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08 April 2023, Volume 50 Issue 4 Previous Issue    Next Issue

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Guidelines·Consensus

Chinese experts' consensus on the application of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy （2023 version） Radiation Oncology Treatment Physician Branch, Chinese Medical Doctor Association, Radiation Oncology Therapy Branch, Chinese Medical Association, Chinese Association of Radiation Therapy, China Anti-Cancer Association 2023, 50 (4):  193-201.  doi: 10.3760/cma.j.cn371439-20230227-00039 Abstract ( 168 )   HTML ( 26 )   PDF (959KB) ( 108 )   Save Neutropenia is the most common hematologic toxicity of concurrent chemoradiotherapy for malignant tumor patients， which can lead to follow-up treatment delay and/or dose reduction， induce febrile neutropenia and severe infection easily， thus affecting prognosis and safety of patients. It is important to prevent and manage neutropenia in patients with malignant tumors during concurrent chemoradiotherapy reasonably. As a long-acting preparation of recombinant human granulocyte colony-stimulating factor， pegylated recombinant human granulocyte colony-stimulating factor （PEG-rhG-CSF） can prevent and treat neutropenia， which is more convenient for clinical practice. In order to promote clinical rational administration of drugs， Radiation Oncology Treatment Physician Branch of Chinese Medical Doctor Association， Radiation Oncology Therapy Branch of Chinese Medical Association， Chinese Association of Radiation Therapy of China Anti-Cancer Association consulted guidelines and the latest evidence-based evidences related to PEG-rhG-CSF， evaluated the effectiveness and safety of the application of PEG-rhG-CSF during concurrent chemoradiotherapy， clarified the clinical pathway and administration route of prevention and treatment and then formed a Chinese experts' consensus on the application of PEG-rhG-CSF during concurrent chemoradiotherapy. Figures and Tables | References | Related Articles | Metrics

Original Articles

lncRNA FTX silencing inhibits gastric cancer cell proliferation through the miR-22-3p/NLRP3 inflammasome pathway Quan Zhenhao, Xu Feipeng, Huang Zhe, Huang Xianjin, Chen Rihong, Sun Kaiyu, Hu Xu, Lin Lin 2023, 50 (4):  202-207.  doi: 10.3760/cma.j.cn371439-20220429-00040 Abstract ( 112 )   HTML ( 15 )   PDF (1493KB) ( 77 )   Save Objective To investigate the regulatory effect of long non-coding RNA （lncRNA） FTX on gastric cancer cell proliferation through miR-22-3p/NOD-like receptor protein 3 （NLRP3） inflammasome pathway. Methods The gastric cancer cell line NCI-N87 were divided into blank control group， si-FTX-NC group， si-FTX group， si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group. Quantitative real-time fluorescent PCR was performed to analyze the expression levels of lncRNA FTX and miR-22-3p， clone formation assay was performed to analyze the proliferation ability of NCI-N87 cells， western blotting was performed to analyze the expressions of NLRP3 inflammasome pathway proteins， and dual-luciferase reporter assay was performed to analyze the targeting relationship between lncRNA FTX and miR-22-3p. Results The relative expressions of lncRNA FTX in the blank control group， si-FTX-NC group， si-FTX group， si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group were 1.03±0.09， 1.01±0.15， 0.42±0.08， 0.45±0.06 and 0.46±0.13 respectively， with a statistically significant difference （F=52.19， P<0.001）. The relative expressions of miR-22-3p were 1.04±0.12， 0.97±0.08， 2.26±0.15， 2.23±0.13 and 1.15±0.11 respectively， with a statistically significant difference （F=178.53， P<0.001）. Compared with the blank control group and si-FTX-NC group， the relative expressions of lncRNA FTX in the si-FTX group， si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased （all P<0.001）. Compared with the blank control group， si-FTX-NC group and si-FTX+miR-22-3p inhibitor group， the relative expressions of miR-22-3p in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group increased （all P<0.001）. The clones of the five groups were 115.50±7.25， 112.33±8.46， 54.83±5.17， 56.17±6.32 and 85.67±9.43， with a statistically significant difference （F=91.67， P<0.001）. The levels of NLRP3 protein in the five groups were 1.84±0.17， 1.86±0.12， 0.95±0.09， 0.97±0.11 and 1.28±0.19， with a statistically significant difference （F=60.62， P<0.001）. Compared with the blank control group and si-FTX-NC group， the number of clones and the level of NLRP3 protein of the si-FTX group， si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased （all P<0.05）. Compared with the si-FTX+miR-22-3p inhibitor group， the number of clones and the level of NLRP3 protein in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group decreased （all P<0.05）. The dual-luciferase reporter assay found that miR-22-3p was the target gene of lncRNA FTX. Conclusion Silencing the expression of lncRNA FTX can inhibit the proliferation of gastric cancer cells， and the mechanism may be related to the regulation of lncRNA FTX on the miR-22-3p/NLRP3 inflammasome pathway. Figures and Tables | References | Related Articles | Metrics

Value of CT radiomic features in differential diagnosis of lung metastases Xiong Min, Chen Yi, Wang Jianbo 2023, 50 (4):  208-213.  doi: 10.3760/cma.j.cn371439-20230120-00041 Abstract ( 121 )   HTML ( 16 )   PDF (1137KB) ( 49 )   Save Objective To distinguish lung metastases of different origin by constructing a classification model according to CT radiomics features. Methods A total of 226 patients with lung metastases of gastric cancer， breast cancer and kidney cancer attending Chongqing Red Cross Hospital from January 2015 to July 2020， with a total of 402 metastases， were randomly divided into a training cohort （training set， 136 patients， 280 metastases） and a validation cohort （validation set， 90 patients， 122 metastases） by the hold-out method. In addition， 68 patients with lung metastases （138 lung metastases in total） attending Chongqing Red Cross Hospital from August 2020 to April 2022 were matched as an external test cohort （test set）. Region of interest segmentation was performed by two experienced radiologists independently and manually without clinical information to construct the model by using LASSO screening for the best radiomic features. Support vector machine （SVM） and random forest （RF） were selected to build dichotomous and trichotomous models respectively. The receiver operating characteristic curve was used to evaluate the classification efficiency of both models. Results There were no statistically significant differences in age （t=-0.06， P=0.534）， gender （χ2<0.01， P=0.961） and number of lung metastases （χ2=0.71， P=0.703） between the validation and test sets. A total of 792 radiomic features were extracted， 703 of which had good agreement （intraclass correlation coefficient≥0.75）， while 89 features being excluded for having poor agreement （intraclass correlation coefficient<0.75）. The dichotomous model （SVM） screened 28 （lung metastases from gastric cancer vs. lung metastases from breast cancer）， 25 （lung metastases from gastric cancer vs. lung metastases from kidney cancer） and 34 （lung metastases from kidney cancer vs. lung metastases from breast cancer） features， respectively； the trichotomous model （RF） screened 20 features （three types of lung metastases）， in which Short Run Emphasis and Inverse Variance were significantly higher in lung metastases from kidney cancer than in the other two types， correlation was higher in lung metastases from gastric cancer than in the other two types， and there was no significant difference in the sphericity of the three lung metastases. For the dichotomous model， in the validation set， the area under the curve （AUC） of the 28 features selected to distinguish gastric cancer lung metastases from breast cancer lung metastases was 0.81， the AUC of the 25 features distinguishing gastric cancer lung metastases from kidney cancer lung metastases was 0.86， and the AUC of the 34 features distinguishing kidney cancer lung metastases from breast cancer lung metastases was 0.92， and the AUCs of the test set were 0.80， 0.79 and 0.86 respectively. For the trichotomous model， the AUC for predicting lung metastases from gastric cancer， breast cancer and kidney cancer in the validation set were 0.85， 0.82 and 0.91 respectively， and both macroscopic and microscopic AUC were 0.85； In the test set， the AUC for predicting lung metastases from gastric cancer， breast cancer， and kidney cancer were 0.77， 0.86 and 0.84 respectively， and both macroscopic and microscopic AUC were 0.81. Conclusion The SVM and RF models based on CT radiomic features are helpful in distinguishing lung metastases derived from gastric cancer， breast cancer and kidney cancer. Figures and Tables | References | Related Articles | Metrics

Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance Li Jun, Xue Sheng, Wang Weijie, Tao Run, Zhang Jiajun 2023, 50 (4):  214-219.  doi: 10.3760/cma.j.cn371439-20230113-00042 Abstract ( 130 )   HTML ( 47 )   PDF (2510KB) ( 48 )   Save Objective To analyze the expression of targeting protein for Xklp2 （TPX2） in kidney renal clear cell carcinoma （KIRC） and its clinical significance. Methods The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology， the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database， which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage， molecular subtypes， lymph node metastasis， and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins， and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database. Results Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% （26/54） in cancer tissues， which was higher than that in paracancerous tissues （20.37%，11/54） （χ2=9.25， P=0.002）. The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 （1.49， 2.42）， normal tissue: 0.35 （0.24， 0.57）， U=2 297.00， P<0.001]. The expression of TPX2 mRNA was related to the clinical stage （χ2=34.36， P<0.001）， molecular subtypes （χ2=30.15， P<0.001）， and lymph node metastasis status （χ2=27.21， P<0.001） of KIRC patients. The 5-year survival rate （53.80%） in patients with high TPX2 expression was lower than that in patients with low TPX2 expression （74.40%， χ2=18.87， P<0.001）. STRING database protein interaction network construction obtained 20 TPX2-related proteins， and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells （r=0.30， P<0.001）， CD8+ T cells （r=0.23， P<0.001）， CD4+ T cells （r=0.18， P<0.001）， macrophages （r=0.20， P<0.001）， neutrophils （r=0.31， P<0.001）， dendritic cells （r=0.39， P<0.001） infiltration and most of its biomarkers （all P<0.05）. It was positively correlated with immune checkpoint PD-1 （r=0.31， P<0.001） and CTLA-4 （r=0.27， P<0.001）， but not correlated with PD-L1 （r=0.07， P=0.146）. Conclusion TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC. Figures and Tables | References | Related Articles | Metrics

Construction of machine learning models for predicting the risk of postoperative distant metastasis recurrence in serous ovarian cancer Yang Lirong, Wang Yufeng 2023, 50 (4):  220-226.  doi: 10.3760/cma.j.cn371439-20221214-00043 Abstract ( 105 )   HTML ( 14 )   PDF (1117KB) ( 53 )   Save Objective To develop a machine model to predict the risk of postoperative distant metastasis recurrence in serous ovarian cancer （SOC） based on routine clinical data. Methods Participants included 687 patients with recurrent SOC who underwent surgery at Yunnan Cancer Hospital from January 2010 to December 2020. According to the recurrence status， the patients were divided into the distant metastasis group （n=105） and the non-distant metastasis group （n=582）. Logistic regression was used to screen the variables related to distant metastasis of SOC. Based on these selected variables， five machine learning methods including K-nearest neighbor （KNN）， logistic regression （LR）， random forest （RF）， support vector machine （SVM） and extreme gradient boosting （XGBoost） were used to develop the postoperative distant metastasis risk prediction model of SOC. For model validation， the 10-fold cross-validation method was used for internal validation. The performance of the models was evaluated using the receiver operating characteristic curve. Results There were statistically significant differences in International Federation of Gynecology and Obstetrics （FIGO） stage （Z=-3.81， P<0.001）， perioperative chemotherapy cycle （t=-5.11， P<0.001）， lymph node metastasis （χ2=5.98， P=0.014）， peritoneal effusion cytology （Z=-2.22， P=0.026）， and neoadjuvant chemotherapy （χ2=5.29， P=0.021） between patients in the distant metastasis group and the non-distant metastasis group. Multivariate regression analysis showed that the FIGO stage （OR=1.54， 95%CI： 1.07-2.22， P=0.019） and perioperative chemotherapy cycle （OR=1.22， 95%CI： 0.09-0.36， P<0.001） were independent influencing factors for postoperative distant metastasis recurrence in SOC. Peritoneal effusion cytology （OR=1.20， 95%CI： 0.71-1.89， P=0.180） was not an independent influencing factor for distant metastasis of SOC. It was ultimately included in the construction of the model， for its inclusion could improve the area under the curve （AUC） of the model. Among the five machine learning models constructed based on the above three variables， the KNN-based model had the best performance in identifying distant metastasis of SOC， with the AUC of 0.750， sensitivity of 0.591， specificity of 0.786， and accuracy of 85.0%. The AUC of the LR model was 0.679， the sensitivity was 0.545， the specificity was 0.765， and the accuracy was 84.3%. The AUC of SVM model was 0.634， the sensitivity was 0.240， the specificity was 0.968， and the accuracy was 84.7%. The AUC of RF model was 0.575， the sensitivity was 0.905， the specificity was 0.245， and the accuracy was 84.7%. The AUC of XGBoost model was 0.704， the sensitivity was 0.567， the specificity was 0.745， and the accuracy was 84.9%. Conclusion FIGO stage and perioperative chemotherapy cycle are independent influencing factors for postoperative distant metastasis recurrence in SOC. The KNN model established based on FIGO stage， perioperative chemotherapy cycle and peritoneal effusion cytology has high discrimination degree and accuracy rate in predicting postoperative distant metastasis recurrence of SOC. Figures and Tables | References | Related Articles | Metrics

Reviews

Research progress of cancer-associated fibroblasts in tumor radiotherapy resistance Xu Meng, Jiang Wei, Zhu Haitao, Cao Xiongfeng 2023, 50 (4):  227-230.  doi: 10.3760/cma.j.cn371439-20230105-00044 Abstract ( 171 )   HTML ( 11 )   PDF (737KB) ( 71 )   Save Cancer-associated fibroblasts （CAFs） is considered as a key factor for the severely limited efficacy in tumor radiotherapy. CAFs， as the primary stromal cells in the tumor microenvironment， can lead to tumor radiotherapy resistance by secreting a series of pro-tumor cytokines and nutrients， inhibiting anti-tumor immune response and remodeling extracellular matrix. Some progress has been made in the study of targeted CAFs sensitization radiotherapy，but the relevant study system is still imperfect. Therefore， a systematic exploration of the role of CAFs in tumor radiotherapy resistance and CAFs targeted therapy strategies can provide a basis for improving the current status of tumor radiotherapy resistance. References | Related Articles | Metrics

Research progress of CAR-T in the treatment of esophageal squamous cell carcinoma Ding Hao, Ying Jintao, Fu Maoyong 2023, 50 (4):  231-235.  doi: 10.3760/cma.j.cn371439-20221123-00045 Abstract ( 148 )   HTML ( 20 )   PDF (752KB) ( 86 )   Save Chimeric antigen receptor T cell （CAR-T） therapy， an emerging immunotherapy， has achieved remarkable results in the treatment of hematologic tumors. However， it's limited in the treatment of solid tumors such as esophageal squamous cell carcinoma due to various factors. Clarifying the reasons for the limitation of CAR-T therapy and exploring the corresponding solutions can provide new ideas and insights for the treatment of esophageal squamous cell carcinoma. Figures and Tables | References | Related Articles | Metrics

Research progress on targeted therapy of breast cancer with low expression of HER2 Zhu Jun, Huang Meijin, Li Yuan, Liu Zegang, Xun Xin, Chen Hong 2023, 50 (4):  236-240.  doi: 10.3760/cma.j.cn371439-20221230-00046 Abstract ( 120 )   HTML ( 15 )   PDF (721KB) ( 80 )   Save Breast cancer has become the malignant tumor with the highest incidence rate among women， of which human epidermal growth factor receptor 2 （HER2） positive breast cancer accounts for about 15%-20%. With the development of anti HER2 targeted drugs， the survival and prognosis of HER2 positive breast cancer has significantly benefited. About 45%-55% of breast cancer patients have low HER2 expression， and these patients usually do not receive anti HER2 treatment. However， there is a significant difference between the biological behavior and prognosis of breast cancer with low HER2 expression and breast cancer with zero HER2 expression. It is helpful to differentiate and adopt corresponding treatment strategies to improve the prognosis of patients. At present， there have been many advances in targeted therapy of breast cancer with low HER2 expression， which provides a useful reference for precision treatment of breast cancer with low HER2 expression. References | Related Articles | Metrics

Mechanism of action of glucocorticoid receptors in the growth of hepatoma cells Li Jiaxuan, Feng Yinglu 2023, 50 (4):  241-243.  doi: 10.3760/cma.j.cn371439-20230120-00047 Abstract ( 114 )   HTML ( 6 )   PDF (685KB) ( 49 )   Save The glucocorticoid receptor （GR） plays a critical role in signal transduction， expression of related genes and apoptosis of cancer cells. Hepatocellular carcinoma is characterized by high aggressiveness and mortality. In the exploration of the relationship between GR and hepatocellular carcinoma， numerous studies have shown that GR has an inhibitory effect on the growth of hepatocellular carcinoma cells， which provides new ideas and methods for the clinical application of GR in the treatment of hepatocellular carcinoma. References | Related Articles | Metrics

Research progress on the interaction between gut microbiota and radiation enteritis Shi Xaioqi, Wang Hongyan 2023, 50 (4):  244-247.  doi: 10.3760/cma.j.cn371439-20230208-00048 Abstract ( 100 )   HTML ( 12 )   PDF (700KB) ( 35 )   Save Radiotherapy is an important treatment for abdominal and pelvic tumors， but it has a high incidence of the adverse reaction radiation enteritis. Abdominal and pelvic radiotherapy can induce apoptosis of intestinal crypt cells， destroy the intestinal barrier and change the composition of gut microbiota. Dysbiosis of gut microbiota can aggravate radiation enteritis. Fecal flora transplantation， as well as the use of probiotics， prebiotics and antibiotics can regulate gut microbiota， which is an effective method to prevent and treat radiation enteritis. References | Related Articles | Metrics

Progress in imaging evaluation of lateral lymph node metastasis in rectal cancer Zeng Liwu, Du Yuqiang, Zhang Peng, Tao Kaixiong 2023, 50 (4):  248-251.  doi: 10.3760/cma.j.cn371439-20230217-00049 Abstract ( 97 )   HTML ( 8 )   PDF (706KB) ( 37 )   Save Lateral drainage is an important way for the middle and lower rectum. There are still disputes between Eastern and Western scholars regarding the treatment strategy of lateral lymph node metastasis. It is difficult to diagnose lateral lymph node metastasis by pathologic examination before surgery. MRI is the main method for diagnosis of lateral lymph node metastasis in rectal cancer. The diagnostic criteria for patients before and after neoadjuvant treatment are slightly different. CT， PET/CT and radiomics also have certain advantages in the diagnosis of lateral lymph node metastasis. If necessary， the combination of multiple methods can help in the diagnosis of lateral lymph node metastasis. References | Related Articles | Metrics