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    08 September 2020, Volume 47 Issue 9 Previous Issue    Next Issue
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    Original Articles
    Serum proteomic-based analysis identifying autoantibody against ENO1 as a potential diagnostic biomarker in nasopharyngeal carcinoma
    Zhan Xiaofen, Weng Xuefen, Yang Shihuang, Xu Yiwei, Peng Yuhui, Guo Hong
    2020, 47 (9):  513-517.  doi: 10.3760/cma.j.cn371439-20191223-00069
    Abstract ( 487 )   HTML ( 36 )   PDF (1027KB) ( 270 )   Save

    Objective To screen and identify autoantibody biomarker to diagnose patients with nasopharyngeal carcinoma (NPC). Methods Candidate autoantibodies against tumor-associated antigens were identified from NPC CNE2 cells using serological proteome analysis. Levels of candidate autoantibody biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) in 50 patients with NPC and 80 normal controls recruited from the Cancer Hospital of Shantou University Medical College between July 2014 and January 2015. Receiver operating characteristic curve (ROC) was employed to evaluate diagnostic efficacy. Results Serological proteome analysis showed that sera from patients with NPC yielded a positive spot, of which was identified as enolase 1 (ENO1). ELISA results showed that the level of serum autoantibody against ENO1 in patients with NPC was significantly higher than that in normal controls [0.165 (0.088, 0.378) vs. 0.100 (0.054, 0.117), Z=4.077, P<0.001]. With the optimum diagnostic cutoff of 0.164, ROC curve showed the diagnostic sensitivity and specificity of autoantibodies against ENO1 were 52.0% and 90.0%, respectively. Measurement of autoantibody against ENO1 demonstrated a positive rate of 75.0% for early stage NPC. Conclusion Autoantibody against ENO1 may be a potential diagnostic biomarker for NPC.

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    Clinical observation of elemene injection in perioperative treatment of esophageal cancer
    Zhang Xixuan, Zhou Bin, Wang Haibo, Gong Qiang, Li Ben, Guo Qiang, Li Hefei
    2020, 47 (9):  518-523.  doi: 10.3760/cma.j.cn371439-20200402-00070
    Abstract ( 478 )   HTML ( 27 )   PDF (644KB) ( 241 )   Save

    Objective To observe the clinical effect of elemene injection in the perioperative treatment of esophageal cancer. Methods A total of 180 patients with esophageal cancer who underwent surgical treatment in the Affiliated Hospital of Hebei University from January 2017 to July 2018 were selected and divided into the experimental group (n=90) and the control group (n=90) according to the random sequence number generated by the computer. In the experimental group, the thoracic cavity was rinsed and the elemene was instilled and intravenously instilled. The control group was treated with normal saline. Safety indexes, short-term efficacy indexes, immune indexes, tumor marker levels and long-term benefit indexes were observed in the two groups. Results The incidences of leukocytosis, thrombocytopenia, low hemoglobin, elevated creatinine, transaminase elevation, nausea and vomiting in the experimental group were 43.33% (39/90), 0 (0/90), 5.55% (5/90), 6.67% (6/90), 4.44% (4/90) and 0 (0/90), those in the control group were 53.33% (48/90), 1.11% (1/90), 2.22% (2/90), 4.44% (4/90), 7.78% (7/90) and 1.11% (1/90), and there were no significant differences between the two groups (χ2=1.802, P=0.179; P=1.000; χ2=0.595, P=0.441; χ2=0.424, P=0.515; χ2=0.871, P=0.351; P=1.000). The postoperative extubation time in the experimental group was (173.36±41.09) h, the postoperative hospital stay was (14.82±4.35) d, the Karnofsky functional status (KPS) score was 81.43±3.89, and those in the control group was (175.76±40.46) h, (15.34±5.22) d and 80.49±2.67, respectively. The differences between the two groups were not statistically significant (t=-0.395, P=0.695; t=-0.726, P=0.472; t=1.890, P=0.061). The total amount of drainage fluid in the experimental group was (665.39±201.31) ml, and the incidence of anastomotic fistula was 1.11% (1/90), which were significantly lower than those in the control group [(732.67±213.84) ml and 8.89% (8/90)], with statistically significant differences (t=-2.173, P=0.032; χ2=4.211, P=0.040). Before treatment, there were no statistically significant differences in immune function between the two groups (all P>0.05). One week after surgery, there was no statistically significant difference in CD3+ between the two groups [(55.45±6.96)% vs. (53.71±6.54)%, t=1.728, P=0.087]; CD4+, CD4+/CD8+ and NK cells in the experimental group were higher than those in the control group, and the differences were statistically significant [(29.43±5.05)% vs. (25.92±8.06)%, t=3.501, P=0.001; 1.30±0.21 vs. 1.23±0.20, t=0.229, P=0.028; (254.20±15.21)/μl vs. (237.05±10.73)/μl, t=2.741, P=0.007]. The levels of tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the experimental group were (1.37±0.18) ng/ml, (1.26±0.28) ng/ml, (0.89±0.17) ng/ml and (1.06±0.24) ng/ml, significantly lower than those in the control group [(2.86±0.42) ng/ml, (2.92±0.45) ng/ml, (2.38±1.55) ng/ml, (2.82±0.15) ng/ml], and the differences were statistically significant (t=13.928, P=0.014; t=19.728, P=0.011; t=17.924, P=0.006; t=16.625, P=0.003). The 1-year recurrence rate was 2.22% (2/90) in the experimental group, and the half-year mortality rate was 1.11% (1/90) in the experimental group, and 5.56% (5/90) and 2.22% (2/90) in the control group, with no statistically significant differences (χ2=0.595, P=0.441; χ2=0.000, P=1.000). Conclusion Elemene tumor-free sequential treatment combined with postoperative intravenous drip has a positive effect on postoperative recovery of patients with esophageal cancer, which can prevent the occurrence of postoperative anastomotic fistula, improve patients' immune function, reduce the levels of tumor markers, and it is safe and feasible.

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    Distribution of naïve T cell and memory T cell subsets in peripheral blood of non-small cell lung cancer patients
    Liu Yunhe, Li Wentao, Yu Jianchun
    2020, 47 (9):  524-529.  doi: 10.3760/cma.j.cn371439-20200113-00071
    Abstract ( 596 )   HTML ( 26 )   PDF (1550KB) ( 324 )   Save

    Objective To investigate the distribution of naïve T cell and memory T cell subsets in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Methods A total of 25 NSCLC patients from the Oncology Department of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June to December 2018 were included in the study, and 20 healthy volunteers in the same period were used as controls. Flow cytometry was used to analyze the naïve T cell and memory T cell subsets in peripheral blood. The results were analyzed by SPSS 16.0. Results The percentage and absolute number of naïve T cell/stem-like central memory T cells (TN/SCM) in NSCLC patients declined compared to the control group [(7.71±1.11)% vs. (15.84±2.00)%, t=3.685, P=0.001; (8.38±1.23)×107/L vs. (3.40±0.43)×108/L, t=6.130, P<0.001]. The percentage and absolute number of central memory T cells (TCM) in NSCLC patients declined compared to the control group [(6.62±1.16)% vs. (17.88±0.83)%, t=7.641, P<0.001; (7.98±1.78)×107/L vs. (3.40±0.31)×108/L, t=9.028, P<0.001]. The absolute number of CD8+TCM in NSCLC patients declined compared to the control group [(5.19±1.04)×106/L vs. (1.49±0.15)×107/L, t=5.561, P<0.001]. The percentage of effector memory T cells (TEM) in NSCLC patients increased compared to the control group [(38.27±2.01)% vs. (17.37±1.06)%, t=8.776, P<0.001]. The percentage and absolute number of CD8+TEM in NSCLC patients increased compared to the control group [(13.93±1.55)% vs. (4.65±0.52)%, t=5.310, P<0.001; (1.48±0.14)×108/L vs. (9.97±1.14)×107/L, t=2.584, P=0.014]. The percentage of effector memory T cells re-expressing CD45RA (TEMRA) in NSCLC patients increased compared to the control group [(17.33±1.86)% vs. (8.48±1.01)%, t=3.989, P<0.001]. The percentage and absolute number of CD8+TCM in stage Ⅰ-Ⅱ patients declined compared to stage Ⅲ-Ⅳ patients [(0.33±0.06)% vs. (0.89±0.34)%, t=2.600, P=0.020; (3.99±0.84)×106/L vs. (9.03±3.07)×106/L, t=2.270, P=0.040]. There were no statistically significant differences in the naïve T cells and memory T cell subsets of NSCLC patients with different pathological types. Conclusion In NSCLC patients, the naïve/memory T cell subsets are changed compared with the healthy volunteers. The TN/SCM and TCM those with the characteristics of differentiation ability and long-term survival are reduced, and those of the stage Ⅰ-Ⅱ patients are reduced significantly. TEM and TEMRA with immunological effect are increased significantly.

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    Anti-tumor effect of berberine hydrochloride combined with epirubicin and cisplatin on advanced endometrial carcinoma
    Huang Yuting, Wang Chao
    2020, 47 (9):  530-534.  doi: 10.3760/cma.j.cn371439-20191219-00072
    Abstract ( 454 )   HTML ( 24 )   PDF (639KB) ( 296 )   Save

    Objective To observe the anti-tumor effect of berberine hydrochloride combined with epirubicin and cisplatin on advanced endometrial carcinoma (EC). Methods A total of 120 patients with advanced EC admitted to Chaohu Hospital of Anhui Medical University from January 2016 to December 2018 were enrolled. The patients were divided into experimental group and control group by random number table method, 60 cases in each group. The control group was given intravenous infusion of epirubicin and cisplatin. The experimental group was given oral berberine hydrochloride on the basis of control group treatment, 21 days/cycle for 6 cycles. The clinical efficacy, changes of serum tumor markers, incidence of adverse reactions, 1-year mortality rate of the two groups were counted and compared. Results The distribution of clinical efficacy grades in the two groups was significantly different (Z=4.489, P=0.042), and the total effective rate of the experimental group was 63.33% (38/60), which was higher than that of 45.00% (27/60) in the control group (χ2=4.062, P=0.044). The levels of carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carcino-embryonic antigen (CEA) in the experimental group after treatment were (30.01±6.05) U/ml, (40.38±7.61) U/ml and (16.85±3.08) ng/ml respectively, which in the control group were (45.83±6.91) U/ml, (48.89±8.05) U/ml and (20.20±4.18) ng/ml respectively. The levels of CA125, CA19-9, CEA in both groups after treatment decreased compare with those before treatment, which in the experimental group after treatment were lower than those in the control group, with statistically significant differences (t=13.343, P<0.001; t=5.951, P<0.001; t=4.998, P<0.001). The incidences of liver dysfunction, renal dysfunction, leukopenia, thrombocytopenia, nausea/vomiting, diarrhea, oral mucositis and total adverse reaction in the experimental group were 8.33% (5/60), 5.00% (3/60), 6.67% (4/60), 6.67% (4/60), 8.33% (5/60), 1.67% (1/60), 3.33% (2/60), 40.00% (24/60), which were 6.67% (4/60), 3.33% (2/60), 8.33% (5/60), 6.67% (4/60), 8.33% (5/60), 0 (0/60), 1.67% (1/60), 35.00% (21/60) in the control group, without statistically significant differences (χ2=0.000, P=1.000; χ2=0.000, P=1.000; χ2=0.000, P=1.000; χ2=0.134, P=0.714; χ2=0.109, P=0.741; P=1.000; χ2=0.000, P=1.000; χ2=0.320, P=0.572). After 1 year of following-up, the mortality rate of the control group was 8.33% (5/60), and the mortality rate of the experimental group was 5.00% (3/60), and there was no significant difference between the two groups (χ2=0.134, P=0.714). Conclusion Berberine hydrochloride combined with epirubicin and cisplatin is effective in treatment of advanced EC, which can decrease tumor marker levels, and it is safe and reliable of clinical reference.

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    Clinical analysis of 93 cases of adult patients with acute lymphoblastic leukemia
    Xu Lei, Dai Jing, Zhang Qian, Zhang Wenli, Li Jinmeng, Zhang Hongyu
    2020, 47 (9):  535-541.  doi: 10.3760/cma.j.cn371439-20200725-00073
    Abstract ( 557 )   HTML ( 24 )   PDF (1310KB) ( 330 )   Save

    Objective To analyze the survival and prognostic factors of adult acute lymphoblastic leukemia (ALL) with different consolidation regimens after complete remission by induction therapy. Methods A total of 93 adult patients with ALL were enrolled from January 2012 to June 2019 in Peking University Shenzhen Hospital. All the patients achieved complete remission induced by VDLCP regimen, and were divided into the standard group, intensive group and transplantation group according to the consolidation treatment. Thirty-four patients in the standard group received an ALL-like chemotherapy regimen based on VDLCP or Hyper-CVAD consolidation for 4-6 courses. Twenty-nine patients in the intensive group received BFM90/95 consolidation treatment for 2 years. Thirty patients in the transplantation group received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after 2-3 courses of consolidation with the original induction regimen. The median follow-up was 18 (3-96) months, and the main follow-up indicators were overall survival (OS) and disease free survival (DFS). Prognostic factors of adult ALL patients and treatment-related deaths in each group were analyzed. Results The 3-year OS rates of the standard group, intensive group and transplantation group were 54.0% (95%CI: 35.3%-72.6%), 71.8% (95%CI: 41.0%-94.5%), 62.3% (95%CI: 43.6%-80.9%), with a statistically significant difference (χ2=6.110, P=0.047). The 3-year DFS rates of the three groups were 31.4% (95%CI: 12.9%-49.8%), 72.1% (95%CI: 52.3%-91.9%), 65.7% (95%CI: 45.3%-86.1%), with a statistically significant difference (χ2=13.831, P=0.001). There were no significant differences in OS and DFS between the intensive group and the transplantation group (χ2=0.709, P=0.400; χ2=0.046, P=0.830). OS and DFS of the intensive group were better than those of the standard group (χ2=5.346, P=0.021; χ2=10.326, P=0.010). Multivariate analysis suggested that bone marrow minimal residual disease (MRD) negative on day 14-21 of chemotherapy was an independent prognostic factor affecting adult ALL (HR=0.114, 95%CI: 0.015-0.841, P=0.033). The 3-year OS rates of Ph+ALL patients who received and did not receive allo-HSCT were 53.5% (95%CI: 23.1%-83.8%), 52.4% (95%CI: 23.8%-81.0%), the 3-year DFS rates were 77.1% (95%CI: 54.2%-100.0%), 35.0% (95%CI: 4.8%-65.2%), and there were no significant differences between the two groups (χ2=3.600, P=0.223; χ2=3.824, P=0.050). The treatment-related mortalities of the non-transplantation group (standard group + intensive group) and the transplantation group were 3.2% (2/63) and 20.0% (6/30), and the treatment-related mortality of the non-transplantation group was significantly lower than that of the transplantation group (χ2=7.318, P=0.007). Conclusion Adult ALL has a poor prognosis. The 3-year OS rate and 3-year DFS rate of BFM intensive consolidation therapy are better than those of standard consolidation therapy, achieving a similar effect to allo-HSCT, but treatment-related mortality does not increase significantly. Patients with bone marrow MRD negative on the day 14-21 of chemotherapy have the better OS and DFS.

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    Discussion on online and offline combined multidisciplinary team diagnosis-treatment mode for cancers
    Yang Guanghui, Wang Qian, Li Zheqi, Liu Chengxin, Sun Hongfu, Li Zhe, Zhang Haibo, Li Hongsheng, Li Baosheng
    2020, 47 (9):  542-545.  doi: 10.3760/cma.j.cn371439-20200612-00074
    Abstract ( 462 )   HTML ( 28 )   PDF (682KB) ( 249 )   Save

    Objective To discuss the feasibility of using online and offline combined multidisciplinary team (MDT) diagnosis-treatment mode in cancers diagnosis and treatment by comparing the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode. Methods A total of 168 esophageal cancer patients collected from March 17, 2020 to May 17, 2020 were took as the research objects in Shandong Cancer Hospital and Institute, through whom the consistency of the comprehensive diagnosis and treatment plans formulated by online and offline MDT diagnosis-treatment mode was evaluated. The clinical characteristics of patients with changed comprehensive diagnosis and treatment plans, such as age, Karnofsky performance status (KPS) score, whether combined with basic diseases, whether received anti-tumor treatment before and tumor location were analyzed, so as to explore the mechanism to improve the efficiency on the basis of quality assurance. Results The results showed that 86.3% (145/168) of the comprehensive diagnosis and treatment plans obtained by offline MDT diagnosis-treatment mode were consistent with online diagnosis-treatment MDT mode. Cases with inconsistent comprehensive diagnosis and treatment plans were characterized by elderly (> 69 years) (χ2=4.250, P=0.039), KPS score≥80 (χ2=15.520, P<0.001) and combined with underlying disease (χ2=7.135, P=0.008). Through further analysis, the changed cases were also characterized as with inadequate auxiliary examination or complex in imaging. Conclusion The online and offline combined MDT diagnosis-treatment mode is feasible. For the patients characterized of elderly (> 69 years old), KPS score ≥80, combined with underlying diseases, with incomplete auxiliary examination or complex in imaging, the offline MDT diagnosis-treatment mode should be adopted or supplemented.

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    Reviews
    Progress of Legumain in malignant tumors
    Yan Bingfang, Meng Wei, Bai Xuelian
    2020, 47 (9):  546-549.  doi: 10.3760/cma.j.cn371439-20200527-00075
    Abstract ( 670 )   HTML ( 38 )   PDF (628KB) ( 447 )   Save

    Legumain, also called asparaginyl endopeptidase, is one new member of the cysteine protease C13 family and plays various roles in human. In recent years, studies have displayed that Legumain is over expressed in a variety of tumors types and promotes the proliferation of tumor cells, tumor invasion and metastasis as well as angiogenesis through varied mechanisms. Further investigation of Legumain will be helpful to elucidate the pathogenesis and progression mechanism of malignant tumors and provide new molecular for targeted therapy of tumors.

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    Value of 3D-ASL, MRS and DTI in the diagnosis and treatment of radiation-induced temporal lobe injury of nasopharyngeal carcinoma
    Yang Minghui, Jin Feng
    2020, 47 (9):  550-554.  doi: 10.3760/cma.j.cn371439-20200603-00076
    Abstract ( 662 )   HTML ( 31 )   PDF (634KB) ( 349 )   Save

    Radiotherapy is the main treatment of nasopharyngeal carcinoma (NPC). With the continuous improvement of radiotherapy technology, the survival time of NPC patients is significantly improved, but the complications after radiotherapy have been paid more and more attention, in which the incidence of radiation-induced temporal lobe injury is higher, which seriously affects the quality of life of patients, and even reduces the survival rate. Therefore, it is particularly important to find a method for the examination of early radiation-induced temporal lobe injury. Three-dimensional arterial spin labeling (3D-ASL) analysis of cerebral blood flow (CBF) changes before and after radiotherapy, magnetic resonance spectroscopy (MRS) analysis to determine the changes of NAA/Cr, Cho/NAA, Cho/Cr ratio in the anterior and posterior temporal lobe before and after radiotherapy, and diffusion tensor imaging (DTI) to determine the changes of temporal lobe average diffusion coefficient (ADC) and anisotropy fraction (FA) before and after radiotherapy can help in the early diagnosis of radiation brain injury, especially through the combined use of the above three tests. It is expected to provide a feasible basis for the early diagnosis of radiation encephalopathy, and early nutritional neurotherapy is of great significance to improve the quality of life and survival rate of patients.

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    Radiogenomics in non-small cell lung cancer
    Yang Lei, Zhang Chuanyu, Zhang Zaixian, Liu Huan
    2020, 47 (9):  555-559.  doi: 10.3760/cma.j.cn371439-20200423-00077
    Abstract ( 504 )   HTML ( 22 )   PDF (637KB) ( 308 )   Save

    Radiogenomics explores the relationship between imaging features and gene expression patterns using radiomics, which is non-invasive and can present the overall information of tumors. The application of radiomics, somewhat effective in predicting gene mutations in non-small cell lung cancer (NSCLC), has recently become a research focus. Radiomic features, combined with conventional imaging, clinical and other features, can provide multi-directional information on tumors and play an increasingly important role in the prediction and precise treatment of NSCLC-driving gene phenotypes.

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    Application of immune checkpoint inhibitors in non-small cell lung cancer with EGFR mutant
    Xu Zexi, Zhang Huibo, Jin Yao, Peng Min
    2020, 47 (9):  560-564.  doi: 10.3760/cma.j.cn371439-20200209-00078
    Abstract ( 542 )   HTML ( 24 )   PDF (643KB) ( 366 )   Save

    Epidermal growth factor receptor (EGFR) gene is one of the most common driving genes in non-small cell lung cancer patients, and immune checkpoint inhibitors (ICIs) have been controversial in the clinical application of non-small cell lung cancer with EGFR mutant. The expression abundance of programmed death ligand 1 (PD-L1) is an important predictor to guide the application of ICIs, and EGFR mutations may affect PD-L1 expression in tumor cells. Recent clinical studies have pointed out that the single drug of ICIs is not effective in patients with EGFR mutation, however, the combination of ICIs combined with chemotherapy and the four drugs proposed in the IMpower150 trial show good clinical benefits. In addition, the safety of ICIs and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combination model needs to be further clarified.

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    Advance in comprehensive treatment of liver metastasis of gastric cancer
    Song Meijiao, Shen Qinglin, Zhang Xiquan, Yao Weirong
    2020, 47 (9):  565-568.  doi: 10.3760/cma.j.cn371439-20200629-00079
    Abstract ( 583 )   HTML ( 24 )   PDF (621KB) ( 412 )   Save

    Gastric cancer is one of the most common malignant tumors of digestive system, which has the characteristics of strong heterogeneity, rapid progress and poor prognosis. Liver metastasis of gastric cancer is the main cause of death of advanced gastric cancer. At present, the clinical treatment of gastric cancer mainly includes systematic treatment (systemic chemotherapy, targeted treatment, immunotherapy), surgical resection, interventional treatment and radiotherapy, but the therapeutic effects are not good, and liver metastasis of gastric cancer is lack of standardized treatment strategy. At present, the multi-disciplinary comprehensive treatment mode has been widely used in the diagnosis and treatment of malignant tumors, and has achieved good results. According to the clinical characteristics and surgical accessibility of liver metastasis of gastric cancer, the Chinese Gastrointestinal Surgery Expert Group divides it into three clinical types: resectable type, potential resectable type and non-resectable type. All kinds of clinical types of patients need multidisciplinary comprehensive treatment cooperation group experts to discuss and formulate individualized treatment plan.

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    Epigenetic pathogenesis of cutaneous squamous cell carcinoma
    Sang Yingbing, Liang Junqin
    2020, 47 (9):  569-572.  doi: 10.3760/cma.j.cn371439-20200123-00080
    Abstract ( 482 )   HTML ( 20 )   PDF (623KB) ( 233 )   Save

    Cutaneous squamous cell carcinoma (CSCC) is a kind of malignant tumor originated from keratinocytes within the epidermis and its appendages. Its etiology and pathogenesis are complex and unclear. The incidence of CSCC is increasing in the whole world, which makes the research on its pathogenesis increasing day by day. Epigenetics does not change genome sequence, but regulates gene expression by DNA methylation, histone modification, noncoding RNA, chromatin remodeling and so on. Its reversible and stable genetic characteristics will provide a new idea for the study of pathogenesis of CSCC.

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