Table of Content

20 February 2024, Volume 24 Issue 01

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Original Articles and Clinical Research

mFOLFOX7 venous chemotherapy plus camrelizumab and apatinib for hepatocellular carcinoma in CNLC stage Ⅲ （VIC-TRIPLET）： a prospective study

PENG Lin-hui, CHEN Tao, XU Yun-xiu-xiu, WANG Jie, CHEN Jie, LI Yong, HUANG Pin-bo, ZHONG Guo-ping, CHEN Qian, YE Cong-ting, CHEN Ya-jin

2024, 24(01):  1-6.  DOI: 10.3969/j.issn.1009-976X.2024.01.001

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Objective The combination of anti-angiogenesis and immune checkpoint blockade showed promising outcomes for advanced HCC. Hepatic artery infusion chemotherapy （HAIC） combined with apatinib and camrelizumab could augment treatment efficacy in preliminary study. But HAIC had disadvantages such as technical limitations, expensive cost and poor patient comfort. In the present study, we aimed to investigate the efficacy and safety of Venous Infusion Chemotherapy（VIC） plus camrelizumab and apatinib for CNLC stage Ⅲ HCC. Method This study is a single-arm, open, prospective clinical study planned to enroll 35 untreated patients with stage CNLCⅢ hepatocellular carcinoma. Eligible pts received VIC （oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-fluorouracil bolus 400 mg/m² on day 1, and 5-fluorouracil infusion 2400 mg/m² for 46 hours; q3w; 6 cycles）, combined with apatinib （250 mg qd） and camrelizumab （200 mg q3w）. The primary study endpoints were objective response rate （ORR） assessed based on the RECIST 1.1 criteria, while the secondary study endpoints included： ORR assessed based on RECIST 1.1, mRECIST criteria, and disease control rate （DCR）, progression-free survival time （PFS）, overall survival time （OS）, surgical conversion rate, adverse reactions （AE）, etc. Results Data of 26 liver cancer patients who met the entry criteria and signed the consent form from April 2021 to April 2023 were collected and analyzed. The median follow-up was 13 months, ORR 61.5% （RECISTv1.1） and 73.1% （mRECIST）, cCR rate 26.9%, pCR 23.1%, DCR 96.2%, and mPFS and mOS were not reached, both over 9 months. The surgical conversion rate was 57.7%, all achieving R0 resection. The incidence of treatment-related adverse effects （TRAE） grade 3 AEs was 50%. Conclusion The triplet treatment of VIC plus camrelizumab and apatinib showed promising antitumor activity and acceptable safety for CNLC stage Ⅲ HCC,and the preliminary study effect is similar to that of FOLFOX-HAIC combined with camrelizumab and apatinib . Especially for patients with main portal vein cancer thrombus, the combined treatment scheme is worthy of clinical application.

Construction and validation of a prognostic risk model for hepatocellular carcinoma based on angiogenesis-related lncRNAs

LUO Wan-rong, ZHANG Wen-yue, LUO Bao-ming

2024, 24(01):  7-13.  DOI: 10.3969/j.issn.1009-976X.2024.01.002

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Objective To construct and validate a prognostic risk model based on long non-coding RNA associated with angiogenesis in hepatocellular carcinoma. Methods LncRNAs associated with angiogenesis were screened by Pearson correlation analysis and differentially expressed lncRNAs were extracted. Multivariate Cox regression combined with LASSO regression was used to establish the risk prognosis model, which was verified by survival analysis, independent prognosis analysis and risk analysis. The relationship between risk score and the expression of immune cells, immune microenvironment and immune checkpoint was analyzed. Results In the risk prognosis model constructed by screened angiogenation-related lncrnas, HCC patients with higher risk scores had worse prognosis, and the infiltration of macrophages and Treg cells also proved that risk scores were correlated with changes in the immune microenvironment. Conclusion The model has good reliability and validity in predicting the prognosis of patients with hepatocellular carcinoma.

Correlation analysis of FAM72 gene family in prognosis and immune infiltration of hepatocellular carcinoma

LIN Kun-peng, BA Ming-chen, TANG Yun-qiang, WANG Jia-kang, LIN Xiao-chun

2024, 24(01):  14-25.  DOI: 10.3969/j.issn.1009-976X.2024.01.003

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Objective To analyze the expression, prognostic and immune infiltrationroles of FAM72 gene family （FAM72s） in hepatocellular carcinoma （HCC）. Methods TCGA was used to analyze the expression of FAM72s in patients with HCC, the differences among different clinical characteristics, and independentprognostic values. The relationships of FAM72s expression and overall survival （OS） were assessed using TCGA and Kaplan-Meier plotter. STRING was used to detect the protein-proteininteraction （PPI） networks forFAM72s. The relationship of FAM72s expression and immune infiltration was performed by the ssGSEA. We used GEPIA to evaluate the correlation of FAM72s expression with biomarkers of immune cells and immune checkpoints in HCC. Results The expressions of FAM72A-D in HCC were significantly increased compared with those in normal liver tissues （P<0.05）. The OS in the high FAM72A-D expression group were shorter than those in the low expression group （P<0.05）. Univariate/multivariate regression analysisand ROC curve indicated that FAM72A-D could be used as an independent risk factor affecting the prognosis of HCC patients （P<0.05）. PPI networks showed that FAM72A-D compared with various proteinsparticipated in the progression of HCC. The results of immune infiltration analysis showed that the expression level of FAM72A-D was significantly correlated with the levels of mostinfiltrating immune cells and various biomarkers of immune cells. PD-1, PD-L1, and CTLA-4 levels were positively correlated with FAM72A-D expression. Conclusions FAM72s were highly expressed in HCC tissues and were associated with immune infiltration and poor prognosis. FAM72s may be significant biomarkers of HCC.

Construction of a bladder cancer prognostic risk model based on DNA damage repair and its application in predicting the effectiveness of immunotherapy

LUO Hong-cheng, ZHANG Jia-hao, HE Zhao-hui

2024, 24(01):  26-36.  DOI: 10.3969/j.issn.1009-976X.2024.01.004

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Objective This study aims to explore the construction of a risk model based on DNA Damage Repair Genes （DDRGs） that can accurately predict the survival prognosis and immunotherapy outcomes of bladder cancer patients. Methods Initially, RNA sequences and clinical information downloaded from the TCGA-BLCA dataset were analyzed through univariate Cox, Least Absolute Shrinkage and Selection Operator （LASSO）, and multivariate Cox analyses to identify DNA Damage Repair Genes （DDRGs） and construct a prognostic risk model. Subsequently, the Kaplan-Meier survival curve was utilized to assess survival differences, the Receiver Operating Characteristic （ROC） curve to validate model performance, and nomograms were constructed incorporating clinical features for further validation.Lastly, clinical features were subjected to stratified analysis, and the treatment effects of immune status and Immune Checkpoint Inhibitors （ICIs） were further evaluated through Gene Set Enrichment Analysis （GSEA）. Results The risk model constructed with 11 DNA damage repair-related genes showed that bladder cancer patients with high-risk scores had significantly lower survival rates than those with low-risk scores. Conclusion The prognostic risk model constructed based on DNA damage repair in this study can effectively predict the survival prognosis of bladder cancer patients and their responsiveness to treatment with Immune Checkpoint Inhibitors （ICIs）.

Study on the diagnostic value of preoperative urinary BTA and NMP22 quantitative detection in bladder cancer

YANG Li-bin, XU Han-biao, YANG Hai-chao, ZHONG Ji-sheng, LIAO Zhen-wen

2024, 24(01):  37-41.  DOI: 10.3969/j.issn.1009-976X.2024.01.005

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Objective To explore the diagnostic value of combined determination of bladder tumor of antigen（BTA）and nuclear matrix protein 22（NMP22）in urine before operation for bladder cancer. Methods Seventy-three patients with bladder cancer diagnosed in the Department of Urology of Huizhou Central People′s Hospital from January 2021 to September 2022 were selected as the observation group, and 73 patients with benign urinary diseases in the same period were selected as the control group. The quantitative levels of BTA and NMP22 in urine of the two groups were detected before operation. According to the detection results, the single and combined diagnostic value of the two indexes in bladder cancer were retrospectively analyzed, and the positive rates of the two indexes in patients with different clinical tumor conditions were analyzed. Results The preoperative urinary BTA quantitative levels in the observation group and the control group were （997.85±237.73） pg/ml and （691.33±190.16） pg/ml ;NMP22 expression levels were（8.57±1.49）ng/ml and （6.23±1.29） ng/ml, respectively. Compared with the control group, the levels of urinary BTA and NMP22 in the observation group were significantly higher than those in the control group （P<0.01）. The sensitivities of preoperative urine BTA and NMP22 in the diagnosis of bladder cancer were 76.7% and 78.1% respectively, the specificity were 90.4% and 91.8%, and the areas under the curve（AUC） were 0.849 and 0.867 respectively. At this time, the best cut-off values of 834.55 pg/ml and 7.47 ng/ml were respectively. The sensitivity, specificities and AUC of the combined diagnosis were 89.0%, 87.7% and 0.931 respectively, and the sensitivity and AUC were higher than those of single detection. There were no significant differences in the positive rates of BTA and NMP22 among patients with different age, sex, BMI and smoking（P>0.05）, but there was significant difference in the positive rates of BTA and NMP22 among patients with different tumor diameter, tumor number, tumor grade and tumor stage（P<0.05）. Conclusion The quantitative determination of urinary BTA and NMP22 before operation has a good diagnostic efficacy for bladder cancer, and it has the advantages of non-invasive, convenient and batch detection, and the combined detection of the two can improve the sensitivity of diagnosis and reduce the possibility of missed diagnosis, so it is worthy to be used in clinical practice.

Effects of knockdown BRIX1 on proliferation, migration and invasion of triple negative breast cancer cells

DONG Yi-ming, SHI Chuan-ping, LIAO Jian-you

2024, 24(01):  42-48.  DOI: 10.3969/j.issn.1009-976X.2024.01.006

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Objective To investigate the function of BRIX1, a large subunit component of ribosome, in triple negative breast cancer cell line in vitro. Methods The expression difference of BRIX1 in normal tissue and triple negative breast cancer was analyzed by GEPIA2 database. Two SiRNAs were designed and transferred into triple negative breast cancer cell lines HS578T and MDA-MB-231 respectively to silence the expression of BRIX1, and Western Blot was used to verify the knock inefficiency of BRIX1. The proliferation of cells after BRIX1 knockdown was detected by CCK-8 and colony cloning formation assay, and the invasion and migration ability of cells after BRIX1 knockdown was detected by Transwell assay. MDA-MB-231 cells were divided into three groups, which were transferred into siNC, siBRIX1#1 and siBRIX1#2 respectively, and total RNA of the cells was extracted for RNA-Seq detection, and the difference of gene expression was analyzed. Results The results of GEPIA2 database showed that BRIX1 was highly expressed in triple negative breast cancer （P<0.05）, and the number of clones was decreased in HS578T and MDA-MB-231 cells （P<0.05）. The OD value of cck8 was decreased, which proved that the cell proliferation activity decreased after knocking down BRIX1. TranswellTM experiment showed that the invasion and migration ability of breast cancer was weakened after knocking down BRIX1. Biological process （BP）, molecular function （MF）, and cell composition （CC） of RNA-seq data were enriched by GO, and the top10 signaling pathways with high correlation were finally revealed. The results showed that after knockdown BRIX1, ERBB-ERK and WNT signaling pathways were activated, while P53 signaling pathways were inhibited. Conclusion Down-regulated BRIX1 expression could significantly inhibited the proliferation, migration and invasion of triple negative breast cancer cells, it suggesting that BRIX1 gene could be a potential molecular target for triple negative breast cancer therapy.

The effect of metabolic syndrome on prognosis of non-triple negative breast cancer

WU Wen-xia, ZHANG Meng

2024, 24(01):  49-53.  DOI: 10.3969/j.issn.1009-976X.2024.01.007

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Objective To explore the prognostic value of metabolic syndrome （MS） and its components in outcome of patients with non-Triple Negative Breast Cancer（non-TNBC）. Methods The study included the newly diagnosed non-TNBC during Jan 1 2016 and Mar 30 2017. Clinical and pathological data were collected, and the patients were followed up for 3 years. The Kaplan-Meier analysis was used to explore the association between the MS and its components and the overall survival （OS）. The prognosis factors were analyzed by the multivariable Cox proportional hazards regression models. Results 194 patients were included with 12 in MS group and 168 in non-MS group. During the follow-up, there were 2 patients died in MS group, which OS rate was 81.8%. While in the non-MS group, 2 patients died and the OS rate was 98.8% （P<0.05）. After adjusting the menopausal status age, tumor stage and pathological factors, MS was the independently risk factor for poor OS （HR=62.788, 95%CI：1.342-2937.323, P<0.05）. The patients with two or more items of hypertension, hyperglycemia and dyslipidemia had higher death risk, compared with the patient with only one or none of them （HR=23.397, 95%CI：1.918-285.405, P<0.05）. Conclusion MS was associated with poor prognosis of non-Triple Negative Breast Cancer.

Prognostic value of HIST1H4F gene methylation in triple-negative breast cancer

YAN Shan-shan, LEI Wen, LI Shuai-jie, WANG Yong-nan

2024, 24(01):  54-58.  DOI: 10.3969/j.issn.1009-976X.2024.01.008

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Objective To investigate prognostic value of HIST1H4F gene methylation in triple-negative breast cancer. Methods Thirty-one fresh breast cancer tissue samples and normal breast tissue samples were collected. After DNA extraction, bisulfite was used for methylation transformation. Fluorescence quantitative PCR was used to detect the methylation of HIST1H4F gene, and the difference of HIST1H4F gene methylation in cancer tissue samples and normal breast tissue was analyzed. The relationship between methylation of HIST1H4F gene and prognosis of triple-negative breast cancer was analyzed.At the same time, paraffin specimens of 37 cases of triple-negative breast cancer were collected, DNA was extracted and processed by the same method, and HIST1H4F gene methylation was detected to analyze the relationship between HIST1H4F gene methylation and prognosis of triple-negative breast cancer. Results The HIST1H4F methylation positive rates were 74.2% （23/31） in both normal and cancer tissues, and there was no significant difference between the two groups （χ²=0.000, P=1.000）. the HIST1H4F methylation positive rate in triple-negative breast cancer was higher than that in non-triple-negative breast cancer （93.8% vs. 53.3%, P=0.015）, HIST1H4F methylation-positive group had higher HIST1H4F grade Ⅲ and ER negative ratio than HIST1H4F methylation-negative group （60.9% vs. 12.5%, P=0.037; 69.6% vs. 25.0%, P=0.043）. For HIST1H4F methylation in paraffin tissue specimens of triple-negative breast cancer and found a HIST1H4F methylation positive rate of 27.0%,there was no significant difference between HIST1H4F methylation positive and negative groups in DFS （50.0% vs. 66.7%, χ²=1.141, P=0.285） and OS （90.0% vs. 96.3%, χ²=1.635, P=0.201）. Conclusion The positive rate of HIST1H4F gene methylation in triple negative breast cancer is high in fresh tissue samples, and histological grade Ⅲ and ER negative ratios were high in HIST1H4F gene methylation-positive breast cancer. While HIST1H4F methylation positive rate was low in paraffin tissue samples of triple-negative breast cancer. Whether HIST1H4F methylation is associated with triple-negative breast cancer prognosis remains to be determined and further studies are needed.

Efficacy of reconstructing anterior spinal column function in thoracolumbar tuberculosis by lesion removal via unilateral pedicle approach

FANG Lei, CHEN Xin-ying, YI Yan-bin, CHEN Zi-hua

2024, 24(01):  59-64.  DOI: 10.3969/j.issn.1009-976X.2024.01.009

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Objective To study the efficacy of anterior spinal column function in the reconstruction of thoracolumbar tuberculosis. Methods Fifty-three patients with thoracolumbar tuberculosis admitted to Heyuan People′s Hospital from January 2018 to April 2022 were selected as the observation group, and treated by posterior debridement via unilateral pedicle approach with bone grafting and internal fixation. Fifty-two patients with thoracolumbar tuberculosis admitted to our hospital from January 2014 to December 2017 were selected as the control group and treated with traditional posterior debridement with bone graft and internal fixation. The intraoperative and postoperative indicators, erythrocyte sedimentation rate （ESR）, C-reactive protein （CRP）, Cobb angle, Cobb angle loss rate, digital pain （NRS） score, Oswestry dysfunction index, American Spine Injury Association Neurological Function （ASIA） grade and complications were compared between the two groups. Results The postoperative drainage volume of observation group was lower than that of control group （P<0.05）. At the last follow-up after surgery, ESR and CRP were decreased in both groups （P<0.05）. At the last postoperative follow-up, the Cobb Angle and Oswestry disability index in the sagittal plane of the lesion were decreased in both groups compared with those before surgery （P<0.05）, the cobb Angle loss rate in the observation group was lower than that in the control group （P<0.05）, the NRS score in the observation group was lower than that in the control group at the last postoperative follow-up （P<0.05）. The proportion of grade C-D in observation group was lower than that in control group （P<0.05）, and the proportion of grade E in observation group was higher than that in control group （P<0.05）. There were no significant differences in the total incidence of pleural effusion, incision infection, intercostal neuralgia and cerebrospinal fluid leakage between the two groups （P>0.05）. Conclusion Patients with thoracolumbar spinal tuberculosis have less postoperative drainage rate, lower postoperative cobb angle loss rate and lower pain degree, and better neurological function recovery.

Clinical study on characterization of the arterial blood supply in patients with various grades of hemorrhoids

WU Hai-xiong, LI Qiang, YAO Qi, LIN Li-fen

2024, 24(01):  65-68.  DOI: 10.3969/j.issn.1009-976X.2024.01.010

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Objective To study the characterization of arterial blood supply in patients of the internal hemorrhoidals. Methods The caliber and flow of arterial blood supply in 80 patients with hemorrhoids of Goligher grades Ⅰ~Ⅳ and 20 healthy volunteers were examined by means of transperineal color Doppler ultrasound. Results Eighty patients with hemorrhoids of Goligher grades Ⅰ-Ⅳ were compared with 20 healthy volunteers by means of transperineal color Doppler ultrasound. The mean caliber of the arterial branches in the study group with hemorrhoids was 1.90±0.85 mm and 0.97±0.24 mm in the control group （P<0.001）. The arterial blood flow was significantly higher in patients with hemorrhoids47.3±28.3 cm/s than in the control group 15.6±5.0 cm/s, P<0.01. Conclusion Our findings demonstrate that increased caliber and arterial blood flow are correlated with the severity of hemorrhoids. Transperineal color Doppler ultrasound hopefully providy an appropriate method to choose the treatment in patients with hemorrhoids.

Case Report

Successful liver transplant after Yttrium-90 microsphere radioembolization combined with targeted and immunotherapy： a case report and literature review

CHEN Huan-quan, HE Cai-hua, DAI Tian-xing, HUANG Wen-sou, YUAN Feng, WANG Xiao-ming, LUO Yan-jun, WANG Guo-ying

2024, 24(01):  69-75.  DOI: 10.3969/j.issn.1009-976X.2024.01.011

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Objective To discuss successful liver transplantation in advanced hepatocellular carcinoma patients after yttrium-90 microsphere radioembolization （Y90-RE） combination of targeted and immunotherapy： a clinical case report and literature review. Methods A retrospective analysis of a case of advanced hepatocellular carcinoma patient who underwent successful liver transplantation after Y90-RE combination of targeted and immunotherapy at our center was performed. The relevant treatment methods and postoperative disease changes were analyzed, and the latest domestic and international literature progress was summarized. Results The patient was a 41-year-old middle-aged man. After Y90-RE combination target-immune therapy, he underwent liver transplantation. During the perioperative period, human immunoglobulin pulse therapy was administered, and a combined immunosuppressive scheme of tacrolimus and glucocorticoids was given early after surgery. The patient′s liver function gradually improved within 2 weeks after surgery. However, mild elevations of transaminases were detected on the 15th and 68th days after surgery, accompanied by mild acute rejection identified by liver biopsy. Both episodes were resolved by strengthening immunosuppressive treatment. Now, after 6 months of follow-up, the patient′s liver function is normal, and no tumor recurrence is observed. Conclusion Y90-RE combined target-immune therapy can provide a treatment option for advanced hepatocellular carcinoma patients.

Review

Predictive value of tumor infiltrating lymphocytes in breast cancer patients under different molecular subtypes

MENG Lan-lan, JIN Hao, YAO Yan-dan

2024, 24(01):  76-86.  DOI: 10.3969/j.issn.1009-976X.2024.01.012

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Tumor-infiltrating lymphocytes （TILs） are an important part of the tumor microenvironment and play an important role in the anti-tumor immune response of breast cancer. According to gene expression analysis or immunohistochemical markers of estrogen receptor （ER）, progesterone receptor （PR）, human epidermal growth factor receptor 2 （HER2） expression, breast cancer can be divided into triple negative breast cancer （TNBC）, HER2 positive breast cancer, Luminal breast cancer. The predictive value of TILs is different in different subtypes of breast cancer. The prognosis of TILs in breast cancer varies not only because of the different levels of TILs, but also because of the presence of both anti-tumor and pro-tumor subgroups in TILs, and the various subgroups of TILs differs in different patients.