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08 June 2023, Volume 50 Issue 6 Previous Issue    Next Issue

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Original Articles

Predictive value of inflammatory markers of peripheral blood cells on prognosis in the advanced non-small cell lung cancer with immune therapy He Guangsi, Wang Jun, Feng Mengmeng 2023, 50 (6):  321-327.  doi: 10.3760/cma.j.cn371439-20230404-00065 Abstract ( 178 )   HTML ( 36 )   PDF (870KB) ( 104 )   Save Objective To explore the predictive value of neutrophil to lymphocyte ratio （NLR） and systemic immune-inflammation index （SII） of inflammatory markers of peripheral blood cells on the prognosis in the advanced non-small cell lung cancer （NSCLC） patients with immune therapy. Methods The hematologic and clinical data of 58 patients with advanced non-small cell lung cancer who received the treatment of immune therapy in the First People's Hospital of Chuzhou of Anhui Province from January 2018 to June 2022 were retrospectively analyzed. X-tile software was used to calculate the optimal cut-off values of NLR and SII. All patients were divided into high and low groups according to the optimal cut-off values. The relationship between different NLR，SII and clinicopathological features，clinical efficacy，prognosis of the advanced non-small cell lung cancer patients with immune therapy were analyzed. Cox regression models were used to perform univariate and multivariate analyses of factors affecting patient prognosis. Results The optimal cut-off values for NLR and SII were 3.2 and 546.5，respectively. There were statistically significant differences in regional lymph node metastasis （χ2=5.03，P=0.025） and the number of metastatic sites （χ2=11.60，P=0.001） between patients in the low-NLR group （NLR<3.2，n=26） and the high-NLR group （NLR≥3.2，n=32）. There were statistically significant differences in location of the primary site （χ2=8.34，P=0.004） between patients in the low-SII group （SII<546.5，n=28） and the high-SII group （SII≥546.5，n=30）. The objective response rate （ORR） of the low-NLR group [50.00%（13/26）] was higher than that of the high-NLR group [21.88%（7/32）]，and there was a statistically significant difference （χ2=5.02，P=0.025）； the disease control rate （DCR） of the low-NLR group [69.23%（18/26）] was higher than that of the high-NLR group [50.00%（16/32）]，but there was no statistically significant difference （χ2=2.19，P=0.139）. The ORR of the low-SII group [53.57%（15/28）] was higher than that of the high-SII group [26.67%（8/30）]； The DCR of the low-SII group [67.86%（19/28）] was higher than that of the high-SII group [33.33%（10/30）]，and there were statistically significant differences （χ2=4.38，P=0.036； χ2=6.91，P=0.009）. The median overall survival （OS） of patients in the low-NLR group （17.6 months） was longer than that of the high-NLR group （11.7 months），and there was a statistically significant difference （χ2=11.07，P=0.001）. The median OS of patients in the low-SII group （16.5 months） was longer than that of the high-SII group （12.3 months），and there was a statistically significant difference （χ2=5.53，P=0.019）. Univariate analysis showed that Eastern Cooperative Oncology Group （ECOG） score （HR=2.20，95%CI：1.10-4.39，P=0.025），brain metastases （HR=3.24，95%CI：1.61-6.50，P=0.001），the number of transferred sites （HR=2.83，95%CI：1.44-5.57，P=0.003），NLR （HR=3.22，95%CI：1.56-6.66，P=0.002） and SII （HR=2.18，95%CI：1.12-4.24，P=0.021） were all independent influence factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy； multivariate analysis showed that brain metastases （HR=2.91，95%CI：1.22-6.94，P=0.016），NLR （HR=2.88，95%CI：1.17-7.13，P=0.022） and SII （HR=3.63，95%CI：1.40-9.39，P=0.008） were all independent risk factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy. Conclusion NLR and SII can be used as important indicators for predicting the efficacy of immunotherapy in the advanced NSCLC and elevated NLR and SII can indicate poor prognosis of patients. Figures and Tables | References | Related Articles | Metrics

Analysis of circRNA in esophageal squamous cell carcinoma based on high-throughput sequencing data Cui Manli, Lu Ning, Zhu Lin, Li Qian, Zhang Mingxin 2023, 50 (6):  328-335.  doi: 10.3760/cma.j.cn371439-20230308-00066 Abstract ( 141 )   HTML ( 12 )   PDF (3609KB) ( 74 )   Save Objective To analyze circRNAs specifically differentially expressed in esophageal squamous cell carcinoma （ESCC） based on high-throughput sequencing data. Methods Six patients with pathologically confirmed ESCC in Tangdu Hospital of Air Force Medical University from March 2018 to March 2019 were selected as the research subjects，among which 3 were stage Ⅰ ESCC and 3 were stage Ⅲ ESCC. High-throughput sequencing technology was used to analyze the difference in the expression of circRNA in cancer tissues and adjacent tissues of patients. GO enrichment analysis，KEGG enrichment analysis and Venn analysis were performed on differentially expressed genes. The circRNA-miRNA-mRNA network was constructed using Cytoscape software. The most significantly differentially expressed genes in cancer tissues were verified in cells and tissues，and the relationships between circRNAs and clinical pathological indicators of patients were analyzed. Results A total of 553 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅰ ESCC patients，of which 413 were up-regulated and 140 were down-regulated in cancer tissues； A total of 425 differentially expressed circRNAs were screened in paracancerous tissues and cancer tissues of 3 stage Ⅲ ESCC patients，of which 276 were up-regulated and 149 were down-regulated in cancer tissues. GO enrichment analysis showed that the host genes of differential circRNAs in patients with stage Ⅰ ESCC were mainly enriched in cell cycle-related biological processes such as mitotic G2/M transition. The host genes of differential circRNAs in patients with stage Ⅲ ESCC were mainly enriched in biological processes related to cell division and tumor development，such as mitotic spindle checkpoint and cell matrix adhesion. KEGG enrichment analysis showed that the differential circRNAs in cancer tissues of stage Ⅰ and stage Ⅲ ESCC patients were mainly enriched in cancer-related biological pathways such as cell adhesion. The results of Venn analysis showed that in stage Ⅰ ESCC patients and stage Ⅲ ESCC patients，2 and 8 circRNAs that were only specifically expressed in paracancerous tissues and had significant differences were screened out respectively，and were only specifically expressed in cancer tissues with significant differences were 11 and 14 respectively. The circRNA-miRNA-mRNA network showed that the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅰ ESCC patients consisted of 7 circRNA nodes，10 miRNA nodes and 28 mRNA nodes，and the cancer tissue-related circRNA-miRNA-mRNA network in stage Ⅲ ESCC patients consisted of 7 circRNA nodes，9 miRNA nodes and 49 mRNA nodes. The most significantly differentially expressed hsa-circ-0060927 and hsa-circ-0109301 in cancer tissues of patients with stage Ⅰ ESCC and stage Ⅲ ESCC were selected for cytological and histological verification. The results showed that the relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1，TE13，KYSE30，KYSE170，and human normal esophageal epithelial cell line HEEC were 7.82±1.96，12.69±2.68，12.78±2.74，7.53±1.75，and 2.43±0.17，respectively，with a statistically significant difference （F=4.68，P=0.004）. The relative expression levels of hsa-circ-0060927 in ESCC cell lines TE1，TE13，KYSE30，and KYSE170 were higher than that in human normal esophageal epithelial cell line HEEC，with statistically significant differences （P=0.009； P=0.003； P=0.003； P=0.007）. The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1，TE13，KYSE30，KYSE170，and human normal esophageal epithelial cell line HEEC were 5.16±1.32，6.28±1.57，4.89±1.13，8.92±2.12，and 22.56±4.13，respectively，with a statistically significant difference （F=4.31，P=0.022）. The relative expression levels of hsa-circ-0109301 in ESCC cell lines TE1，TE13，KYSE30，and KYSE170 were lower than that in human normal esophageal epithelial cell line HEEC，with statistically significant differences （P=0.027； P=0.015； P=0.024； P=0.008）. The expression level of hsa-circ-0060927 in cancer tissues of 13 early ESCC patients was 12.89±2.67，significantly higher than 5.73±1.18 in paracancerous tissue，and there was a statistically significant difference （t=15.02，P<0.001）； the expression level of hsa-circ-0109301 in cancer tissues of 19 patients with advanced ESCC was 7.78±2.17，significantly lower than 16.32±3.15 in paracancerous tissue，and there was a statistically significant difference （t=9.73，P<0.001）. The expression of hsa-circ-0109301 was related to the degree of tumor differentiation in advanced ESCC patients （P=0.023）. Conclusion One circRNA （hsa-circ-0060927 and hsa-circ-0109301） with the most significanty differential expression is selected in early and advanced ESCC patients respectively，in which hsa-circ-0060927 is highly expressed in ESCC cancer tissues and hsa-circ-0109301 is lowly expressed in ESCC cancer tissues，and the expression of hsa-circ-0109301 is correlated with the degree of tumor differentiation. 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Level of serum FABP1 and its relationship with Helicobacter pylori infection in patients with gastric cancer Zhu Siyu, Wang Xuehong, Li Wenqian, Liu Shu 2023, 50 (6):  336-341.  doi: 10.3760/cma.j.cn371439-20230214-00067 Abstract ( 115 )   HTML ( 15 )   PDF (837KB) ( 60 )   Save Objective To investigate the serum level of fatty acid binding protein 1 （FABP1） and its relationship with Helicobacter pylori （Hp） infection in patients with gastric cancer. Methods Forty gastric cancer patients （gastric cancer group） who were hospitalized in Affiliated Hospital of Qinghai University from August 2021 to August 2022 were selected as the research subjects，and 40 physical examination subjects during the same period were selected as the normal control group and 40 chronic atrophic gastritis patients were selected as the CAG group. The Hp infection were detected by 13C breath test，and the levels of serum FABP1 were detected by enzyme-linked immunosorbent assay. The Hp infection status，serum FABP1 levels，and the relationship between the two in the three groups of study subjects were analyzed. And the relationships between the level of serum FABP1 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value of serum FABP1，CA19-9，CA72-4 and combined test of 3 indexes were evaluated by receiver operating characteristic （ROC） curve. Results The Hp infection rates in the control group，CAG group，and gastric cancer group were 32.50% （13/40），55.00% （22/40），and 60.00% （24/40），respectively，with a statistically significant difference （χ2=6.87，P=0.032）. Among them，the Hp infection rate in the control group was compared with that in the gastric cancer group，with a statistically significant difference （P<0.05），and there were no statistically significant differences between the CAG group and the control group，the gastric cancer group （both P>0.05）. The levels of serum FABP1 in the control group，CAG group，and gastric cancer group were [63.47 （37.53，71.59）] ng/ml，[65.26 （51.15，79.67）] ng/ml，and [72.84 （53.44，82.25）] ng/ml，respectively，with a statistically significant difference （H=6.62，P=0.037）. Among them，there was a statistically significant difference between the control group and the gastric cancer group （H=19.93，P=0.031），while there were no statistically significant differences between the CAG group and the control group，the gastric cancer group （H=1.50，P=0.133； H=1.09，P=0.277）. Among all study subjects，the levels of serum FABP1 in the Hp positive group （n=59） and Hp negative group （n=61） were [77.05 （68.90，83.54）] ng/ml and [47.80 （37.76，63.32）] ng/ml，respectively，with a statistically significant difference （Z=7.45，P<0.001）. In the control group，the levels of FABP1 in the serum of Hp positive and Hp negative persons were [77.34 （68.84，86.31）] ng/ml and [39.79 （36.83，63.75）] ng/ml，respectively，with a statistically significant difference （Z=4.46，P<0.001）. In the CAG group，the levels of FABP1 in the serum of Hp positive and Hp negative patients were [76.51 （65.30，80.97）] ng/ml and [49.34 （39.92，59.41）] ng/ml，respectively，with a statistically significant difference （Z=4.32，P<0.001）. In the gastric cancer group，the levels of FABP1 in the serum of Hp positive and Hp negative patients were [77.15 （72.62，84.13）] ng/ml and [50.57 （44.54，68.97）] ng/ml，respectively，with a statistically significant difference （Z=4.32，P<0.001）. There were significant correlations between the serum level of FABP1 and smoking （t=2.54，P=0.015），tumor diameter （t=2.23，P=0.035），and lymph node metastasis （t=3.22，P=0.003） in gastric cancer patients. And there were no significant correlations between FABP1 and gender （t=0.98，P=0.333），age （t=1.60，P=0.117），alcohol consumption （Z=0.10，P=0.925），tumor site （F=1.06，P=0.356），degree of differentiation （t=0.61，P=0.545），the depth of infiltration （t=1.41，P=0.166），distant metastasis （Z=1.96，P=0.050） and TNM staging （Z=0.66，P=0.508）. ROC curve analysis showed that the area under the curve （AUC） of serum FABP1 for gastric cancer diagnosis was 0.62，95%CI：0.51-0.72，the sensitivity and specificity were 57.50% and 68.70%，respectively； the AUC of CA19-9 for gastric cancer diagnosis was 0.89，95%CI：0.83-0.95，the sensitivity and specificity were 77.50%，86.30%，respectively； the AUC of CA72-4 for gastric cancer diagnosis was 0.88，95%CI：0.81-0.94，the sensitivity and specificity were 70.00%，93.70%，respectively； the AUC of combined test of 3 indexes for gastric cancer diagnosis was 0.91，95%CI：0.82-0.97，the sensitivity and specificity were 67.50% and 95.00%，respectively. Conclusion The Hp infection rate of gastric cancer patients is higher than that of the health examiners，the serum FABP1 level of gastric cancer patients is higher than that of the healthy health examiners，the serum FABP1 level of Hp positive persons is higher than that of Hp negative persons，and Hp infection and FABP1 level may have a common carcinogenic mechanism in the occurrence and development of gastric cancer. Figures and Tables | References | Related Articles | Metrics

Prognosis and influencing factors of platinum sensitive recurrent ovarian cancer treated by secondary cytoreduction surgery in patients with unsatisfactory primary cytoreduction surgery Li Chenxi, Zhao Hongwei 2023, 50 (6):  342-347.  doi: 10.3760/cma.j.cn371439-20230116-00068 Abstract ( 97 )   HTML ( 18 )   PDF (845KB) ( 48 )   Save Objective To investigate the prognosis and influencing factors of secondary cytoreduction surgery （SCS） in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Methods The clinical and follow-up data of 116 patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery and received the first diagnosis and operation in Shanxi Provincial Cancer Hospital from January 2005 to December 2018 were retrospectively analyzed. Among them，33 patients received SCS+chemotherapy and 83 patients received chemotherapy alone. In order to eliminate the component differences in general clinical data between the two groups，28 pairs total 56 patients were selected from each group to form a matching cohort by propensity score matching，and their data were analyzed. The main outcome measures were progression-free survival （PFS） and overall survival （OS）. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors of patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Results The median PFS of 56 matched patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery was 9.0 months. The 0.5- and 1-year PFS rates were 67.9% and 25.0% respectively. The median OS of 56 patients was 57.5 months. The 3- and 5-year OS rates were 60.7% and 39.3% respectively. The median PFS was 10.5 months in the SCS+chemotherapy patients and 7.5 months in the chemotherapy alone patients，and the 0.5- and 1-year PFS rates were 82.1% vs. 57.1% and 32.1% vs. 21.4% respectively，with a statistically significant difference （χ2=3.88，P=0.049）. The median OS was 70.0 months in the SCS+chemotherapy patients，and 60.0 months in the chemotherapy alone patients，and the 3- and 5-year OS rates of the SCS+chemotherapy patients and chemotherapy alone patients were 88.5% vs. 64.3% and 70.0% vs. 53.0%，with no statistically significant difference （χ2=3.63，P=0.057）. Univariate analysis showed that International Federation of Gynecology and Obstetrics （FIGO） staging （HR=3.17，95%CI：1.32-7.59，P=0.010） and treatment-free interval from the last platinum （TFIp）（HR=0.35，95%CI：0.18-0.68，P=0.002） were independent influencing factors of PFS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Carbohydrate antigen 125 （HR=2.46，95%CI：1.21-5.00，P=0.013） was an independent influencing factor of OS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Multivariate analysis showed that FIGO staging （HR=2.95，95%CI：1.18-7.36，P=0.020） and TFIp （HR=0.33，95%CI：0.16-0.66，P=0.002） were independent prognostic factors of PFS. Conclusion For platinum-sensitive recurrent ovarian cancer patients who do not achieve satisfactory tumor reduction after primary cytoreduction surgery，but achieve clinical complete response after postoperative chemotherapy，SCS may prolong their PFS after treatment，and OS also shows a beneficial trend after treatment，but with no statistically significant difference. FIGO staging at initial treatment and TFIp before the first relapse are independent prognostic factors of PFS in patients with platinum-sensitive recurrent ovarian cancer whose tumor reduction with unsatisfactory primary cytoreduction surgery. Figures and Tables | References | Related Articles | Metrics

Reviews

Role of ANGPTL4 in tumorigenesis and development Liu Yanying, Yang Yu 2023, 50 (6):  348-351.  doi: 10.3760/cma.j.cn371439-20221218-00069 Abstract ( 128 )   HTML ( 5 )   PDF (669KB) ( 57 )   Save Angiopoietin-like protein 4 （ANGPTL4） is involved in the regulation of glucose and lipid metabolism and angiogenesis，and is closely related to tumorigenesis，development，invasion and metastasis. The abnormal expression of ANGPTL4 gene can promote or inhibit the growth and proliferation of tumor cells and play a tumor-promoting or anti-tumor role in the occurrence and development of tumors. To explore the role of ANGPTL4 gene in the occurrence and development of different tumors can provide reference for evaluating the diagnosis，prognosis and curative effect of tumors. References | Related Articles | Metrics

Research progress on the mechanism of endocrine therapy resistance for breast cancer Wang Wende, Zeng De 2023, 50 (6):  352-356.  doi: 10.3760/cma.j.cn371439-20221123-00070 Abstract ( 168 )   HTML ( 15 )   PDF (689KB) ( 109 )   Save Endocrine therapy resistance is a major challenge in the treatment of hormone receptor-positive breast cancer. In recent years，endocrine resistance mechanisms have focused on ESR1 mutations or fusions，epigenetic regulation，abnormal regulation of signal transduction pathway，cell cycle regulation，cancer stem cells，metabolic reprogramming，tumor microenvironment and autophagy. Exploring the latest advances in the mechanisms of endocrine therapy resistance in breast cancer may provide more research ideas and treatment options for the precision treatment of hormone receptor-positive breast cancer. References | Related Articles | Metrics

Advances in the treatment of extramammary Paget disease Cheng Juan, Chen Hong 2023, 50 (6):  357-361.  doi: 10.3760/cma.j.cn371439-20230322-00071 Abstract ( 119 )   HTML ( 6 )   PDF (687KB) ( 66 )   Save Extramammary Paget disease （EMPD） is a kind of rare clinical malignant tumor in the skin. Surgical treatment is the main treatment method，and the Mohs microsurgery is considered the first choice which can control the incision margin accurately and reduce the recurrence rate. Due to the insidious and multifocal nature of the disease，the postoperative recurrence rate is still high. The other treatment methods include radiation therapy，chemotherapy，targeted therapy，photodynamic therapy，local drug therapy and laser therapy. Further research on the progress of EMPD treatment is helpful for the management and treatment of patients in clinical practice. References | Related Articles | Metrics

Research progress on the application of combining radiotherapy and systemic therapy in breast cancer Li Qingshan, Xie Xin, Zhang Nan, Liu Shuai 2023, 50 (6):  362-367.  doi: 10.3760/cma.j.cn371439-20230404-00072 Abstract ( 126 )   HTML ( 9 )   PDF (702KB) ( 80 )   Save Compared with single therapy，radiotherapy combined with chemotherapy，endocrine therapy，molecular targeted therapy and immunological therapy can not only shorten the treatment cycle，but also improve the local control rate and prolong the survival of patients. However，the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore，exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits. References | Related Articles | Metrics

Progress of PARP inhibitors in targeted therapy of small cell lung cancer Liu Li, Zhu Siqi, Sun Mengying, He Jingdong 2023, 50 (6):  368-372.  doi: 10.3760/cma.j.cn371439-20221123-00073 Abstract ( 148 )   HTML ( 6 )   PDF (689KB) ( 77 )   Save Small cell lung cancer （SCLC） is a rapidly developing malignant tumor，which is highly heterogeneous and prone to drug resistance，and the prognosis is usually poor. Poly ADP-ribose polymerase （PARP） inhibitors target the DNA damage response pathway，preventing DNA repair，thereby exerting anti-tumor effects. Currently，PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited，it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC. References | Related Articles | Metrics

Gut flora and cervical cancer Lyu Lu, Sun Pengfei 2023, 50 (6):  373-376.  doi: 10.3760/cma.j.cn371439-20230410-00074 Abstract ( 118 )   HTML ( 18 )   PDF (664KB) ( 59 )   Save The occurrence and progression of cervical cancer are influenced by gut flora. Patients with cervical cancer have different gut flora from healthy women，and the detection and evaluation of gut flora can help in the diagnosis，immunotherapy，assessment of radiotherapy efficacy and prognosis prediction of cervical cancer. Regulation of gut flora is of great clinical value in enhancing response to anti-tumor therapy，improving patients' quality of life and improving prognosis. References | Related Articles | Metrics

Research progress of cytokine release syndrome related to CAR-T immunotherapy Zhang Li, Xiang Zhuo, Wang Qiang, Bi Jingwang 2023, 50 (6):  377-381.  doi: 10.3760/cma.j.cn371439-20221203-00075 Abstract ( 140 )   HTML ( 7 )   PDF (722KB) ( 76 )   Save Chimeric antigen receptor T-cell （CAR-T） immunotherapy is one of the new models of tumor targeted therapy. However，the presence of cytokine release syndrome （CRS） after CAR-T infusion is a key obstacle limiting its therapeutic effects. Macrophage activation and pyrosis of target tumor cells can trigger the release of interleukin-6 and other inflammatory factors，and excessive inflammatory factors can lead to excessive activation of endothelial cells，which is a key molecular mechanism for the escalation of CRS and the occurrence of serious adverse events. Intervention in multiple stages of cytokine production and structural optimization of chimeric antigen receptor molecules are effective strategies to reduce CRS. References | Related Articles | Metrics