1.Small nucleolar RNA host gene 1 (SNHG1) facilitates gemcitabine chemosensitivity in gallbladder cancer by regulating the miR-23b-3p/phosphatase and tensin homolog (PTEN) pathway.
Hui WANG ; Yixiang GU ; Miaomiao GUO ; Ming ZHAN ; Min HE ; Yang ZHANG ; Linhua YANG ; Yingbin LIU
Chinese Medical Journal 2025;138(21):2783-2792
BACKGROUND:
Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance.
METHODS:
To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1.
RESULTS:
Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine.
CONCLUSION
The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans
;
Deoxycytidine/pharmacology*
;
PTEN Phosphohydrolase/genetics*
;
Gemcitabine
;
RNA, Long Noncoding/metabolism*
;
MicroRNAs/genetics*
;
Gallbladder Neoplasms/genetics*
;
Cell Line, Tumor
;
Animals
;
Mice
;
Drug Resistance, Neoplasm/genetics*
;
Mice, Nude
;
Antimetabolites, Antineoplastic
;
Gene Expression Regulation, Neoplastic
2.Targeted therapies and immunotherapies for unresectable cholangiocarcinoma.
Shengbai XUE ; Weihua JIANG ; Jingyu MA ; Haiyan XU ; Yanling WANG ; Wenxin LU ; Daiyuan SHENTU ; Jiujie CUI ; Maolan LI ; Liwei WANG
Chinese Medical Journal 2025;138(16):1904-1926
Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans
;
Cholangiocarcinoma/drug therapy*
;
Immunotherapy/methods*
;
Bile Duct Neoplasms/drug therapy*
;
Molecular Targeted Therapy/methods*
3.Expert consensus on conversion therapy of biliary tract cancer (2025).
Chinese Journal of Surgery 2025;63(6):453-460
Most patients with biliary tract cancer are diagnosed at advanced stage and lose the opportunity for radical surgery,resulting in dismal prognosis. In recent years,with advances in therapeutic approaches,conversion therapy has gradually been implemented in some cases of initially unresectable biliary tract cancer, enabling a subset of patients to achieve opportunities for curative surgery. To further standardize conversion therapy of biliary tract cancer and improve the overall efficacy, the Branch of Biliary Surgery, Chinese Society of Surgery, Chinese Medical Association and Working Group of Biliary Surgeons,Chinese College of Surgeons,Chinese Medical Doctor Association, based on the latest evidence-based medical evidence and specific practices in the treatment of biliary tract cancer in China,organized discussion among experts in the field. Following the discussion,the "Expert consensus on conversion therapy of biliary tract cancer(2025)" was developed. This consensus aims to address key issues in the field of biliary tract cancer conversion therapy, standardize diagnostic and therapeutic procedures and protocols, and lay the foundation for further advancing research and practice in this area.
Humans
;
Biliary Tract Neoplasms/surgery*
;
Consensus
4.Expert consensus on lymph node dissection for intrahepatic cholangiocarcinoma(2025).
Chinese Journal of Surgery 2025;63(7):541-545
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with poor prognosis, and lymph node metastasis constitutes one of the critical risk factors contributing to unfavorable patient outcomes. Lymph node dissection holds significant value in accurately staging ICC, guiding prognostic evaluation, and determining adjuvant therapeutic strategies. In recent years, both domestic and international scholars have conducted extensive research on lymph node metastasis and dissection in ICC. However, discrepancies persist among various research findings and consensus guidelines domestically and internationally regarding the understanding and recommendations for lymph node dissection in ICC. Furthermore, substantial variations exist in the extent of lymph node dissection, the minimum number of lymph nodes required for retrieval, and surgical dissection techniques, which have consequently led to divergent research conclusions. To standardize the clinical practice of lymph node dissection for ICC in China and enhance the level of ICC diagnosis and treatment, the Branch of Biliary Surgery, Chinese Society of Surgery, Chinese Medical Association and Working Group of Biliary Surgeons, Chinese College of Surgeons, Chinese Medical Doctor Association, convened relevant experts to develop this expert consensus. This consensus document has been formulated based on the latest evidence-based medical research and accumulated clinical experience.
Humans
;
Cholangiocarcinoma/pathology*
;
Lymph Node Excision
;
Bile Duct Neoplasms/pathology*
;
Lymphatic Metastasis
;
Consensus
;
Prognosis
5.Multi-Phase Contrast-Enhanced CT Clinical-Radiomics Model for Predicting Prognosis of Extrahepatic Cholangiocarcinoma After Surgery: A Single-Center Retrospective Study.
Shen-Bo ZHANG ; Zheng WANG ; Ge HU ; Si-Hang CHENG ; Zhi-Wei WANG ; Zheng-Yu JIN
Chinese Medical Sciences Journal 2025;40(3):161-170
OBJECTIVES:
To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection.
METHODS:
In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index).
RESULTS:
This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616).
CONCLUSIONS
The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Cholangiocarcinoma/mortality*
;
Prognosis
;
Bile Duct Neoplasms/mortality*
;
Tomography, X-Ray Computed/methods*
;
Aged
;
Radiomics
6.Research Progress of Chinese Medicine Monomers in Treatment of Cholangiocarcinoma.
Xiang WANG ; Xiao-Qing WANG ; Kai LUO ; He BAI ; Jia-Lin QI ; Gui-Xin ZHANG
Chinese journal of integrative medicine 2025;31(2):170-182
Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy*
;
Humans
;
Drugs, Chinese Herbal/pharmacology*
;
Bile Duct Neoplasms/drug therapy*
;
Medicine, Chinese Traditional
;
Animals
;
Signal Transduction/drug effects*
7.Acquired hemophilia A secondary to cholangiocarcinoma: A case report and literature review.
Xiaoting HAN ; Lei FU ; Liang LI ; Jianjun BIAN ; Mei ZHAO ; Guobin BI
Journal of Central South University(Medical Sciences) 2025;50(2):275-280
Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Its occurrence secondary to hepatobiliary malignancies is even rarer, and without timely diagnosis and treatment, the mortality rate is extremely high. There is a need to raise awareness of this disease. This report describes a case of a 70-year-old female patient diagnosed with AHA 2 months after surgery for cholangiocarcinoma, admitted to the Second Affiliated Hospital of Bengbu Medical College in October 2022. The patient presented with subcutaneous hematoma in both lower limbs. Coagulation function tests showed a markedly prolonged activated partial thromboplastin time (APTT) of 74.5 seconds, with no correction in the APTT mixing test. Coagulation factor assays revealed a severely reduced coagulation factor VIII activity (FVIII:C) of 0.3%, and an inhibitor titer of 25.6 BU/mL was detected. After ruling out other potential causes, the patient was diagnosed with cholangiocarcinoma-associated AHA. With chemotherapy to control the primary tumor, alongside hemostatic and immunosuppressive therapy for inhibitor eradication, AHA was brought under control. The patient had no further coagulation abnormalities or bleeding, enabling timely and full-course chemotherapy for cholangiocarcinoma and significantly improving survival and quality of life. Therefore, in patients with malignancies who present with spontaneous bleeding or unusual bleeding following surgery, trauma, or invasive procedures, clinicians should be alert to the possibility of secondary AHA. Timely diagnosis and treatment can significantly improve prognosis.
Humans
;
Cholangiocarcinoma/surgery*
;
Female
;
Hemophilia A/drug therapy*
;
Aged
;
Bile Duct Neoplasms/surgery*
;
Factor VIII
8.Precision medicine for advanced biliary tract cancer in China: current status and future perspectives.
Zhen HUANG ; Wen ZHANG ; Yongkun SUN ; Dong YAN ; Xijie ZHANG ; Lu LIANG ; Hong ZHAO
Frontiers of Medicine 2025;19(5):743-768
Biliary tract cancer (BTC) is a rare group of malignancies that develop from the epithelial lining of the biliary tree and have a poor prognosis. Although chemotherapy is the standard of care for patients with advanced BTC in China, its clinical benefits are moderate. In recent years, the approval of targeted therapies and immunotherapies has provided new avenues for the management of advanced BTC. Nonetheless, the increasing number of personalized medicine approaches has created a challenge for clinicians choosing individualized treatment strategies based on tumor characteristics. In this article, we discuss recent progress in implementing precision medicine approaches for advanced BTC in China and examine genomic profiling studies in Chinese patients with advanced BTC. We also discuss the challenges and opportunities of using precision medicine approaches, as well as the importance of considering population-specific factors and tailoring treatment approaches to improve outcomes for patients with BTC. In addition to providing a comprehensive overview of current and emerging precision medicine approaches for the management of advanced BTC in China, this review article will support clinicians outside of China by serving as a reference regarding the role of patient- and population-specific factors in clinical decision-making for patients with this rare malignancy.
Humans
;
Precision Medicine/methods*
;
Biliary Tract Neoplasms/genetics*
;
China
;
Molecular Targeted Therapy
;
Immunotherapy/methods*
10.Disease burden of biliary tract cancer in 204 countries and territories, 1990-2021: A comprehensive demographic analysis of the Global Burden of Disease Study 2021.
Xuheng SUN ; Jiangmei LIU ; Wei ZHANG ; Yijun WANG ; Yan JIANG ; Lijun WANG ; Yixin ZOU ; Yuxuan XIAO ; Yongbing XIANG ; Maolan LI ; Maigeng ZHOU ; Yingbin LIU
Chinese Medical Journal 2024;137(24):3117-3125
BACKGROUND:
Biliary tract carcinomas (BTCs) are relatively rare but lethal primary malignant tumors derived from the biliary tract system. The burden of BTCs varies according to sex, age, region, and country, but limited attention has been paid to the burden of BTCs. We sought to explore the up-to-date data from the Global Burden of Disease Study (GBD) and expand findings by accessing the demographic features of BTC disease burden.
METHODS:
Using the latest data from the GBD 2021, we evaluated and analyzed the distributions and patterns of BTC disease burden in various age groups, sexes, regions, and countries.
RESULTS:
The number of incident cases, deaths, and disability-adjusted life-years (DALYs) tended to increase and peaked at 216,770 (95% uncertainty interval [UI]: 181,890-245,240), 171,960 (95% UI: 142,350-194,240), and 3,732,100 (95% UI: 3,102,900-4,317,000) person-years, respectively, in 2021. However, the average global age-standardized rates (ASRs) of incident cases, deaths, and DALYs shrunk by -11.46% (95% UI: -21.91 to 3.35%), -24.09% (95% UI: -33.19 to 16.88%), and -26.25% (95% UI: -35.53 to 18.36%), respectively, from 1990 to 2021. Meanwhile, the male/female ratio (male per 100 female) of incidence, deaths, and DALYs changed from 76.40, 75.41, and 74.72 to 86.89, 79.11, and 82.29, respectively. In 2021, the highest number of incident cases, deaths, and DALYs occurred in East Asia. The top three highest incidences, deaths, and DALYs were observed in China, India, and Japan, and the highest ASRs were observed in Chile in 2021. Analysis of the Human Development Index along with disease burden estimates of BTCs also suggests that the burden of the disease is related to the level of comprehensive development of the society.
CONCLUSION
This study provided a comprehensive comparison of differences in the burden of disease across populations and over time, and further presented evidence concerning the formulation of prevention and control policies and etiologic studies for BTCs and proposed logical hypotheses to investigate.
Humans
;
Global Burden of Disease
;
Biliary Tract Neoplasms/epidemiology*
;
Male
;
Female
;
Disability-Adjusted Life Years
;
Middle Aged
;
Aged
;
Adult
;
Incidence
;
Aged, 80 and over
;
Quality-Adjusted Life Years
;
Cost of Illness

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