerted a synergistic effect via their target genes on the transforming growth factor-β (TGF-β)/Smad signaling pathway. The activated fibroblasts excreted cytokine TGF-β and may have reciprocally induced cancer cells to undergo epithelial-mesenchymal transition (EMT). Indeed, HCT116-TP53(R273H) cells showed increased expression of ZEB1 and SNAI2 and decreased transcription of several cell adhesion molecules. Conclusions The mutant p53-exosomal miR-21-3p/miR-769-3p-fibroblast-cytokine circuit appears to be responsible for communication between tumor and stromal cells, with exosomal miRNAs acting as a bridge. miR-21-3p and miR-769-3p are potential predictive markers of pulmonary metastasis and candidate targets for therapeutic interventions.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43466710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}