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08 April 2022, Volume 49 Issue 4 Previous Issue    Next Issue

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MiR-219a-5p inhibits the proliferation, invasion and migration of osteosarcoma U2OS cells by negatively regulating HMGA2 Zhou Renbang, Zhang Zhongchuan, Xu Zhiyuan, Zhu Xunbing 2022, 49 (4):  193-198.  doi: 10.3760/cma.j.cn371439-20220303-00034 Abstract ( 258 )   HTML ( 42 )   PDF (2152KB) ( 103 )   Save Objective To investigate the effects of miR-219a-5p on proliferation, invasion and migration of osteosarcoma U2OS cells by regulating high mobility group A2 （HMGA2）. Methods Real-time quantitative PCR was used to detect miR-219a-5p mRNA expression levels in osteosarcoma U2OS cells and normal osteoblasts hFOB1.19. The U2OS cells were transfected with miR-219a-5p mimic （miR-219a-5p mimic group） and negative control mimic （mimic NC group） by liposome transfection. The expression levels of miR-219a-5p and HMGA2 mRNA in transfected cells were detected by real-time quantitative PCR. The level of HMGA2 protein was detected by Western blotting, cell proliferation ability was detected by CCK-8 assay and clonogenesis assay, cell migration ability was detected by scratching assay, cell invasion ability was detected by Transwell chamber assay, and the relationship between miR-219a-5p and HMGA2 was verified by double luciferase reporter gene assay. Results Real-time quantitative PCR showed that the expression level of miR-219a-5p in osteosarcoma U2OS cells （0.11±0.01） was significantly lower than that in normal osteoblasts （1.00±0.06）, with a statistically significant difference （t=26.83, P<0.001）. The results of CCK-8 showed that the cell absorbance values of the mimic NC group and miR-219a-5p mimic group were 0.52±0.02 and 0.42±0.02 after 24 h, 0.85±0.03 and 0.60±0.03 after 48 h, and 1.12±0.02 and 0.72±0.02 after 72 h respectively. The proliferation activity of the miR-219a-5p mimic group was significantly lower than that of the mimic NC group, with statistically significant differences （t=6.97, P<0.001; t=16.65, P<0.001; t=26.78, P<0.001）. The results of clonogenesis assay showed that the number of clones in the miR-219a-5p mimic group was 157.00±15.39, which was significantly lower than that in the mimic NC group （294.00±15.51）, with a statistically significant difference （t=9.70, P<0.001）. The results of scratch experiment showed that the percentage of scratch area in the miR-219a-5p mimic group was （40.53±2.92）% after 24 h culture, which was significantly higher than that in the mimic NC group [（21.71±3.11）%], with a statistically significant difference （t=7.26, P=0.002）. The results of Transwell chamber assay showed that the number of cells penetrating the membrane in the miR-219a-5p mimic group was 128.67±18.67, which was significantly lower than that in the mimic NC group （317.67±14.33）, with a statistically significant difference （t=15.65, P<0.001）. The results of double luciferase reporter gene assay showed that in MUT-HMGA2 cells, transfection with miR-219a-5p mimic （4.30±0.26） had no significant effect on luciferase activity compared with the mimic NC group （4.40±0.28）, with a statistically significant difference （t=0.85, P=0.690）. In WT-HMGA2 cells, compared with the mimic NC group （4.50±0.25）, the lucifase activity of the miR-219a-5p mimic group （2.88±0.16） was significantly decreased, with a statistically significant difference （t=19.15, P<0.001）. After miR-219a-5p was overexpressed, HMGA2 mRNA and protein expressions in osteosarcoma U2OS cells （0.77±0.01; 0.37±0.01） were downregulated compared with the mimic NC group （1.00±0.02; 1.00±0.01）, with statistically significant differences （t=16.38, P<0.001; t=42.02, P<0.001）. Conclusion In osteosarcoma cells, miR-219a-5p can inhibit the proliferation, migration and invasion of osteosarcoma cells by down regulating the expression of HMGA2. Figures and Tables | References | Related Articles | Metrics

Effects of sarcopenia on the clinical efficacy and prognosis of radical radiotherapy in elderly patients with esophageal cancer Ye Qian, Ling Zhi, Liu Shenxiang, Lu Guotao, Yin Xudong 2022, 49 (4):  199-205.  doi: 10.3760/cma.j.cn371439-20210526-00035 Abstract ( 242 )   HTML ( 22 )   PDF (768KB) ( 118 )   Save Objective To explore the relationships between sarcopenia and the clinical efficacy and prognosis of elderly patients with esophageal cancer who were treated by radical radiotherapy. Methods The clinicopathological data of 134 elderly patients with esophageal cancer who received radical radiotherapy in Department of Radiotherapy, Affiliated Hospital of Yangzhou University from January 2013 to December 2018 were retrospectively analyzed. The muscle cross-sectional area at the level of the third lumbar vertebra was measured by using computed tomography （CT） images. These patients were divided into sarcopenia group （n=56） and non-sarcopenia group （n=78） according to the skeletal muscle index before radiotherapy. The efficacy and incidence of adverse reactions of the two groups were compared. Kaplan-Meier method was used to plot the survival curve, and Cox regression model was used to analyze prognostic factors. Results There was a significant difference in the objective response rate between the sarcopenia and non-sarcopenia group at 1 month after radiotherapy [53.57% （30/56） vs. 71.79% （56/78）, χ2=4.71, P=0.030]. There was no significant difference in the disease control rate between the two groups [94.64% （53/56） vs. 91.03% （71/78）, χ2=0.21, P=0.651]. There was a significant difference in the total incidence of adverse reactions between the sarcopenia and non-sarcopenia group [67.86% （38/56） vs. 47.44% （37/78）, χ2=5.52, P=0.019]. By the end of the follow-up, the 1-, 3- and 5-year overall survival （OS） rates of 134 elderly patients with esophageal cancer who received radical radiotherapy were 91.0%, 73.1% and 55.2% respectively. The median OS of patients in the sarcopenia and non-sarcopenia group were 14 months and 26 months respectively, with a statistically significant difference （χ2=9.84, P=0.002）. The median progression-free survival （PFS） of the two groups were 7 months and 18 months respectively, with a statistically significant difference （χ2=9.91, P=0.002）. Univariate analysis showed that cT stage （HR=2.45, 95%CI： 1.26-4.74, P=0.008）, cN stage （HR=1.63, 95%CI：1.06-2.50, P=0.027）, cTNM stage （HR=2.04, 95%CI： 1.28-3.27, P=0.003）, body mass index （BMI） （HR=2.23, 95%CI： 1.01-4.90, P=0.046）, pre-radiotherapy sarcopenia （HR=2.45, 95%CI： 1.27-4.72, P=0.007） and chemotherapy （HR=0.30, 95%CI： 0.11-0.83, P=0.020） were prognostic factors for OS; cT stage （HR=2.27, 95%CI： 1.18-4.39, P=0.015）, cN stage （HR=1.61, 95%CI： 1.04-2.47, P=0.030）, cTNM stage （ HR=1.90, 95%CI： 1.19-3.02, P=0.007）, BMI （HR=1.98, 95%CI： 1.06-3.79, P=0.032）, pre-radiotherapy sarcopenia （HR=1.79, 95%CI： 1.06-3.04, P=0.031） and adverse reactions （HR=0.60, 95%CI： 0.38-0.97, P=0.037） were prognostic factors for PFS. Multivariate analysis showed that pre-radiotherapy sarcopenia （HR=1.91, 95%CI： 1.22-3.00, P=0.005） was an independent prognostic factor for OS; BMI （HR=1.80, 95%CI： 1.03-3.15, P=0.039） and pre-radiotherapy sarcopenia （HR=2.00, 95%CI： 1.27-3.14, P=0.003） were independent prognostic factors for PFS. Conclusion Sarcopenia before radiotherapy can be a useful predictor for prognosis in elderly patients with esophageal cancer who received radical radiotherapy, and patients with sarcopenia benefit less from treatment. Figures and Tables | References | Related Articles | Metrics

Genetic susceptibility genes and clinical features of early-onset breast cancer Li Lixi, Wen Tingyu, Guan Xiuwen, Zhai Jingtong, Ma Fei 2022, 49 (4):  206-209.  doi: 10.3760/cma.j.cn371439-20220221-00036 Abstract ( 253 )   HTML ( 19 )   PDF (687KB) ( 73 )   Save Objective To explore the germline mutation frequency of genetic susceptibility genes and clinical characteristics in early-onset breast cancer （onset age ≤35 years） in China. Methods Clinical information and peripheral blood of 150 patients aged 35 and younger diagnosed with breast cancer in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to December 31, 2019 were collected. Then DNA was extracted to detect germline mutations in breast cancer susceptibility gene （BRCA）1, BRCA2, ataxia telangiectasia mutated （ATM）, partner and localizer of BRCA2 （PALB2）, tumor protein 53 （TP53） and cell cycle checkpoint kinase 2 （CHEK2） genes. Mutations were interpreted as pathogenic, likely pathogenic, uncertain significance, likely benign and benign according to the classification criteria and guidelines for genetic variation. Patients were divided into mutation group （n=18） and non-mutation group （n=132） according to the presence or absence of pathogenic or probable pathogenic germline mutations, and the χ2 test was used to analyze the relationships between genetic susceptibility gene mutations and clinicopathological characteristics. Results Eighteen pathogenic or likely pathogenic germline mutations were detected in 150 patients with early-onset breast cancer, for an overall mutation frequency of 12.0%. Among them, there were 8 （5.3%） BRCA2 mutation, 7 （4.7%） BRCA1 mutation, 1 （0.7%） PALB2 mutation, and 2 （1.3%） TP53 mutation. There were no pathogenic or likely pathogenic variants in ATM and CHEK2 genes. The mutation type was dominated by frameshift mutation （9/18, 50.0%）, followed by nonsense mutation （7/18, 38.9%）, missense mutation （1/18, 5.6%） and splice acceptor mutation（1/18,5.6%）. Among the molecular subtypes of 18 mutation carriers, 9 cases were Luminal B, 6 cases were triple negative breast cancer （TNBC）, 2 cases were Luminal A, and only 1 case was human epidermal growth factor receptor-2 （HER-2） amplification. Among them, 8 BRCA2 mutation carriers were Luminal type, and 6 of 7 BRCA1 mutation carriers were TNBC type. There were no statistical differences in family history of breast cancer （P=0.343）, estrogen receptor （ER） status （χ2=0.16, P=0.688）, HER-2 status （χ2=2.89, P=0.089）, molecular subtype （χ2=1.99, P=0.575）, and initial diagnosis TNM stage （χ2=2.49, P=0.115） between the mutation group and the non-mutation group. Conclusion The patients with early-onset breast cancer have high frequency of germline mutations. It is recommended that patients with early-onset breast cancer undergo genetic counseling and multigene testing. Figures and Tables | References | Related Articles | Metrics

Predictive value of systemic inflammation response index before treatment for pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy Liu Yonghong, Xue Lingbo, Bai Yang, Jin Jian, Zang Chunxia, Zhang Bo, Li Jie 2022, 49 (4):  210-215.  doi: 10.3760/cma.j.cn371439-20210813-00037 Abstract ( 268 )   HTML ( 25 )   PDF (933KB) ( 84 )   Save Objective To investigate the predictive value of systemic inflammation response index （SIRI） before treatment for pathological complete response （pCR） in patients with breast cancer undergoing neoadjuvant chemotherapy. Methods The clinicopathological data of 119 patients with primary breast cancer undergoing neoadjuvant chemotherapy and subsequent breast-conserving or modified radical surgery from Cangzhou Central Hospital of Hebei Province between January 2010 to March 2020 were retrospectively analyzed, and patients were divided into pCR group （n=19） and non-pCR group （n=100） based on postoperative pathology. The SIRI before treatment between the two groups was compared. The patients were divided into SIRI≤0.25 （n=10）, 0.26-0.50 （n=42）, 0.51-0.75 （n=29）, 0.76-1.00 （n=19）, and >1.00 （n=19） groups according the SIRI before treatment, and the pCR ratios of the five groups were compared. Spearman correlation analysis was applied to evaluate the relationship between SIRI before treatment and pCR, logistic regression analysis was used to identify the influencing factors of pCR for neoadjuvant chemotherapy in breast cancer patients, and receiver operating characteristic （ROC） curve was used to evaluate the predictive value of SIRI before treatment for pCR of neoadjuvant chemotherapy in breast cancer patients. Results Tumor size （Z=2.26, P=0.024）, axillary lymph node metastasis （χ2=5.73, P=0.017）, human epidermal growth factor receptor-2 （HER-2） （χ2=8.77, P=0.003）, Ki-67 （Z=2.68, P=0.007）, cytological nuclear grade （χ2=5.08, P=0.024）, neutrophil count before treatment （Z=2.44, P=0.015）, monocyte/lymphocyte ratio before treatment （Z=3.04, P=0.002）, and SIRI before treatment （Z=3.29, P=0.001） had statistical differences between the pCR and non-pCR groups. The pCR ratios were 50% （5/10） in the SIRI ≤0.25 group, 21% （9/42） in the 0.26-0.50 group, 10% （3/29） in the 0.51-0.75 group, 11% （2/19） in the 0.76-1.00 group, and 0 （0/19） in the >1.00 group, with a statistic difference （χ2=14.28, P=0.006）. SIRI before treatment was negatively related with pCR （r=-0.30, P=0.001）. Univariate logistic regression analysis showed that tumor size （OR=0.50, 95%CI： 0.28-0.89, P=0.019）, axillary lymph node metastasis （OR=5.43, 95%CI： 1.19-24.83, P=0.029）, HER-2 （OR=7.54, 95%CI： 1.65-34.36, P=0.009）, Ki-67 （OR=1.03, 95%CI： 1.01-1.05, P=0.008）, cytological nuclear grade （OR=0.20, 95%CI： 0.04-0.92, P=0.038）, neutrophil count before treatment （OR=0.54, 95%CI： 0.32-0.92, P=0.023）, monocyte/lymphocyte ratio before treatment （OR=0.00, 95%CI： 0.00-0.01, P=0.007）, and SIRI before treatment （OR=0.03, 95%CI： 0.00-0.37, P=0.007） were influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. Multivariate logistic regression analysis confirmed that tumor size （OR=0.31, 95%CI： 0.14-0.72, P=0.007）, axillary lymph node metastasis （OR=10.97, 95%CI： 1.35-89.61, P=0.025）, HER-2 （OR=6.47, 95%CI： 1.18-35.65, P=0.032）, Ki-67 （OR=1.04, 95%CI： 1.00-1.07, P=0.029）, cytological nuclear grade （OR=7.87, 95%CI： 1.01-61.35, P=0.049）, and SIRI before treatment （OR=0.03, 95%CI： 0.00-0.58, P=0.020） were independent influencing factors for pCR of neoadjuvant chemotherapy in breast cancer patients. The ROC curve showed that the area under the curve of SIRI before treatment for predicting pCR was 0.74 （95%CI： 0.65-0.82）, sensitivity was 68.0%, and specificity was 75.3%. The area under the curve of monocyte/lymphocyte ratio before treatment for predicting pCR was 0.72 （95%CI： 0.63-0.80）, sensitivity was 48.0%, and specificity was 84.2%. The area under the curve of neutrophil count before treatment for predicting pCR was 0.68 （95%CI： 0.59-0.76）, sensitivity was 61.0%, and specificity was 83.7%. Conclusion SIRI before treatment may serve as a marker for predicting pCR in patients with breast cancer undergoing neoadjuvant chemotherapy,patients with low SIRI are more likely to obtain pCR. Figures and Tables | References | Related Articles | Metrics

Reviews

Gasdermin E and neoplasms Ma Meijie, Ma Huihan, Mi Jiaqing, Qin Qian, Feng Qinmei 2022, 49 (4):  216-219.  doi: 10.3760/cma.j.cn371439-20210520-00038 Abstract ( 229 )   HTML ( 22 )   PDF (678KB) ( 83 )   Save Gasdermin E is closely related to neoplasms, which is involved in the occurrence and development of neoplasms through gene methylation, gene mutation or other ways. Pyroptosis mediated by gasdermin E is involved in drug therapy of various neoplasms, which provides a new theoretical basis for drug therapy of neoplasms. The study of gasdermin E aims to deepen the understanding of neoplasms and provide a new perspective for the prevention and treatment of neoplasms. References | Related Articles | Metrics

Adverse reactions and treatment measures of advanced solid tumors treated with antibody-drug conjugates Pang Jingdan, Du Yingying, Da Jie 2022, 49 (4):  220-224.  doi: 10.3760/cma.j.cn371439-20220208-00039 Abstract ( 259 )   HTML ( 18 )   PDF (692KB) ( 134 )   Save Novel antibody-drug conjugates （ADCs） are a hot spot in the research and development of new drugs for advanced solid tumors. ADCs have achieved significant efficacy in the treatment of advanced breast cancer, urothelial carcinoma, gastric cancer and other solid tumors, but their adverse reactions such as ocular toxicity, pulmonary toxicity, hematological toxicity, and liver toxicity cannot be ignored, and it is crucial to effectively deal with the adverse reactions of ADCs. References | Related Articles | Metrics

Research progress on the correlation between dermatological immune-related adverse events and clinical outcome of PD-1/PD-L1 inhibitors Ding Xinjing, Ding Jianghua 2022, 49 (4):  225-228.  doi: 10.3760/cma.j.cn371439-20210604-0040 Abstract ( 202 )   HTML ( 25 )   PDF (682KB) ( 126 )   Save Immunotherapy represented by PD-1/PD-L1 inhibitors has become the main treatment of malignant tumors. However,the adverse events caused by immunotherapy can not be ignored. Among them,dermatological immune-related adverse events （irAEs） occur with the highest incidence. Most dermatological irAEs belong to grade Ⅰ-Ⅱ, which does not affect the application of PD-1/PD-L1 inhibitors. The pathogenesis of dermatological irAEs is not fully understood. The most common types of dermatological irAEs are rash,pruritus and vitiligo. The domestic PD-1 inhibitor camrelizumab has unique adverse reactions of reactive cutaneous capillary endothelia proliferation （RCCEP）. It is found that dermatological irAEs can predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant melanoma and non-small cell lung cancer （NSCLC）,especially RCCEP can be used as a potential biomarker of the efficacy of camrelizumab in the treatment of NSCLC, hepatocarcinoma, and esophageal cancer. References | Related Articles | Metrics

Research progress on downgrading therapy for HPV positive oropharyngeal carcinoma Wang Qi, Wang Lan, Han Chun 2022, 49 (4):  229-232.  doi: 10.3760/cma.j.cn371439-20210428-00041 Abstract ( 307 )   HTML ( 11 )   PDF (678KB) ( 79 )   Save Previous studies have shown that patients with human papilloma virus（HPV）-positive oropharyngeal cancer have a significantly better prognosis than patients with HPV-negative oropharyngeal cancer. However, the high incidence of severe adverse reactions in patients with oropharyngeal cancer under the standard treatment mode affects the sustainability of treatment. At present, internal and overseas studies have indicated that step-down therapy is the trend of future treatment for HPV-associated oropharyngeal cancer, and the step-down therapy mode of these patients is also a hotspot of current research. Reducing the intensity of chemotherapy, reducing the intensity of radiotherapy, and reducing the dose of radiotherapy and chemotherapy through the combination therapy mode provide further research directions for the step-down therapy of HPV-associated oropharyngeal cancer. References | Related Articles | Metrics

Advances in non-operative treatment of advanced hypopharyngeal squamous cell carcinoma Zhang Rui, Feng Enzi, Ren Yanxin, Li Xiaojiang 2022, 49 (4):  233-236.  doi: 10.3760/cma.j.cn371439-20210520-00042 Abstract ( 373 )   HTML ( 12 )   PDF (679KB) ( 103 )   Save Hypopharyngeal squamous cell carcinoma has a high degree of malignancy, hidden location, atypical early symptoms, most patients have reached advanced stage at the time of treatment. Surgical treatment will cause patients to lose laryngeal function and poor postoperative quality of life. The combined application of non-operative therapies such as radiotherapy and chemotherapy can improve the larynx preservation rate of patients and obtain a survival rate similar to that of surgical treatment. Targeted therapy has achieved better results in the treatment of hypopharyngeal squamous cell carcinoma, and immunotherapy has also made great progress in the treatment of head and neck squamous cell carcinoma, which brings new hope for patients with hypopharyngeal squamous cell carcinoma. References | Related Articles | Metrics

Targeted therapy and immunotherapy of esophageal cancer Zhou Jianfeng, Wang Tiejun 2022, 49 (4):  237-242.  doi: 10.3760/cma.j.cn371439-20210520-00043 Abstract ( 305 )   HTML ( 25 )   PDF (698KB) ( 151 )   Save Esophageal cancer is a complex digestive tract cancer. Currently, the study of radiotherapy and chemotherapy for non-surgical esophageal cancer has reached the bottleneck. In recent years, with the in-depth study of tumor signal pathway related targets and immunotherapy, tumor treatment methods are becoming more and more diversified. At present, research shows that a variety of gene targets and immune receptors are related to esophageal cancer, including epidermal growth factor receptor, vascular endothelial growth factor, human epidermal growth factor receptor 2, programmed death-1/programmed death ligand-1, etc. In addition, tumor vaccine and adoptive cell therapy are also being studied. These factors contribute to the individualized and accurate treatment of esophageal cancer and improve survival rate and local control rate. References | Related Articles | Metrics

Potential value of radiotherapy combined with immunotherapy in breast cancer brain metastases Sun Xiaolin, Zhang Zhanyu, Xu Linzong, Liu Yingchao, Li Xiaomei 2022, 49 (4):  243-246.  doi: 10.3760/cma.j.cn371439-20220208-00044 Abstract ( 238 )   HTML ( 27 )   PDF (686KB) ( 114 )   Save With the increasing understanding of the unique tumor microenvironment in the brain, immunotherapy have emerged as a new and promising treatment for brain metastases. Radiotherapy and immunotherapy have a synergistic effect, and it is of great value to understand its mechanism in the treatment of breast cancer brain metastases. At present, the study of immune checkpoint inhibitors combined with radiotherapy in breast cancer brain metastases is being actively carried out, bringing new hope to patients with breast cancer brain metastases. References | Related Articles | Metrics

Application of microbiota in the early diagnosis and adjunctive treatment of lung cancer Gao Min, Feng Jing, Wang Li, Zhong Hai, Wen Yuting, Wan Bing, Zhang Xiuwei 2022, 49 (4):  247-251.  doi: 10.3760/cma.j.cn371439-20220208-00045 Abstract ( 210 )   HTML ( 18 )   PDF (688KB) ( 101 )   Save Drug-resistance and adverse reaction in the treatment of lung cancer patients are still a difficult problem in modern medicine. Studies have indicated that the abundance,diversity and metabolites of intestinal and pulmonary microbiota can be used to assist in the early diagnosis and monitoring the prognosis of lung cancer. Meanwhile, as combined modality therapies, intestinal microbiota combined with chemotherapy, immunotherapy and targeted therapy can enhance therapeutic effect and reduce adverse reaction. Microbiota exhibits an extensive application prospect in the diagnosis and treatment of lung cancer. References | Related Articles | Metrics