1.Impact of Toxoplasma gondii type I rhoptry protein 16 on programmed cell death ligand 1 expression and its binding to programmed cell death 1 in lung adenocarcinoma cells
Guangqi LI ; Yuning ZHOU ; Shaohan MA ; Mei TIAN ; Tiantian DANG ; Zhijun ZHAO
Chinese Journal of Schistosomiasis Control 2025;37(1):44-54
Objective To investigate the impact of Toxoplasma gondii type I, II and III rhoptry protein 16 (ROP16) on programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinoma cells, and to examine the effects of T. gondii type I ROP16 protein on the relative PD-L1 expression, the relative PD-L1 distribution on the cell membrane surface, and the binding of programmed cell death 1 (PD-1) to PD-L1 in lung adenocarcinoma cells. Methods Lentiviral vectors overexpressing T. gondii type I, II and III ROP16 proteins were generated, and transfected into the human lung adenocarcinoma A549 cell line. A549 cells were used as a blank control group, and A549 cells transfected with an empty lentiviral expression vector were used as a negative control group, while A549 cells transfected with lentiviral vectors overexpressing T. gondii type I, II and III ROP16 proteins served as experimental groups. Stably transfected cells were selected with puromycin and verified using Western blotting, quantitative real-time PCR (RT-qPCR), and immunofluorescence assays. The PD-L1 expression was quantified at translational and transcriptional levels using Western blotting and RT-qPCR assays in A549 cells in the five groups, and the relative PD-L1 distribution was detected on the A549 cell membrane surface using flow cytometry. In addition, the effect of T. gondii type I ROP16 protein on the PD-1/PD-L1 binding was measured in A549 cells using enzyme-linked immunosorbent assay (ELISA). Results The relative ROP16 protein expression was 0, 0, 1.546 ± 0.091, 1.822 ± 0.047 and 2.334 ± 0.089 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 1 339.00,P < 0.001), and the relative ROP16 mRNA expression was 2.153 ± 0.949, 2.436 ± 1.614, 14.343 ± 0.020, 12.577 ± 0.285 and 15.090 ± 0.420 in the blank control group, negative control group and the T. gondii type I, II and III ROP16 protein overexpression groups, respectively (F = 483.50,P < 0.001). The ROP16 expression was higher in the T. gondii type I, II and III ROP16 protein overexpression groups than in the blank control group at both translational and transcriptional levels (allP values < 0.001). Immunofluorescence assay revealed that T. gondii type I, II and III ROP16 proteins were predominantly localized in A549 cell nuclei. Western blotting showed that the relative PD-L1 protein expression was 0.685 ± 0.109, 0.589 ± 0.114, 1.007 ± 0.117, 0.572 ± 0.151, and 0.426 ± 0.116 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 9.46,P < 0.05), and RT-qPCR assay quantified that the relative PD-L1 mRNA expression was 1.012 ± 0.190, 1.281 ± 0.465, 1.950 ± 0.175, 0.889 ± 0.251, and 0.230 ± 0.192 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 14.18,P < 0.05). The PD-L1 expression was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group at both translational and transcriptional levels (both P values < 0.05). Flow cytometry detected that the relative distributions of PD-L1 protein were (10.83 ± 0.60)%, (11.23 ± 0.20)%, and (14.61 ± 0.50)% on the A549 cell membrane surface (F = 28.31, P < 0.05), and the relative distribution of PD-L1 protein was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group and negative control group (both P values < 0.001). ELISA measured significant differences in the absorbance (A) value among the T. gondii type IROP16 protein overexpression group, the blank control group and the negative control group if the concentrations of the recombinant PD-1 protein were 0.04 (F = 10.45, P < 0.05), 0.08 μg/mL (F = 11.68, P < 0.05) and 0.12 μg/mL (F = 52.68, P < 0.05), and the A value was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group and the negative control group (both P values < 0.05), indicating that T. gondii type IROP16 protein promoted the PD-L1/PD-1 binding in A549 cells in a concentration-dose manner. Conclusions T. gondii type IROP16 protein overexpression may up-regulate PD-L1 expression in A549 cells at both transcriptional and translational levels and the relative PD-L1 distribution on the A549 cell membrane surface, and affect the PD-1/PD-L1 binding in a concentration-dependent manner.
2.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
3.Study on mechanical stability of maxillary LeFort Ⅰ type osteotomy after fixation with mortise and tenon and absorbable plate
Yankun ZHANG ; Zixuan SHEN ; Ran ZHANG ; Lijia DONG ; Yu TIAN ; Li LU ; Mingliang YANG ; Guangqi YAN
Chinese Journal of Stomatology 2025;60(6):635-643
Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.
4.Microwave ablation for pediatric reninoma: a case report
Zhechen YU ; Guangqi ZENG ; Xiaoyu YUAN ; Tianyi WANG ; Yu ZHANG ; Ting FENG ; Guohui LI ; Ting ZHANG ; Mingcui FU ; Xiangming YAN ; Shu DAI
Chinese Journal of Urology 2025;46(5):395-396
Reninoma is a rare renal secretory tumor,prevalent in the young population. This disease is mostly surgically resected,and the use of microwave ablation to treat reninoma in children is scarce. A case of reninoma in a child was reported in this paper. The patient presented with refractory hypertension,hypokalemia,hyperreninemia and hyperaldosteronemia. Enhanced CT and contrast-enhanced ultrasound showed mass in the lower pole of the right kidney,which was considered as reninoma and microwave ablation was performed. The renin concentration decreased to 68.42 pg/ml at 4 hours after surgery. After 1 year of postoperative follow-up,there was no recurrence of hypertension and hypokalemia,and no signs of tumor recurrence were seen on repeated ultrasound examinations.
5.Imaging features and related factors of retinal splits and paravascular abnormalities in myopic macular region
Chenyu LU ; Guangqi AN ; Pei LIU ; Shu LI ; Min ZHANG ; Xuemin JIN ; Liping DU
Chinese Journal of Ocular Fundus Diseases 2025;41(2):106-112
Objective:To observe the imaging features of extramacular retinoschisis (EMRS) and paravascular abnormalities (PVA) in myopic patients, and preliminary analyze the differences in age, best corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), and subfoveal choroidal thickness (SFCT).Methods:A cross-sectional clinical study. A total of 60 myopia patients with EMRS who were admitted to Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from January 2023 to June 2024 were included in the study. There were 18 male cases with 18 eyes and 42 female cases with 42 eyes. Age was (37.57±17.14) years; SE was (-10.76±4.66) D; AL was (28.36±1.87) mm. According to the characteristics of ultra-wide-angle optical coherence tomography images, PVA was divided into perivascular cysts (PC), perivascular microfolds (PM) and perivascular lamellar holes (PLH). According to the splitting level, EMRS can be divided into inner layer, middle layer and outer layer. According to SE, the affected eyes were divided into low myopia group, moderate myopia group and high myopia group. The occurrence of EMRS near optic disc, supratemporal, suprasal and subnasal, as well as the clinical characteristics of patients with EMRS at different locations, levels and forms of PVA were observed. Age, BCVA, SE, AL and SFCT of EMRS patients at different locations and levels were compared by independent sample t test. χ2 test or Fisher exact probability test were used to compare the categorical variables between groups. Results:In 60 eyes, EMRS were located in supratemporal, infratemporal, supranasal, subnasal, and paratopic discs in 36, 43, 15, 13, and 14 eyes, respectively. The EMRS in the inner and outer layers were 59 (98.3%, 59/60) and 35 (58.3%, 35/60) eyes, respectively. PVA was present in 47 eyes (78.3%, 47/60). Among them, PC, PM and PLH were 45, 39 and 18 eyes, respectively. The age of those with paratopic splitting was older than those without paratopic splitting ( t=2.720). Those with temporal splitting had worse BCVA and longer AL than those without splitting ( t=2.139, 2.119). Those with subnasal splitting had worse BCVA, higher myopia, longer AL and thinner SFCT than those without splitting. The differences were statistically significant ( t=2.926, -2.640, 2.635, -3.938; P<0.05). Compared with other types of EMRS, patients with inner EMRS had younger age ( t=-2.383), better BCVA ( t=-4.825), shorter AL ( t=-4.767), lower myopia ( t=4.791), and thicker SFCT ( t=4.791); patients with full-layer EMRS were older ( t=2.419), worse BCVA ( t=3.656), longer AL ( t=2.677), higher degree of myopia ( t=-2.755), and thinner SFCT ( t=-3.283), with statistical significance ( P<0.05). There was significant difference in SFCT among patients with or without PC ( t=-2.396, P<0.05). Compared with eyes without PM and PLH, eyes with PM had worse BCVA, longer AL, higher myopia, and thinner SFCT, and the differences were statistically significant (PM: t=2.514, 3.078, -2.811, -4.205; P<0.05; PLH: t=2.514, 2.992, -2.949, -1.773; P<0.05). Conclusions:EMRS primarily occurs in the temporal side, with the highest frequency in the inner layer. Patients with inner-layer EMRS are younger, have better BCVA, shorter AL, lower myopia, and thicker SFCT, whereas patients with full-layer EMRS exhibit the opposite characteristics.
6.Fundus imaging features of glucocorticoid-related central serous chorioretinopathy
Bo JIN ; Pei LIU ; Shu LI ; Chenyu LU ; Guangqi AN ; Haiyan ZHU ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(5):358-363
Objective:To compare and observe the fundus imaging characteristics of eyes with glucocorticoid-related central serous chorioretinopathy (CSC).Methods:A retrospective clinical study. A total of 149 CSC patients with 166 eyes diagnosed at Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from March 2021 to October 2024 were included in the study. The duration of the disease from the appearance of symptoms to treatment was less than 3 months. All affected eyes underwent best-corrected visual acuity (BCVA), fundus color photography, swept-source optical coherence tomography (SS-OCT), and fundus fluorescein angiography (FFA) examinations. BCVA was tested using an international standard vision chart and converted into logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The SS-OCT instrument measured subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascular volume (CVV), and the width and height of flat irregular pigment epithelial detachment (FIPED). FIPED, subretinal fibrin, and choroidal layer strong reflective spots were identified from SS-OCTA B-scan images; multiple leakages (leak points >3) were identified from FFA images. Based on the presence or absence of a clear history of glucocorticoid administration before the onset, patients were divided into glucocorticoid-related and non-glucocorticoid-related groups, comprising 41 patients with 53 eyes and 108 patients with 113 eyes, respectively. Clinical and fundus imaging characteristics of the two groups were compared. The comparison of quantitative data between the two groups was performed using independent samples t test or non-parametric independent samples Wilcoxon test; the comparison of qualitative data was performed using χ2 test. Results:Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had a smaller male-to-female ratio and a higher bilateral incidence, and the differences were statistically significant ( χ2=4.925, 17.849; P<0.05). The logMAR BCVA for the glucocorticoid-related and non-glucocorticoid-related groups were 0.45±0.33 and 0.21±0.21, respectively; SFCT were (644.43±131.91) and (507.26±121.79) μm; CMT were (389.51±233.45) and (362.59±140.85) μm; CVV were (4.44±1.07) and (3.67±0.82) mm 3; FIPED incidence were 58.49% (31/58) and 20.35% (23/113), respectively; FIPED width and height were (1 122.01±533.98) and (742.90±388.79) μm, and (99.13±92.17) and (33.01±15.99) μm; subretinal fibrin were observed in 24 (45.28%, 24/53) and 15 (13.27%, 15/113) eyes; choroidal strong reflections were found in 38 (71.70%, 38/53) and 45 (39.82%, 45/113) eyes; multiple leak points were identified in 35 (66.03%, 35/53) and 40 (35.40%, 40/113) eyes, respectively. Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had worse BCVA ( Z=-4.984), thicker SFCT ( t=6.586), larger CVV ( t=5.160), higher incidence of FIPED ( χ2=23.908), and greater width and height of FIPED ( t=2.895, Z=-3.703). The glucocorticoid-related group also had a significantly increased incidence of subretinal fibrin, choroidal strong reflections, and multiple leak points, with all differences being statistically significant ( χ2=20.565, 14.663, 13.675; P<0.05); however, the comparison of CMT showed no statistically significant difference ( Z=-0.651, P>0.05). Conclusion:Compared with non-glucocorticoid-related CSC, glucocorticoid-related CSC patients have poorer vision, are more likely to affect both eyes, show no gender bias; choroidal vascular dilation is more significant, and damage to the outer retina and retinal pigment epithelium is more severe.
7.Comparison and correlation analysis of clinical and imaging features of focal choroidal excavation
Pei LIU ; Shu LI ; Chenyu LU ; Guangqi AN ; Bo JIN ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(8):613-620
Objective:To compare the clinical and imaging characteristics of eyes with idiopathic focal choroidal excavation (FCE) and acquired FCE, and to preliminarily analyze the association of FCE with different fundus diseases.Methods:A retrospective clinical study. A total of 90 patients (93 eyes) diagnosed with FCE at the Ophthalmology Department of The First Affiliated Hospital of Zhengzhou University from March 2021 to May 2024 were included in the study. All affected eyes underwent best-corrected visual acuity (BCVA) testing, intraocular pressure (IOP) measurement, ophthalmoscope, fundus color photography, and swept-source optical coherence tomography (SS-OCT). SS-OCT was used to measure subfoveal choroidal thickness (SFCT), choroidal thickness at the temporal, nasal, and inferior margins of the FCE, as well as the maximum width and depth of the FCE. Based on the presence of concomitant fundus diseases, FCE cases were divided into an idiopathic FCE group (51 eyes) and an acquired FCE group (42 eyes). Clinical characteristics at the initial and final visits were compared between the two groups. Clinical features were also analyzed for acquired FCE eyes with different associated fundus diseases. A logistic regression model was used to identify potential risk factors for FCE coexisting with other fundus diseases.Results:Compared to the idiopathic FCE group, the acquired FCE group had significantly decreased BCVA ( Z=?8.290), significantly increased FCE width ( Z=?2.762), and significantly higher incidence rates of saucer-shaped FCE ( χ2=8.352) and ellipsoid zone disruption ( χ2=7.999). These differences were all statistically significant ( P<0.05). No significant differences were found between the two groups in age, gender distribution, IOP, foveal involvement, proportion of conforming FCE, retinal pigment epithelium-Bruch’s membrane rupture, presence of hyperreflective material under the excavation, presence of surrounding thick vessels, FCE depth, SFCT, or choroidal thickness at the inferior, temporal, and nasal margins of the FCE ( P>0.05). Logistic regression analysis revealed that FCE width (odds ratio=1.002, 95% confidence interval: 1.001-1.004, P=0.005) was the sole risk factor for FCE coexisting with other fundus complications. In both the idiopathic and acquired FCE groups, FCE depth and width remained relatively stable during follow-up. BCVA improved in the acquired FCE group after treatment. Conclusions:FCE can coexist with various fundus diseases. FCE width is the only risk factor for the development of other fundus complications in FCE-affected eyes. Treating retinal or choroidal diseases associated with acquired FCE can provide visual benefits to patients.
8.Development of a clinical prediction model for cervical instability in young and middle-aged adults based on machine learning
Jing LI ; Guangqi LU ; Minghui ZHUANG ; Ying CUI ; Zhangjingze YU ; Xinyue SUN ; Mingming MA ; Liguo ZHU ; Jie YU
Chinese Journal of Tissue Engineering Research 2025;29(33):7203-7210
BACKGROUND:Cervical instability is a common orthopedic disease in young and middle-aged people,and is the early manifestation of cervical spondylosis,which has a great impact on the quality of life of patients.Therefore,early diagnosis of cervical instability to implement early intervention has positive clinical and social significance.OBJECTIVE:The clinical prediction model of cervical instability in young and middle-aged people was constructed based on machine learning to realize early screening of cervical instability in young and middle-aged people before X-ray examination.METHODS:From September 2022 to October 2023,155 young and middle-aged adults with cervical instability and 88 with non-cervical instability recruited through recruitment advertisements and spinal department outpatient of Wangjing Hospital,China Academy of Chinese Medical Sciences were selected as research subjects.The research subjects'general information,living and working habits,discomfort symptoms,visual analog scale score,Neck Disability Index,and 36-ltem Short Form Health Survey were collected on site based on questionnaires.The above information was used as predictive factors.After screening,six machine learning algorithms of Support Vector Machine,LightGBM,RandomForest,Logistic,AdaBoost,and XGBClassifier were used to train the model by ten-fold cross-validation method,and the clinical prediction model of cervical instability was constructed.Area under the curve was used as the main evaluation index.Univariate analysis was performed on the predictors,and SHAP method was used to rank the importance of the predictors.Correlation heat maps were used to show the degree of linear correlation between the predictors and the cervical instability.RESULTS AND CONCLUSION:(1)Among the six machine learning models,RandomForest model was chosen as the final prediction model,including nine predictors,such as age,body mass index,neck circumference/neck length,visual analog scale score,Neck Disability Index,bodily pain,general health,vitality,and mental health,area under the curve=0.725 4,and the calibration degree was good.It could be used as a reference tool for early screening of cervical instability in young and middle-aged people.(2)There were significant differences in age,visual analog scale score,Neck Disability Index,bodily pain,general health,and vitality between the two groups(P<0.05).(3)The order of importance of predictors was age,Neck Disability Index,visual analog scale score,general health,body mass index,vitality,bodily pain,neck circumference/neck length,mental health,among which age,visual analog scale score,Neck Disability Index were positively correlated with cervical instability,while general health,body mass index,vitality,bodily pain,neck circumference/neck length,and mental health were negatively correlated with cervical instability.
9.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
10.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

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