Supplementary figure 4. Spatial transcriptomics deciphers the immune landscape underlying diabetic pancreatic cancer. a. The relative mRNA expression of CXCL8, CXCL6, CCL20, CCL13 and CXCL9 in the tumor region between DM and Non-DM groups. b. The spatial expressions of C3 and HIST1H4J which are associated with neutrophil extracellular traps formation pathway at spatial level. c. The number of MPO + CitH3+ cells in field were calculated between DM and Non-DM groups (PDAC, n = 5, PDAC with DM, n = 5). d. Bar chart showing the percentage of 22 immune subgroups in PDAC. e. Bar chart showing cell proportions of 22 immune subgroups between PDAC and PDAC with DM groups. f. Spatial resolved gene expression images and expression level of N2-meutrophils between DM and non-DM groups.

Supplementary figure 5. DM promotes colorectal and breast cancer progression in mice models. a. Representative images and quantification of Ki-67 positive cells in tumor tissues by IHC (Scale bar = 50 µm, n = 6). b. Comparison of N2 polarized neutrophils between tumors obtained from DM and control groups using mIHC, scale bar = 50 μm. c. Experimental outline of murine subcutaneous colorectal cancer model. d. Representative images of tumor size. Scale bar represents 5 mm. The tumor volume and weight were compared. e. Growth curves of subcutaneous tumors. f. Representative immunofluorescence images and quantification of CD45+ Ly6g+ and MPO + CitH3+ cells in MC38 tumors (Scale bar = 100 µm, n = 5). Green, CD45 and CitH3 positive cell; Red, Ly6g and Mpo positive cell. g. Experimental outline of murine subcutaneous breast model. h. Representative images of subcutaneous breast tumors. Scale bar represents 5 mm. i. The tumor volumes and weight were compared. j. Representative immunofluorescence images and quantification of MPO + CitH3+ cells in the breast tumors (Scale bar = 100 µm, n = 5). k. Representative images of oil red staining in the SW1990 cells stimulated by high concentration of glucose (HG) versus normal glucose (NG). The levels of cholesterol in cellular supernatant were detected (n = 3). L. Flow cytometry gating strategy.

Supplementary figure 6. DM promotes PDAC progression through SREBP2-induced NETs formation. a. Western blot assay compared the protein level of SREBP2 between control and Betulin-treated tumor cells. The mRNA level of SREBP2 between control and Betulin-treated tumor cells. Comparison of cholesterol level in the supernatant of tumor cells between control and Betulin-treated tumor cells. b. The mRNA level of CXCL1 in the Pan02 cells following the inhibition of SREBP2 or cholesterol biosynthesis and the level of CXCL1 in the cellular supernatant (n = 3). c. The expression of CXCL1 in the tumors of control, betulin and simvastatin groups (Scale bar = 100 µm, n = 6). d. Levels of cholesterol within tumor tissues in different treatment conditions. e. WT and Pad4-/- mice were injected with STZ to induce diabetes. Mice were then injected with Pan02 cells and sacrificed 3 weeks after tumor implantation. Representative images (duplicates) of pancreatic orthotopic tumors. Scale bar represents 5 mm. The tumor volume and weight at the endpoint were compared. f. Representative immunofluorescence images and quantification of CD45+ Ly6g + cells in the tumors (Scale bar = 100 µm, n = 5). Green, CD45 positive cell; Red, Ly6g positive cell. g. Confirmation of SREBP2 knockdown in Pan02 cells determined by western blotting. h. Representative images of western blot and quantification of total and phosphorylation of NF-κB and AKT proteins in the pancreatic cells (SW 1990) stimulated by Betulin. i. The serum cholesterol between shNC and shSREBP2 groups. j. The levels of CXCL1 in the cellular supernatant of shNC and shSREBP2 groups (n = 5). The level of cholesterol in the shNC and shSREBP2 PAN02 cells (n = 3). k. The relative mRNA expression of CXCL1 and the cellular supernatant level of CXCL1 in Pan02 (shNC and shSREBP2) cells stimulated by NF-κB inhibitor (DHMEQ). l. The relative mRNA expression of CXCL1 and the cellular supernatant level of CXCL1 in Pan02 (shNC and shSREBP2) cells stimulated by AKT inhibitor (PI3K/AKT-IN-1).

Supplementary figure 7. Single cell sequencing revealed that DM promotes PDAC progression by increasing neutrophil infiltration. a. Schematic diagram showed the experimental design of multi-omics in diabetic PDAC progression. b. Heatmap plotting markers for all clusters. c. Pathway analysis from KEGG analysis showing metabolism-related pathways enriched by different genes in cancer cells between DM and Non-DM groups. d. The expression of CXCL1 in cancer cells. e. Functional enrichment of up-regulated genes in the cancer cells between DM and Non-DM groups. f. KEGG analysis showing the pathways enriched by up-regulated genes in neutrophils between DM and Non-DM groups.

Supplementary figure 3. The cluster analysis for spatial transcriptomics. a. Mapping of cell clusters to spatial locations in all samples. b. UMAP visualizing 15 clusters in all samples. Comparison of 15 spatial clusters between two groups using UMAP. c. Heatmap plotting markers for all clusters.

Supplementary Table 1. Characteristics of primary PDAC samples (HTAN) with diabetes status.

Supplementary figure 1. The prognostic implication of DM for pancreatic cancer. a. Forest plot showing the association between DM and the incidence of PDAC. b. Logistics analysis of potential predictors of development of PDAC.

Supplementary figure 2. Spatially resolved multi-omics reveals intratumor heterogeneity in PDAC. a. Graphic scheme of human cohorts used in this study. Strategy of integrated spatially resolved multi-omics for indicating PDAC metabolic remodeling and interactions under DM. b. Metabolites in the tumor area. c. OPLS-DA analysis indicating the clustering of all samples. d. MSEA analysis showing enriched metabolic pathways based on differential expressed metabolites in tumor-region.

BACKGROUND:Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β- catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway. METHODS:In vitro and in vivo models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β -catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity. RESULTS AND DISCUSSION:Hyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates in vitro, while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced. CONCLUSION:Hyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.

PURPOSE:Ovarian cancer is a heterogeneous solid tumor, whereas polycystic ovary syndrome (PCOS) is a distinct endocrine-metabolic ovarian disorder. Whether PCOS-associated ovarian dysregulation and ovarian cancer share convergent transcriptomic candidates remains unclear. This study aimed to identify shared transcriptomic candidates and define their cellular localization without implying a causal or clinical comorbidity relationship. MATERIALS AND METHODS:Public bulk transcriptomic datasets from PCOS and ovarian cancer underwent platform-specific preprocessing, within-disease-arm harmonization, differential-expression analysis, robust rank aggregation, and machine-learning-based feature prioritization with SHapley Additive exPlanations. Single-cell RNA sequencing datasets were used to localize prioritized genes in PCOS-related ovarian cell populations and high-grade serous ovarian cancer (HGSOC)-derived compartments. Preliminary validation used DHEA-treated KGN cells and siRNA-mediated SIX4 knockdown in SKOV3 cells. Exploratory docking and molecular dynamics simulation assessed the structural tractability of a SIX4-centered axis. RESULTS:Integrated analysis identified shared molecular dysregulation enriched in cell-cycle regulation, chromosome segregation, epithelial remodeling, and Wnt-related pathways. Five candidate genes were prioritized: SIX4, CCNE1, MMP7, KIF2C, and GPX3. SIX4 was the highest-ranked contributor within the computational model. Single-cell analysis showed compartment-specific localization, with SIX4 enriched in HGSOC-derived epithelial populations. DHEA increased SIX4 expression in KGN cells, whereas SIX4 knockdown suppressed SKOV3 proliferation, migration, and colony formation. Molecular dynamics suggested stable predicted engagement between SIX4 and a Benzbromarone-related scaffold. CONCLUSION:This study identifies SIX4 as a candidate epithelial target in ovarian cancer within a shared, noncausal transcriptomic program associated with PCOS-related ovarian dysregulation.

The phase 3 COMPASSION-16 trial demonstrates significant progression-free survival (PFS) and overall survival (OS) benefits with cadonilimab plus standard therapy in patients with persistent, recurrent, or metastatic cervical cancer. This analysis aims to assess efficacy outcomes in patient subgroups of COMPASSION-16. The dual primary endpoints of COMPASSION-16 are PFS, assessed by the blinded independent central review (BICR) according to RECIST version 1.1, and OS. The secondary endpoint is objective response rate. In this subgroup analysis, the PFS, OS and objective response rate are evaluated in subgroups including bevacizumab use, prior concurrent chemoradiotherapy, PD-L1 combined positive score (CPS), metastatic disease at baseline, platinum use, and age. With median follow-up of 25.6 months, hazard ratios (HRs) for PFS favour cadonilimab group in all subgroups. Moreover, the addition of cadonilimab is also associated with prolonged overall survival. This subgroup analysis confirms that improvements in progression-free and overall survival are consistent with the primary results of the COMPASSION-16 study across diverse patient profiles.

Premature ovarian insufficiency (POI) poses a significant threat to female reproductive health and currently lacks effective interventions. Recent studies highlight the promising potential of human pluripotent stem cell-derived mesenchymal stem cells (hPSC-MSC) in regenerative medicine. However, research on hPSC-MSC-based treatments for POI remains limited, particularly in the characterization of the intermediate differentiation stages from hPSC to MSC. This study presents an accelerated differentiation protocol for generating hPSC-MSC via neural crest cells (NCC) and evaluates their therapeutic potential in chemotherapy-induced POI. We modified a canonical small molecule-mediated protocol for hPSC-NCC-MSC differentiation. Systematic characterization of differentiated-cells was performed using qPCR, immunofluorescence, cell viability assays, flow cytometry and trilineage differentiation. In vivo, hPSC-NCC-MSC were transplanted into chemotherapy-induced POI SD rat models, and parameters such as body weight, ovarian weight, estrous cycle, hormone levels, follicle count, and mating were assessed. Granulosa cells (GC) apoptosis was analyzed using TUNEL assay and immunohistochemistry. In vitro, their effects on apoptosis inhibition and oxidative stress alleviation were investigated in a cultured GC cell line. Additionally, comparisons between umbilical cord MSC (UC-MSC) and hPSC-NCC-MSC in chemotherapy-induced POI was conducted. Our optimized protocol, combining CHIR99021 and SB431542, efficiently induced NCC from both human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC). The programmed hPSC-NCC-MSC, characterized by specific NCC markers (P75, HNK1, SOX10, and AP2α), exhibited typical MSC morphology, trilineage differentiation potential, favorable cell viability, and prominent anti-senescence properties. Among these, NCC differentiated from H1-hESCs (H1-NCC) demonstrated the highest induction efficiency (72.45

Take-home message:This Chinese expert consensus focuses on the hematoporphyrin derivative(HpD)photodynamic therapy(PDT)in cervical high-grade squamous intraepithelial lesion(HSIL).It aims to provide systematic guidance for gynaecolo-gists,oncologists,nursing professionals and PDT practitioners at all levels in the clinical application of HpD-PDT for the treatment of cervical HSIL.

Introduction: N-acetyltransferase 10 (NAT10) mediates N4-acetylcytidine (ac4C) mRNA modification and promotes malignant tumor progression. However, there has been limited research on its role in cervical cancer. This study aimed to decipher the role of NAT10 in cervical cancer. Methods: The prognostic value of NAT10 was explored using the cancer genome atlas (TCGA) database and immunohistochemistry of cervical cancer tissue. The biological actions of NAT10 in cervical cancer were investigated by cell proliferation, transwell, wound healing, and chicken chorioallantoic membrane assays. The therapeutic action of remodelin (a NAT10 inhibitor) was verified in a nude mouse model. Mechanistic analyses were conducted by RNA sequencing, ac4C dot blotting, acetylated RNA immunoprecipitation, quantitative PCR, and RNA stability experiments. Results: NAT10 was overexpressed in cervical carcinoma and its overexpression was associated with poor prognosis. NAT10 knockout impaired proliferative and metastatic potentials of cervical cancer cells, while its overexpression had the opposite effects. Remodelin impaired cervical cancer proliferation in vivo and in vitro. NAT10 acetylated solute carrier family 7 member 5 (SLC7A5) enhanced mRNA stability to regulate SLC7A5 expression. Conclusions: NAT10 exerts a critical role in cervical cancer progression via acetylating SLC7A5 mRNA and could represent a key prognostic and therapeutic target in cervical cancer.

5509 Background: The phase 3 COMPASSION-16 trial demonstrated statistically significant progression-free survival (PFS) and overall survival (OS) benefits with cadonilimab plus chemotherapy ± bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer (R/M CC). This analysis assessed efficacy in several key clinical subgroups. Methods: R/M CC pts who had no prior systemic treatment were randomized 1:1 to receive cadonilimab (10 mg/kg) or placebo Q3W plus platinum-based chemotherapy ± bevacizumab (15 mg/kg). The dual primary endpoints were PFS per RECIST v1.1 assessed by blind independent central review and OS in the ITT population. Treatment effects on PFS and OS were evaluated in subgroups including age (<65 or ≥65 years), bevacizumab use (yes or no), prior concurrent chemoradiotherapy (CCRT; yes or no), metastatic disease at baseline (yes or no), PD-L1 CPS (<1, ≥1, or ≥10), and platinum use (cisplatin or carboplatin). Hazard ratios (HRs) and 95% CIs were estimated from an unstratified Cox model. Results: 445 patients were randomized (222 to the cadonilimab group and 223 to the placebo group). At the Apr 30, 2024 data cutoff, the median follow-up was 26 months. The addition of cadonilimab prolonged PFS and OS in all investigated subgroups (Table). Conclusions: Subgroup analyses of COMPASSION-16 showed that the addition of cadonilimab to chemotherapy ± bevacizumab improved PFS and OS across subgroups defined by age, bevacizumab use, prior CCRT, metastatic disease, PD-L1 CPS, and platinum use, consistent with results for the overall population. Cadonilimab plus standard treatment is a potential treatment option for patients with R/M CC. Clinical trial information: NCT04982237 . Subgroup (N) Median PFS (mo)Cadonilimab Median PFS (mo)Placebo PFS, HR (95% CI) Median OS (mo)Cadonilimab Median OS (mo)Placebo OS, HR (95% CI) <65 yrs (369) 13.5 9.5 0.68 (0.52, 0.88) NR 25.3 0.69 (0.50, 0.95) ≥65 yrs (74) 12.0 7.4 0.39 (0.22, 0.68) 26.6 15.5 0.49 (0.27, 0.91) With bevacizumab (265) 15.1 11.5 0.78 (0.57, 1.06) NR NR 0.84 (0.56, 1.26) Without bevacizumab (180) 11.7 6.7 0.44 (0.31, 0.63) 28.8 15.1 0.50 (0.33, 0.75) CCRT, yes (215) 16.1 7.9 0.55 (0.39, 0.78) NR 22.8 0.54 (0.35, 0.82) CCRT, no (230) 12.0 8.5 0.67 (0.49, 0.93) 27.0 24.5 0.76 (0.52, 1.12) Metastatic, yes (323) 12.0 8.3 0.70 (0.54, 0.92) 28.8 25.3 0.73 (0.52, 1.02) Metastatic, no (122) NR 8.0 0.42 (0.25, 0.70) NR 17.6 0.48 (0.27, 0.86) PD-L1 CPS<1 (116) 12.0 8.2 0.65 (0.42, 1.03) NR 25.3 0.77 (0.44, 1.34) PD-L1 CPS≥1 (312) 14.7 8.3 0.62 (0.47, 0.83) NR 22.7 0.69 (0.49, 0.97) PD-L1 CPS≥10 (180) 17.1 8.1 0.54 (0.37, 0.79) NR 29.0 0.68 (0.42, 1.08) Cisplatin (192) 14.7 8.1 0.49 (0.34, 0.72) NR 23.9 0.43 (0.27, 0.70) Carboplatin (253) 12.0 8.2 0.72 (0.53, 0.97) 27.8 22.8 0.82 (0.57, 1.18)

Background:This study evaluated the prognostic value of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score for postoperative recurrence in endometrial cancer patients. A nomogram was developed based on clinicopathological parameters, HALP score, and immunohistochemical markers to predict recurrence-free survival (RFS) in patients with stage I-III endometrial cancer. Methods:This retrospective study included 1,083 patients who underwent hysterectomy at the First Affiliated Hospital of Chongqing Medical University from January 2013 to January 2021. Independent risk factors for RFS were identified using univariate and multivariate Cox regression analyses, and a nomogram was established. External validation was performed with data from Zhujiang Hospital of Southern Medical University and Women and Children's Hospital of Chongqing Medical University (n = 677). Results:Among the entire cohort, 241 cases (13.7%) of endometrial cancer experienced recurrence post-hysterectomy. The median RFS time was 47.0 (range: 6.0-91.0) months. Eleven independent prognostic factors were identified, including age, FIGO staging, histologic type, myometrial invasion, lymphovascular space invasion, Ca125, Ki-67 expression, ER expression, molecular classification, adjuvant therapy, and HALP score, and then a nomogram for predicting recurrence of endometrial cancer was established. The nomogram demonstrated improved predictive accuracy, categorizing patients into high- and low-risk groups. High-risk patients receiving adjuvant treatment had better outcomes than those who did not. Conclusion:We developed and validated a nomogram to predict recurrence in endometrial cancer patients. Integrating the HALP score can help clinicians identify high-risk patients and tailor personalized treatment strategies.

2611 Background: BAT1308 is a fully humanized and high-affinity anti-PD-1 IgG4κ antibody. Previous phase 1 study demonstrated BAT1308 had a promising efficacy in patients with advanced cervical cancer. Here we present the primary safety and efficacy results in phase 2 study for BAT1308 combined with platinum-based chemotherapy ± bevacizumab as first-line therapy for PD-L1–positive persistent, recurrent, or metastatic cervical cancer. Methods: In this multicenter, single-arm, open-label, phase 2 study, eligible patients were ≥18 to ≤75 years of age with PD-L1 CPS ≥1, FIGO Stage IVB cervical cancer, who did not receive prior systemic anti-tumor therapy for persistent, recurrent or metastatic cervical cancer and not amenable to curative treatment. Patients received BAT1308 (300 mg Q3W for up to 24 months) plus platinum-based chemotherapy (paclitaxel 175 mg/m 2 + cisplatin 50 mg/ m 2 or carboplatin AUC 5) and, per investigator discretion, bevacizumab (15 mg/kg). The primary endpoint was safety. The major secondary endpoint was objective response rate assessed by investigator according to RECIST 1.1. Results: As of January 7, 2025, a total of 29 patients were enrolled, with a median age of 53 years (range 32-69), 20 (69.0%) patients had ECOG performance status of 1, 15 (50.7%) patients with PD-L1 CPS ≥ 10, 24 (82.8%) patients had squamous-cell carcinoma, 17 (58.6%) patients received previous neoadjuvant or adjuvant chemotherapy or chemoradiotherapy with a paclitaxel + platinum regimen, 7 (24.1%) patients had previous untreated metastatic disease at trial entry. Bevacizumab was used by 23 (79.3%) patients in this phase II study. All 29 subjects received combination therapy. 27 subjects completed at least one efficacy assessment. The ORR was 74.1%, with a confirmed ORR of 70.4%. The complete response rate was 11.1%, and the disease control rate was 100%. Currently, 16 subjects remain on treatment. Among those who discontinued the study, 8 withdrew informed consent, 4 experienced disease progression, and 1 died. The 6-month, 9-month, and 12 -month PFS rates were 83.4%, 78.8%, and 78.8% respectively. The median PFS has not yet been reached. The most common adverse events were anemia (82.8%), white blood cell decreased (51.7%), alopecia (51.7%), thrombocytopenia (48.3%), and neutropenia (44.8%). Grade 3 and above adverse events occurred in 72.4% of 29 patients, and ≥ Grade 3 irAEs observed in 3 (10.3%) patients. Serious adverse events occurred in 44.8% of the patients. Conclusions: BAT1308 combined with platinum-based chemotherapy ± Bevacizumab as first-line therapy showed durable anti-tumor activity and manageable safety profile for PD-L1-positive (CPS ≥ 1) persistent, recurrent or metastatic cervical cancer. These data are consistent with the earlier results and provide support for further studies. Clinical trial information: NCT06123884 .

Cesarean section (CS) is highly prevalent surgery among females. However, current absorbable anti-adhesion membranes used clinically can partially prevent postoperative adhesions but show limited efficacy in tissue regeneration, leaving post-cesarean women at risk for severe complications including cesarean scar pregnancy, placenta previa, and uterine rupture. Herein, we designed a fully amniotic membrane (AM)-derived biomimetic nanostructural materials (AM-BNMs) as an anti-adhesion barrier, and validated its therapeutic efficacy in a rat CS model. The biomaterial consisted of AM-extracellular matrix (ECM) nanofibers, enriched with hemostatic proteins (collagen, S100A8, S100A9, etc.), carrying AM mesenchymal stem cells (MSCs)-secretome that exhibited significantly elevated levels of pro-regenerative factors (miR-302a-3p, angiogenin, VEGF, etc.) compared to endogenous secretion. The reconstituted AM-BNMs demonstrated synergistic effects at CS wounds, effectively preventing adhesion formation while promoting hemostasis and tissue regeneration. In summary, this readily accessible human-derived biomaterial shows promising potential in preventing adhesion-related complications and enhancing uterine wound healing, thereby promoting female reproductive health.

BACKGROUND:Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS:In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS:445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION:The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING:Akeso Biopharma.

Choriocarcinoma (CC) is a rare and highly malignant epithelial tumour. However, the mechanism underlying its occurrence and development remains unknown. We aimed to reveal the biological significance and prognostic value of Claudin-6 (CLDN6) in gestational trophoblastic disease (GTD). We collected clinical GTD specimens from 2011 to 2019 and measured CLDN6 gene expression by immunohistochemistry (IHC). High-throughput mRNA sequencing (RNA-seq) revealed a GTD progression-associated gene. CCK-8, wound healing, and flow cytometry assays were used to assess the biological effects of CLDN6 overexpression and knockdown. The medical records of 118 GTD patients from 2011 to 2019 were retrospectively analysed to identify correlations between CLDN6 expression and GTD patient clinical–pathological parameters; these correlations were analysed using the chi-square test and one-way ANOVA. Univariate logistic regression was used to analyse various prognostic parameters of patients with post-molar GTN. CLDN6 had the second highest fold change in gene expression between GTN and normal samples. CLDN6 was highly expressed in GTN tissues and CC cell lines, and silencing CLDN6 inhibited the proliferation and migration and promoted the apoptosis of CC cells. CLDN6 overexpression was significantly correlated with uterine size (p = 0.01) and ovarian cysts > 6 cm (p = 0.027), CLDN6 expression was significantly higher in HR-GTNs than in low-risk GTNs (LR-GTNs) (p = 0.008), and logistic regression analysis showed that CLDN6 expression in hydatidiform moles (HMs) was related to a high risk of developing post-molar GTN (OR = 2.393, p = 0.03). We propose that CLDN6 participates in the development of GTD and may become a new therapeutic target for CC.