scholarly journals CDKN2A Deletion Leading to Hematogenous Metastasis of Human Gastric Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Juanli Qiao ◽  
Yuan Tian ◽  
Xiaojing Cheng ◽  
Zhaojun Liu ◽  
Jing Zhou ◽  
...  

IntroductionSomatic copy number deletion (SCND) of CDKN2A gene is the most frequent event in cancer genomes. Whether CDKN2A SCND drives human cancer metastasis is far from clear. Hematogenous metastasis is the main reason of human gastric carcinoma (GC) death. Thus, prediction GC metastasis is eagerly awaited.MethodGC patients (n=408) enrolled in both a cross-sectional and a prospective cohorts were analysed. CDKN2A SCND was detected with a quantitative PCR assay (P16-Light). Association of CDKN2A SCND and GC metastasis was evaluated. Effect of CDKN2A SCND by CRISPR/Cas9 on biological behaviors of cancer cells was also studied.ResultsCDKN2A SCND was detected in 38.9% of GCs from patients (n=234) enrolled in the cross-sectional cohort. Association analysis showed that more CDKN2A SCND was recognized in GCs with hematogenous metastasis than those without (66.7% vs. 35.7%, p=0.014). CDKN2A SCND was detected in 36.8% of baseline pN0M0 GCs from patients (n=174) enrolled in the prospective study, the relationship between CDKN2A SCND and hematogenous metastasis throughout the follow-up period (62.7 months in median) was also significant (66.7% vs. 34.6%, p=0.016). Using CDKN2A SCND as a biomarker for predicting hematogenous metastasis of GCs, the prediction sensitivity and specificity were 66.7% and 65.4%. The results of functional experiments indicated that CDKN2A SCND could obviously downregulate P53 expression that consequently inhibited the apoptosis of MGC803 GC and HEK293T cells. This may account for hematogenous metastasis of GCs by CDKN2A SCND.ConclusionCDKN2A SCND may drive GC metastasis and could be used as a predictor for hematogenous metastasis of GCs.

2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9


1998 ◽  
Vol 124 (7) ◽  
pp. 383-388 ◽  
Author(s):  
Shohei Koyama ◽  
Tsunehiko Maruyama ◽  
Shinya Adachi ◽  
Mutsumi Nozue

Author(s):  
Peixin Dong ◽  
Ying Xiong ◽  
Yosuke Konno ◽  
Kei Ihira ◽  
Noriko Kobayashi ◽  
...  

Abstract Background Epithelial-to-mesenchymal transition (EMT) and aerobic glycolysis are fundamental processes implicated in cancer metastasis. Although increasing evidence demonstrates an association between EMT induction and enhanced aerobic glycolysis in human cancer, the mechanisms linking these two conditions in endometrial cancer (EC) cells remain poorly defined. Methods We characterized the role and molecular mechanism of the glycolytic enzyme hexokinase 2 (HK2) in mediating EMT and glycolysis and investigated how long noncoding RNA DLEU2 contributes to the stimulation of EMT and glycolysis via upregulation of HK2 expression. Results HK2 was highly expressed in EC tissues, and its expression was associated with poor overall survival. Overexpression of HK2 effectively promoted EMT phenotypes and enhanced aerobic glycolysis in EC cells via activating FAK and its downstream ERK1/2 signaling. Moreover, microRNA-455 (miR-455) served as a tumor suppressor by directly interacting with HK2 mRNA and inhibiting its expression. Furthermore, DLEU2 displayed a significantly higher expression in EC tissues, and increased DLEU2 expression was correlated with worse overall survival. DLEU2 acted as an upstream activator for HK2-induced EMT and glycolysis in EC cells through two distinct mechanisms: (i) DLEU2 induced HK2 expression by competitively binding with miR-455, and (ii) DLEU2 also interacted with EZH2 to silence a direct inhibitor of HK2, miR-181a. Conclusions This study identified DLEU2 as an upstream activator of HK2-driven EMT and glycolysis in EC cells and provided significant mechanistic insights for the potential treatment of EC.


Author(s):  
Efrén Murillo-Zamora ◽  
Oliver Mendoza-Cano ◽  
Benjamín Trujillo-Hernández ◽  
Xóchitl Trujillo ◽  
Miguel Huerta ◽  
...  

Background: We aimed to screen for depressive mood experienced during acute chikungunya (CHIKV) infection, and to evaluate the association of several exposures with the risk of depressive symptoms. Methods: A cross-sectional analysis of a multicenter cohort study took place and data from 354 adult individuals with confirmed CHIKV infection were analyzed. Participants were recruited in primary health care settings and the Patient Health Questionnaire-2 (PHQ-2) was used. Prevalence odds ratios (OR) and 95% confidence intervals (CIs) estimated by means of logistic models were used. Results: Depressive mood (PHQ-2 score 3 or higher) was reported by 44.1% of individuals. Subjects with articular effusion (OR = 3.37, 95% CI 1.77–8.11), gastrointestinal manifestations (diarrhea, vomiting or abdominal pain, OR = 1.97, 95 CI 1.21–3.19), and higher length of severe arthralgia (reference ≤ 14 days: 15–30 days, OR = 3.38, 95% CI 1.78–6.41; ≥ 30 days, OR = 1.69, 95% CI 0.95–3.01) were more likely to self-report depressive mood. Increasing age (≥ 40 years old, OR = 0.55, 95% CI 0.31–0.95) and rash (OR = 0.54, 95% CI 0.30–0.98) were associated with a decreased risk of depressive mood. Conclusions: Depressive mood seemed to be a frequent event among analyzed individuals, and markers associated with its risk were identified.


RADIOISOTOPES ◽  
1990 ◽  
Vol 39 (12) ◽  
pp. 565-568
Author(s):  
Xue Song CAO ◽  
Guang Yu YANG ◽  
Yin Chang ZHANG ◽  
Hiroshi KAWASAKI

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