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08 March 2020, Volume 47 Issue 3 Previous Issue    Next Issue

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Effect of miR-5581-5p/TRIM22 on acute promyelocytic leukemia cell differentiation Sun Wangnan, Du Pengchao, Qi Fu, Wang Wenfeng, Jiang Guosheng 2020, 47 (3):  129-134.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.001 Abstract ( 558 )   HTML ( 36 )   PDF (1715KB) ( 234 )   Save Objective To investigate the function of miR-5581-5p and its interaction with tripartite motif 22 (TRIM22) during the terminal differentiation of human acute promyelocytic leukemia (APL) cells into granulocytes. Methods APL cells (NB4) were differentiated into granulocytes by all-trans retinoic acid (ATRA), using dimethylsulfoxide (DMSO) as the control. The expression of TRIM22 was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting, and the expression of miR-5581-5p was detected by qRT-PCR during cell differentiation. miRNA expression was regulated by cell transfection with miR-5581-5p mimic and inhibitor, and negative control was set, and qRT-PCR was used to verify the regulatory effect. Luciferase binding assay was performed to detect the presence of targeted binding. Western blotting was used to detect the expression of TRIM22 after miRNA differential expression. Flow cytometry was used to detect the effects of the regulation of miR-5581-5p on the differentiation of NB4 cells induced by ATRA. Results After ATRA induced NB4 cells to differentiate into granulocytes, the gene expression level of TRIM22 was significantly higher than that of the control group (24.56±2.80 vs. 1.02±0.13; t=8.392, P=0.001). The level of protein expression was also significantly higher than that of the control group (0.80±0.01 vs. 0.17±0.01; t=44.900, P<0.001). The expression level of miR-5581-5p in NB4 cells differentiation group was significantly lower than that in the control group (0.14±0.02 vs. 1.01±0.08; t=10.840, P<0.001). The results of the dual luciferase reporter gene showed that the luciferase activity of the co-transfected miR-5581-5p mimic and TRIM22 WT group was significantly lower than that of the co-transfected miR-5581-5p mimic and TRIM22 MUT group (0.73±0.02 vs. 0.98±0.03; t=7.534, P=0.002). Western blotting showed that after transfection with miR-5581-5p inhibitor, the expression of TRIM22 was significantly higher than that of the negative control (0.44±0.01 vs. 0.21±0.01; t=18.290, P<0.001). While after transfection with miR-5581-5p mimic, the expression of TRIM22 decreased significantly compared with the negative control (0.62±0.01 vs. 0.80±0.02; t=6.402, P=0.003). CD11b expression of miR-5581-5p mimic group after ATRA treatment was significantly lower than that of the control group (45.80±1.80 vs. 56.61±1.88; t=4.159, P=0.014). The expression of CD11b in miR-5581-5p inhibitor group was significantly higher than that in the control group (66.48±2.54 vs. 52.60±1.70; t=4.539, P=0.011). Conclusion miRNA-5581-5p can bind to TRIM22 3'UTR and negatively regulate TRIM22 expression. The decrease of miR-5581-5p can increase the expression of TRIM22, then promote the differentiation of ATRA-induced NB4 cells into granulocytes. Figures and Tables | References | Related Articles | Metrics

Expressions of SPNS2 and Lgr5 in laryngeal squamous cell carcinoma and their correlations with prognosis Wang Xiaojun, Cao Peng, Zhu Xinhua 2020, 47 (3):  135-140.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.002 Abstract ( 602 )   HTML ( 20 )   PDF (1642KB) ( 260 )   Save Objective To investigate the expressions of sphingosine-1-phosphate transporter 2 (SPNS2) and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in laryngeal squamous cell carcinoma and their correlations with clinicopathological features and prognosis. Methods A total of 82 cases of squamous cell carcinoma were collected from the paraffin-embedded specimens of laryngeal cancer in Taixing People's Hospital of Jiangsu Province from March 2012 to March 2016. The expressions of SPNS2 and Lgr5 were detected by immunohistochemistry in 82 cancerous tissues and 50 adjacent normal tissues. The relationships between the expressions of SPNS2 and Lgr5 in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis were analyzed. Results The high expression rate of SPNS2 in laryngeal squamous cell carcinoma tissues was 40.24% (33/82), which was higher than 8.00% (4/50) in normal tissues adjacent to cancer. The high expression rate of Lgr5 in cancerous tissues was 46.34% (38/82), which was higher than 12.00% (6/50) in normal tissues adjacent to cancer. The differences were statistically significant (χ 2=16.008, P<0.001; χ 2=16.484, P<0.001). The expression status of SPNS2 was related to tumor size (χ 2=5.713, P=0.017), tumor stage (χ 2=7.071, P=0.008), tumor differentiation degree (χ 2=5.722, P=0.017) and lymph node metastasis (χ 2=6.595, P=0.010). There were significant differences in the expression status of Lgr5 in different tumor stage (χ 2=8.200, P=0.004), tumor differentiation (χ 2=9.435, P=0.002) and lymph node metastasis (χ 2=16.188, P<0.001). The 3-year overall survival rate of patients in SPNS2 low expression group was 90.91%, which was higher than that of patients in SPNS2 high expression group (71.43%, χ 2=4.975, P=0.026). The 3-year progression-free survival rate of patients in SPNS2 low expression group was 78.79%, which was higher than that of patients in SPNS2 high expression group (55.10%, χ 2=6.113, P=0.013). The 3-year overall survival rate of patients in Lgr5 low expression group was 86.84%, which was higher than that of patients in Lgr5 high expression group (65.91%, χ 2=5.801, P=0.016). The 3-year progression-free survival rate of patients in Lgr5 low expression group was 78.95%, which was higher than that of patients in Lgr5 high expression group (56.82%, χ 2=6.316, P=0.012). Multivariate Cox regression analysis showed that differentiation (RR=0.199, 95%CI: 0.057-0.691, P=0.011), tumor staging (RR=0.167, 95%CI: 0.053-0.531, P=0.002), SPNS2 (RR=0.208, 95%CI: 0.072-0.604, P=0.004) and Lgr5 (RR=0.198, 95%CI: 0.060-0.655, P=0.008) were risk factors for the prognosis of patients with laryngeal squamous cell carcinoma. Contingency correlation analysis showed a positive correlation between SPNS2 and Lgr5 expressions in laryngeal squamous cell carcinoma (C=0.591, P<0.001). Conclusion SPNS2 and Lgr5 are highly expressed in laryngeal squamous cell carcinoma and are closely related to clinicopathological features. And SPNS2 and Lgr5 are risk factors for the prognosis of patients with laryngeal squamous cell carcinoma. Figures and Tables | References | Related Articles | Metrics

Clinical observation of prophylactic use of pegylated recombinant human granulocyte stimulating factor in breast cancer patients with postoperative radiotherapy Du Yanfang, Fan Yanling, Hu Bing, Sun Lei, Liu Yuanjian, Li Baosheng, Huang Wei 2020, 47 (3):  141-145.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.003 Abstract ( 995 )   HTML ( 14 )   PDF (659KB) ( 276 )   Save Objective To investigate the efficacy and adverse effects of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia in patients undergoing sequential adjuvant radiotherapy after postoperative chemotherapy for breast cancer. Methods A total of 43 female patients with breast cancer from January 2017 to January 2019 in Shandong Cancer Hospital and Institute were analyzed prospectively. Twenty-one patients in the experimental group were given 6 mg of PEG-rhG-CSF subcutaneously 1-3 days before radiotherapy. In the control group, 22 patients were enrolled without PEG-rhG-CSF utilization. The lowest absolute neutrophil count (ANC), the number of days of radiotherapy interruption due to neutropenia, the number of recombinant human granulocyte colony-stimulating factor (rhG-CSF) used during radiotherapy and the occurrence of drug-induced skeletal muscle pain in the two groups were statistically analyzed. Results No neutropenia fever was observed in the two groups during radiotherapy. In the experimental group, there was no case of grade Ⅲ neutropenia; while in the control group, there were 3 cases of grade Ⅲ neutropenia. The median value of the lowest ANC in the experimental group was 1.56×10 9/L, higher than that in the control group (1.37×10 9/L), with a statistically significant difference (Z=-2.261, P=0.023). The median number of rhG-CSF used in the experimental group was 1, which was smaller than 2 in the control group, and the difference was statistically significant (Z=-2.498, P=0.012). The median numbers of days of radiotherapy interruption due to neutropenia were 0 and 3 in the experimental group and the control group, with a statistically significant difference (Z=-3.117, P=0.001). One case (4.8%) of drug-induced skeletal muscle pain was found in the experimental group and 5 cases (22.7%) in the control group, with no statistically significant difference (χ 2=1.586, P=0.208). Conclusion PEG-rhG-CSF can effectively prevent neutropenia caused by radiotherapy after postoperative chemotherapy for patients with breast cancer, and can reduce the interruption of radiotherapy and the use of rhG-CSF during radiotherapy, which is helpful to the smooth process of radiotherapy. Figures and Tables | References | Related Articles | Metrics

Bioinformatics analysis of TUBB3 expression and its regulatory mechanisms in non-small cell lung cancer Zhao Yunlong, Li Shaojun, Li Jingbo, Chen Ping, Liu Yang 2020, 47 (3):  146-150.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.004 Abstract ( 576 )   HTML ( 23 )   PDF (1809KB) ( 230 )   Save Objective To predict the expression and molecular regulatory mechanisms of βⅢ-tubulin (TUBB3) in non-small cell lung cancer (NSCLC) using bioinformatics methods. Methods The GEO profile, TransmiR, miRWalk and ConSite database were employed in the present study. The upstream transcription factor, co-expression gene and the interactive miRNA of TUBB3 were studied to determine the molecular regulatory mechanisms and possible role of TUBB3 in NSCLC. Results The promoter region of TUBB3 could be recognized by transcription factors associated with NSCLC including Snail and n-MYC and so on. At the post-transcription level, the TUBB3 could be regulated by miRNAs including miR-200 family, miR-342-3p, miR-410 and so on. These miRNAs were associated with proliferation and invasion of NSCLC. TUBB3 was co-expressed with HDGF, GMPS, MRPL9, PMAIP1 and SLBP, and they were co-regulated by the transcription factor Snail. SLBP, PMAIP1 and transcription factor Snail were related to cell cycle and apoptosis. Conclusion The expression of TUBB3 can be regulated at multiple levels in NSCLC. It may take part in cell cycle and apoptosis regulation in NSCLC, and further influence proliferation and invasion of cancer cells. Figures and Tables | References | Related Articles | Metrics

Efficacy and prognosis of palliative radiotherapy for advanced gastric cancer Zhu Ying, Zhou Danyang, Yu Dandan, Zhang Tao 2020, 47 (3):  151-156.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.005 Abstract ( 879 )   HTML ( 17 )   PDF (973KB) ( 225 )   Save Objective To investigate the efficacy and prognostic factors of palliative radiotherapy for advanced gastric cancer. Methods From January 2013 to December 2018, the clinical data of 390 patients with advanced gastric cancer in the Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected. Patients were divided into two groups—combined chemoradiotherapy group (n=95) and chemotherapy alone group (n=295) according to the treatment method. Patients were followed up by outpatient reviews, phone calls or text messages at regular intervals. The clinical efficacy and prognostic factors of palliative radiotherapy in patients with advanced gastric cancer were retrospectively analyzed. Results The median survival time and the 6-month, 1-year, 2-year survival rates of combined chemoradiotherapy group and chemotherapy alone group were respectively 28.07 months versus 11.27 months, 89.0% versus 69.0%, 68.0% versus 40.0%, 51.0% versus 15.0%. The survival rate of the combined chemoradiotherapy group was significantly higher than that of the chemotherapy alone group (χ 2=27.400, P<0.001). The median survival time of the combined chemoradiotherapy group was significantly longer than that of chemotherapy alone group in both 289 first-time diagnosed patients (χ 2=23.681, P<0.001) and 101 recurrent gastric cancer patients (χ 2=5.164, P=0.023), with median survival time being 28.07 months versus 11.47 months and 16.37 months versus 10.53 months respectively. Chemotherapy regimen before radiotherapy (χ 2=7.019, P=0.030), disease control before radiotherapy (χ 2=4.689, P=0.030), Eastern Cooperative Oncology Group (ECOG) score before radiotherapy (χ 2=8.529, P=0.014) and radiotherapy area (χ 2=4.763, P=0.029) were factors influencing the prognosis of patients with advanced gastric cancer undergoing palliative radiotherapy. Multivariate analysis showed that ECOG score (HR=2.252, 95%CI: 1.288-3.935, P=0.004) and disease control before radiotherapy (HR=2.604, 95%CI: 1.183-5.730, P=0.017) were independent prognostic factors. Conclusion The efficacy of combined chemoradio-therapy is significantly better than chemotherapy alone in both first-time diagnosed and recurrent advanced gastric cancer. Chemotherapy regimen before radiotherapy, disease control before radiotherapy, ECOG score before radiotherapy and radiotherapy area are factors influencing the prognosis of patients with advanced gastric cancer undergoing palliative radiotherapy. ECOG score and disease control before radiotherapy are independent prognostic factors. Figures and Tables | References | Related Articles | Metrics

Clinical characteristics and survival analysis of extra-upper aerodigestive tract extranodal NK/T-cell lymphoma Qi Fei, Dong Mei 2020, 47 (3):  157-163.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.006 Abstract ( 683 )   HTML ( 14 )   PDF (1361KB) ( 242 )   Save Objective To analyze the clinical characteristics, survival outcome and prognostic factors of patients with extra-upper aerodigestive tract extranodal NK/T-cell lymphoma (EUADT-ENKTCL). Methods We collected the clinical data of 779 patients with ENKTCL who were registered in SEER (Surveillance, Epidemiology, and End Results) database from 2000 to 2015 including 622 cases diagnosed with upper-aerodigestive tract extranodal NK/T-cell lymphoma (UADT-ENKTCL) and 157 cases with EUADT-ENKTCL. Clinical characteristics, survival outcome and prognostic factors were analyzed in EUADT-ENKTCL patients. Results The median age of patients with EUADT-ENKTCL was 55. The ratio of male to female was 1.85∶1. Compared with UADT-ENKTCL, patients with EUADT-ENKTCL accounted a higher proportion of malignant T-cell origin (χ 2=18.916, P<0.001), advanced stage disease (χ 2=63.669, P<0.001), accompanied B symptoms (χ 2=14.657, P=0.001) and receiving chemotherapy alone (χ 2=71.412, P<0.001). EUADT-ENKTCL could be originated in different organs and tissues throughout the body, among which the skin or subcutaneous soft tissues was the most common locations (38.2%, 60/157), followed by gastrointestinal tract (18.5%, 29/157), lung/pleura (13.4%, 21/157), testis (6.4%, 10/157), orbit (5.1%, 8/157) and others. The median overall survival (OS) was 8.0 months and 5-year OS rate was 24.0% for the EUADT-ENKTCL cohort, which were much inferior to those of UADT-ENKTCL patients (31.0 months and 43.5%; χ 2=32.080, P<0.001). Univariate analysis showed that patients with advanced stage or primary lung disease of EUADT-ENKTCL had unfavorable OS. Stage was a prognostic factor of OS via multivariate analysis (Ⅲ/Ⅳ vs. Ⅰ/Ⅱ, HR=2.078, 95%CI: 1.335-3.234, P=0.001). Conclusion EUADT-ENKTCL is a highly aggressive malignancy. Compared with UADT-ENKTCL, EUADT-ENKTCL patients have different clinical characteristics and significantly inferior OS. Figures and Tables | References | Related Articles | Metrics

Review

Relationship between HPV and oropharyngeal cancer in China Zheng Xin, Chen Xiaopin 2020, 47 (3):  164-168.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.007 Abstract ( 1386 )   HTML ( 41 )   PDF (656KB) ( 388 )   Save Oropharyngeal cancer (OPC) is one of the head and neck cancers. According to epidemiological data, the incidence and mortality of OPC in China are increasing. In addition to tobacco and alcohol, human papillomavirus (HPV) has been proved to be one of the causes of OPC. Chinese scholars have also confirmed the correlation between HPV and OPC in China, but the proportion of HPV infection in OPC in China still needs a larger sample. Because lots of studies have shown that the efficacy and prognosis of HPV-related OPC are better, the treatment of this type of patients is the current research hotspot. Meanwhile, HPV vaccine and the screening method for HPV infection in the oropharynx or oral cavity of the population deserve further research. References | Related Articles | Metrics

Current status of clinical researches on metastatic triple negative breast cancer Li Kaichun, Wang Yajie 2020, 47 (3):  169-173.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.008 Abstract ( 647 )   HTML ( 21 )   PDF (658KB) ( 265 )   Save Triple negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a poor prognosis. Median survival time of metastatic triple negative breast cancer (mTNBC) is about one year. Currently, the mainstay of treatment for mTNBC remains cytotoxic chemotherapy. In recent years, the drugs involved in the clinical researches of mTNBC include poly-ADP-ribose polymerase inhibitors, phosphoinositide 3-kinase pathway inhibitors, antibody targeting epidermal growth factor receptor, antibody targeting trophoblast surface antigen-2, antibody targeting death receptor 5, endocrine therapy drugs for androgen receptor, and immune checkpoint inhibitors and so on. New drugs have gradually improved the survival of patients with mTNBC. References | Related Articles | Metrics

Advances in radiation of internal mammary lymph nodes after breast-conserving or modified radical surgery for breast cancer Peng Caiyun, Han Chun, Wang Lan 2020, 47 (3):  174-179.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.009 Abstract ( 571 )   HTML ( 17 )   PDF (661KB) ( 273 )   Save With the development of the times, the comprehensive treatment technology of breast conserving or modified radical mastectomy plus radiotherapy for breast cancer has become more mature and perfect. As the first station of lymphatic drainage of breast, internal mammary lymph nodes have been paid much attention. At present, there is a controversy about whether the internal mammary lymph nodes are irradiated or not. Previous studies have shown that local lymph nodes irradiation containing internal mammary lymph nodes has survival benefit value. However, as a part of regional lymph nodse irradiation, internal mammary lymph nodes irradiation has also been proved to increase the toxicity of heart and lung, which leads to some research institutions and scholars to remain skeptical about internal mammary lymph nodes irradiation. In recent years, with the improvement of radiotherapy technology and equipment and the accumulation of clinical experience, more and more scholars tend to accept internal mammary lymph nodes radiotherapy. But we should pay attention to the indications of internal mammary lymph nodes irradiation, in order to select appropriate treatment options to achieve real benefits. References | Related Articles | Metrics

Research progress of KRAS mutation in lung adenocarcinoma Jin Chenxing, Zhao Yi 2020, 47 (3):  180-184.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.010 Abstract ( 960 )   HTML ( 24 )   PDF (659KB) ( 633 )   Save As the driver gene of lung cancer, Kirsten rat sarcoma viral oncogene (KRAS) mutation often occurs in lung adenocarcinoma resistant to treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which has attracted attention due to its poor prognosis and lack of targeted drugs. Recent studies have found that KRAS mutation can promote tumor progression and affect treatment and prognosis by affecting the expressions of signal transducer and activator of transcription 3 (STAT3), G-protein-coupled receptor (GPCR) and programmed death receptor-ligand 1 (PD-L1), mammalian target of rapamycin (mTOR) signaling pathway activation and co-mutation of multiple genes. A phase Ⅰ clinical trial shows that AMG 510, a novel small molecule KRAS G12C inhibitor, is hopeful in treatment. Summarizing the pathogenesis, prognostic factors, targeted therapy and immunotherapy of KRAS mutation in lung adenocarcinoma is helpful to improve the understanding of KRAS mutation and can provide ideas and basis for subsequent studies. References | Related Articles | Metrics

Application and progress of the concept of enhanced recovery after surgery in reducing surgical stress response in gastric cancer Chen Bang, Chen Bo 2020, 47 (3):  185-189.  doi: 10.3760/cma.j.issn.1673-422X.2020.03.011 Abstract ( 383 )   HTML ( 14 )   PDF (654KB) ( 270 )   Save With the further development of the concept and path of enhanced recovery after surgery (ERAS) and the confirmation of its effectiveness and feasibility in relevant studies, it has been more widely used in clinical practice. In recent years, studies have shown that ERAS is gradually applied in gastrointestinal surgery. By optimizing the diagnosis and treatment program, including preoperative preparation, anesthesia scheme, surgical procedure and postoperative rehabilitation, etc., in the perioperative period of gastric cancer, ERAS can improve the clinical diagnosis and treatment of gastric cancer patients to a certain extent, reduce the operation risk, and play an important role in reducing the postoperative stress reaction. ERAS has attracted great attention in order to accelerate the recovery of gastric cancer after surgery. References | Related Articles | Metrics