Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

OBJECTIVETo explore the preoperative diagnostic value of ¹⁸F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (¹⁸F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis.

METHODSClinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent ¹⁸F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT were calculated.

RESULTSA total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign, of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%, 100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Kappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Kappa value -0.005, 0.305, 0.848). The area under curve(AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651(95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for ¹⁸F-FDG PET-ceCT respectively. The AUC of ¹⁸F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05).

CONCLUSION(18)F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.

Colorectal Neoplasms ; Contrast Media ; Fluorodeoxyglucose F18 ; Humans ; Liver Neoplasms ; Multimodal Imaging ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed

Objective To explore the preoperative diagnostic value of 18F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (18F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis. Methods Clinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent 18F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and 18F-FDG PET-ceCT were calculated. Results A total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign , of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT , ceCT and 18F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%,100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Κappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Κappa value -0.005, 0.305, 0.848). The area under curve (AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651 (95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for 18F-FDG PET-ceCT respectively. The AUC of 18F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05). Conclusion 18F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.

Objective To explore the preoperative diagnostic value of 18F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (18F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis. Methods Clinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent 18F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and 18F-FDG PET-ceCT were calculated. Results A total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign , of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT , ceCT and 18F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%,100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Κappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Κappa value -0.005, 0.305, 0.848). The area under curve (AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651 (95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for 18F-FDG PET-ceCT respectively. The AUC of 18F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05). Conclusion 18F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.