1.Hub biomarkers and their clinical relevance in glycometabolic disorders: A comprehensive bioinformatics and machine learning approach.
Liping XIANG ; Bing ZHOU ; Yunchen LUO ; Hanqi BI ; Yan LU ; Jian ZHOU
Chinese Medical Journal 2025;138(16):2016-2027
BACKGROUND:
Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment.
METHODS:
Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models.
RESULTS:
Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells.
CONCLUSIONS
Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6 may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning
;
Humans
;
Computational Biology/methods*
;
Biomarkers/metabolism*
;
Diabetes Mellitus, Type 2/genetics*
;
Animals
;
Mice
;
Gluconeogenesis/physiology*
;
Gene Expression Profiling
;
Transcriptome/genetics*
;
Gene Regulatory Networks/genetics*
;
Clinical Relevance
2.Research progress on prevention and treatment of hepatocellular carcinoma with traditional Chinese medicine based on gut microbiota.
Rui REN ; Xing YANG ; Ping-Ping REN ; Qian BI ; Bing-Zhao DU ; Qing-Yan ZHANG ; Xue-Han WANG ; Zhong-Qi JIANG ; Jin-Xiao LIANG ; Ming-Yi SHAO
China Journal of Chinese Materia Medica 2025;50(15):4190-4200
Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans
;
Gastrointestinal Microbiome/drug effects*
;
Carcinoma, Hepatocellular/microbiology*
;
Liver Neoplasms/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Medicine, Chinese Traditional
3.Clinical efficacy of open reduction and internal fixation with plates versus minimally invasive Kirschner wire fixation for osteoporotic Colles' fractures.
Jun-Wei ZHANG ; Jin-Yong HOU ; Zhao-Hui LI ; Zhen-Yuan MA ; Xiang GAO ; Hong-Zheng BI ; Ling-Ling CHEN ; Hai-Tao WANG ; Wei-Zhi NIE ; Yong-Zhong CHENG ; Xiao-Bing XI
China Journal of Orthopaedics and Traumatology 2025;38(1):18-24
OBJECTIVE:
To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients.
METHODS:
Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores.
RESULTS:
The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05).
CONCLUSION
Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans
;
Female
;
Male
;
Middle Aged
;
Aged
;
Fracture Fixation, Internal/instrumentation*
;
Bone Wires
;
Bone Plates
;
Retrospective Studies
;
Colles' Fracture/surgery*
;
Minimally Invasive Surgical Procedures/methods*
;
Open Fracture Reduction/methods*
;
Osteoporotic Fractures/surgery*
4.Clinical efficacy of robot-assisted single-position OLIF with lateral plate combined with posterior unilateral fixation for single-segment lumbar spinal stenosis.
Yuekun FANG ; Zhilin YANG ; Haotian LI ; Weizhou WANG ; Hangchuang BI ; Bing WANG ; Junjie DONG ; Jin YANG ; Zhiqiang GONG ; Lingqiang CHEN
Journal of Central South University(Medical Sciences) 2025;50(1):119-129
OBJECTIVES:
Oblique lateral interbody fusion (OLIF) has become a well-established treatment for lumbar spinal stenosis (LSS) due to its advantages of being minimally invasive, effective, and associated with fewer complications. However, relying solely on lateral fixation provides limited strength and uneven load distribution. Conventional posterior bilateral fixation after OLIF typically requires intraoperative repositioning, increases fluoroscopy frequency, and involves extensive dissection of posterior muscles and soft tissues, resulting in greater trauma, blood loss, and risks of dural tear, nerve root injury, and persistent postoperative low back pain. This study aims to compare the clinical efficacy of robot-assisted single-position OLIF with lateral plating and posterior unilateral fixation, OLIF with lateral fixation alone, and OLIF combined with posterior bilateral fixation for treating single-segment LSS, and to explore how to enhance fixation stability, reduce trauma, and achieve precise minimally invasive outcomes without changing patient positioning.
METHODS:
A retrospective analysis was conducted on the clinical data from patients treated for single-segment LSS between January 2020 and June 2023 at the First Affiliated Hospital of Kunming Medical University. Patients were divided into 3 groups: Robot group (robot-assisted single-position OLIF with lateral plate and posterior unilateral fixation, 33 cases), lateral group (OLIF with lateral fixation alone, 52 cases), and combined group (OLIF with posterior bilateral fixation, 45 cases). Surgical time, intraoperative blood loss, fluoroscopy frequency, hospital stay, pedicle screw placement accuracy, and complication rates were recorded. Pain visual analogue scale (VAS) scores and Oswestry disability index (ODI) scores were assessed preoperatively, postoperatively, and at the final follow-up. Radiological evaluations (X-ray, computed tomography, and magnetic resonance imaging) measured interbody disc height (IDH), intervertebral foraminal height (IFH), and cross-sectional area (CSA) of the dural sac. Differences between pre- and postoperative imaging indices were statistically analyzed, and complication rates, fusion rates, and cage subsidence rates were recorded.
RESULTS:
All patients exhibited good positioning of internal fixation devices and cages, with significant symptom relief and no cases of spinal cord injury or symptom worsening. The follow-up time was (15.2±3.6) months. The operation time of the robot group was (70.62±8.99) min, which was longer than that of the lateral group (45.90±6.09) min and shorter than that of the combined group (110.12±8.44) min. The intraoperative blood loss of the robot group was (44.27±6.87) mL, which was more than that of the lateral group (33.58±9.73) mL and less than that of the combined group (79.19±10.35) mL. The number of intraoperative fluoroscopy times of the robot group was (9.49±2.25), which was comparable to that of the lateral group (7.45±2.02) but less than that of the combined group (12.24±4.25). The hospital stay of the robot group was (9.28±2.10) days, which was longer than that of the lateral group (7.95±1.91) days and shorter than that of the combined group (12.49±5.07) days. The screw placement accuracy of the robot group was 98.48%, which was higher than that of the combined group (90.55%). Postoperative and final follow-up VAS and ODI scores were significantly lower than preoperative scores in all 3 groups (all P<0.05), and there were no significant differences in preoperative VAS and ODI scores among the groups (all P>0.05). Radiologically, IDH, IFH, and CSA at the surgical segment were significantly increased postoperatively and at final follow-up compared to preoperatively and at final follow-up compared to preoperative values (all P<0.05), with no significant differences among the groups postoperatively (all P>0.05). Internal fixation remained stable during the follow-up period, and all cages achieved fusion at final follow-up. The intervertebral fusion rate of the robot-assisted group was 93.40%, which was similar to that of the combined group (95.56%) and higher than that of the lateral approach group (90.34%). The complication rate of the robot-assisted group was 6.1%, which was comparable to that of the combined group (8.9%) and lower than that of the lateral approach group (15.4%) (P<0.05). No cases of fixation loosening or breakage were observed throughout the follow-up period.
CONCLUSIONS
Robot-assisted single-position OLIF with lateral plate combined with posterior unilateral fixation effectively achieves indirect decompression and excellent spinal stability without the need for intraoperative repositioning. It provides high pedicle screw accuracy, reduces intraoperative blood loss, fluoroscopy times, and complication rates, offering a fully minimally invasive new treatment option for single-segment LSS.
Humans
;
Spinal Stenosis/surgery*
;
Robotic Surgical Procedures/methods*
;
Lumbar Vertebrae/surgery*
;
Spinal Fusion/instrumentation*
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Aged
;
Treatment Outcome
;
Bone Plates
;
Minimally Invasive Surgical Procedures/methods*
;
Adult
5.Enhancing production of emestrin in Emericella sp. 1454 by adding the biosynthetic precursor glutathione
Yu-chuan CHEN ; Tong-mei XIAO ; Bing-jie SU ; Bi-ying YAN ; Li-yan YU ; Shu-yi SI ; Ming-hua CHEN
Acta Pharmaceutica Sinica 2024;59(4):1087-1091
Based on the genomic information of
6.Analysis of the clinical characteristics of acute myeloid leukemia related to the treatment of hematological and solid tumors
Yang JIAO ; Yanhong JIANG ; Bing LIU ; Ruihua MI ; Lijun BI ; Qingxia XU
Chinese Journal of Oncology 2024;46(1):86-95
Objective:To compare and analyze the clinical characteristics of acute myeloid leukemia (AML) related to the treatment of hematological tumors and solid tumors.Methods:The laboratory and clinical data of 41 patients with treatment-related AML (t-AML) in the Department of Hematology, Henan Cancer Hospital from January 2014 to December 2021 were retrospectively analyzed, and they were divided into hematological tumor group and solid tumor group. Survival analysis was performed using the Kaplan-Meier method and Log rank test.Results:The median interval from the first tumor diagnosis to t-AML in 41 patients was 21.0 (16.5-46.0) months; 24 (58.5%) had abnormal expression of lymphoid antigen, 28 (68.3%) had abnormal karyotype, 18 cases (43.9%) were positive for fusion gene, and 28 cases (68.3%) were positive for gene mutation; the median recurrence-free survival (RFS) was 11.0 months, and the median overall survival (OS) was 11.5 months. The proportion of acute promyelocytic leukemia ([APL], 0.0, 0/13), complete response ([CR],18.2%, 2/11), median OS (4.5 months) and median RFS (2.5 months) of t-AML patients in the hematological tumor group were significantly lower than those in the solid tumor group (35.7%, 10/28; 68.0%, 17/25; not reach; not reach), but the proportion of M4 /M5 (93.2%,12/13) was significantly higher than that in the solid tumor group (53.6%,15/18; all P values<0.05). Through subgroup analysis, the proportion of patients with positive PML-RARa and good prognosis karyotypes in the solid tumor group (35.7%, 10/28; 46.4%, 13/28) was significantly higher than that in the hematological tumor group (0.0, 0/13; 0.0, 0/13; P<0.05), while the proportion of patients with intermediate karyotypes (42.9%, 12/28) was significantly lower than that in the hematological tumor group (84.6%, 11/13; P<0.05), the difference was statistically significant. The CR rate (90.0%, 9/10), median OS (not reach) and median RFS (not reach) in the t-APL group were higher than those in the t-AML (without t-APL) group (38.5%, 10/26; 6 months; 8 months; P<0.05). After excluding the effect of t-APL patients, there was no significant difference in the CR rate, median OS and median RFS between the solid tumor group (8; 9 months; not reach) and the hematological tumor group (2; 4 months; 2 months; P>0.05). Univariate analysis showed that the primary tumor belongs to hematological tumor was a common risk factor for OS and RFS in t-AML patients ( P<0.10). Conclusions:Compared with patients with t-AML secondary to solid tumors, patients with t-AML secondary to hematological tumors have poorer treatment effects and poorer prognosis. After excluding the effect of t-APL patients, there are no significant differences in the treatment efficacy and prognosis between the two types of t-AML patients.
7.QU-Net application in retinal vessel segmentation based on hypercomplex numbers and U-Net
Bing LI ; Jie ZHANG ; Yanyu SHANGGUAN ; Qing JIANG ; Yunli NIU ; Yanlong BI
Chinese Journal of Experimental Ophthalmology 2024;42(12):1090-1099
Objective:To develop a U-Net-based quadruple numerical neural network (QU-Net) model for retinal vessel segmentation and to verify its precision and efficiency in extracting and segmenting retinal vessels from fundus images.Methods:This study used the concept of hypercomplex numbers, the three channels of color images, and a quaternion matrix representing all the information data of the images, which was then used as input for quaternion convolution and quaternion fully connected layers based on the U-Net architecture to form a QU-Net model.The QU-Net model was first tested on the DRIVE, STARE, and CHASE_DB1 datasets and compared with the traditional real-valued U-Net, M-Net, and SU-Net models in terms of accuracy, sensitivity, specificity, precision, F1 score, and Matthews correlation coefficient.Finally, the model was further optimized and the optimized QU-Net model was compared side-by-side with the well-known advanced models to comprehensively evaluate and analyze the efficiency and accuracy of the model in extracting and segmenting retinal blood vessels from fundus images.Results:The results showed that the QU-Net model achieved the following vessel segmentation results: accuracy 0.956 6, sensitivity 0.700 8, specificity 0.987 9, precision 0.595 4 on the DRIVE dataset, accuracy 0.975 5, sensitivity 0.890 7, specificity 0.984 2, precision 0.662 5 on the STARE dataset, and accuracy 0.979 4, sensitivity 0.747 0, specificity 0.990 6, precision 0.596 9 on the CHASE_DB1 dataset.Its specificity was better than U-Net, M-Net and SU-Net models, and its accuracy, sensitivity and precision were not inferior to the three models.After optimization, the sensitivity, precision and F1 value of the QU-Net model were effectively improved on the three datasets while maintaining its original accuracy and specificity.When compared with the performance indicators of other models on the three datasets, it was found that the optimized QU-Net model had good performance in accuracy, specificity, sensitivity, precision, and F1 score, indicating that its vessel segmentation ability was not inferior to the advanced models.Among all the models compared, the optimized QU-Net model had the best F1 score and Matthews correlation coefficient.Conclusions:The QU-Net model proposed in this study expands the data dimension space from the traditional real number space to the complex number space and greatly reduces the loss of data information.The optimized QU-Net model has good efficiency and accuracy in extracting retinal vessel segmentation from fundus images, and has certain advantages in detecting fine vessels.
8.Role of circTmeff-1 in morphine addiction memory of mice
Hailei YU ; Boyang WEN ; Yun LU ; Bing XIE ; Feng YU ; Minglong ZHANG ; Chunling MA ; Bin CONG ; Di WEN ; Haitao BI
Chinese Journal of Pharmacology and Toxicology 2023;37(7):539-540
In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.
9.Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma.
Zhao Gan REN ; Yu XU ; Zhan qiang HUA ; Zong Yi MO ; Luo Wen WANG ; Gen Bing SHI ; Wan Lin LIU ; Wei SUN ; Bi Qiang ZHENG ; Chun Meng WANG ; Yong Jia JIN ; Yong CHEN
Chinese Journal of Oncology 2023;45(11):973-980
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans
;
Antibodies, Monoclonal/therapeutic use*
;
Apoptosis
;
China
;
Disease-Free Survival
;
East Asian People
;
Immunotherapy
;
Interferon-alpha/therapeutic use*
;
Lymphatic Metastasis
;
Melanoma/pathology*
;
Programmed Cell Death 1 Receptor/therapeutic use*
;
Skin Neoplasms/pathology*
;
Melanoma, Cutaneous Malignant
10.Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma.
Zhao Gan REN ; Yu XU ; Zhan qiang HUA ; Zong Yi MO ; Luo Wen WANG ; Gen Bing SHI ; Wan Lin LIU ; Wei SUN ; Bi Qiang ZHENG ; Chun Meng WANG ; Yong Jia JIN ; Yong CHEN
Chinese Journal of Oncology 2023;45(11):973-980
Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans
;
Antibodies, Monoclonal/therapeutic use*
;
Apoptosis
;
China
;
Disease-Free Survival
;
East Asian People
;
Immunotherapy
;
Interferon-alpha/therapeutic use*
;
Lymphatic Metastasis
;
Melanoma/pathology*
;
Programmed Cell Death 1 Receptor/therapeutic use*
;
Skin Neoplasms/pathology*
;
Melanoma, Cutaneous Malignant

Result Analysis
Print
Save
E-mail