The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objective To investigate the clinical features and risk factors of primary biliary cholangitis(PBC)comorbid with metabolic associated fatty liver disease(MAFLD)and the interaction between the two diseases.Methods A total of 187 patients who were diagnosed with PBC,MAFLD,or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients,PBC+MAFLD group with 38 patients,and MAFLD group with 79 patients.Related data were collected,including general information,clinical symptoms,serological parameters,transient elastography(FibroScan),and non-invasive fibrosis markers,which were compared between the three groups.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups,the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups,and the binary Logistic regression analysis was used for multivariate analysis.Results There were significant differences between the three groups in sex,age,height,weight,body mass index(BMI),and history of autoimmune diseases(P<0.05).In the PBC+MAFLD group,female patients accounted for 89.5%,with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m2,and in the PBC group,the detection rate of autoimmune diseases was 25.7%(18 patients).There were significant differences between the three groups in the incidence rates of weakness,poor appetite,pruritus,jaundice,varices,ascites,and splenomegaly(all P<0.05).The PBC+MAFLD group had the common symptoms of weakness in 18 patients(47.4%),poor appetite in 15 patients(39.5%),abdominal pain in 14 patients(36.8%),and abdominal distension in 16 patients(42.1%);the MAFLD group had the common symptoms of abdominal pain in 34 patients(43%)and abdominal distension in 32 patients(40.5%);the PBC group had the common symptoms of weakness in 37 patients(52.9%),poor appetite in 25 patients(35.7%),jaundice in 25 patients(35.7%),abdominal pain in 18 patients(25.7%),abdominal distension in 25 patients(35.7%),varices in 19 patients(27.9%),ascites in 23 patients(32.9%),and splenomegaly in 44 patients(62.9%).The PBC+MAFLD group had a controlled attenuation parameter(CAP),which was higher than that of the PBC group,and the PBC group had significantly higher levels of liver stiffness measurement,aspartate aminotransferase-to-platelet ratio index(APRI),and fibrosis-4(FIB-4)than the MAFLD group(all P<0.05).The factors without multicollinearity were included in the regression analysis,and with the PBC group as the reference group,FIB-4(odds ratio[OR]=0.218,95%confidence interval[CI]:0.069-0.633,P<0.05)and history of autoimmune diseases(OR=0.229,95%CI:0.067-0.810,P<0.05)were influencing factors for the onset of PBC with MAFLD;with the MAFLD group as the reference group,ALT(OR=0.157,95%CI:0.025-1.000,P<0.05)and TBil(OR=0.995,95%CI:0.990-0.999,P<0.05)were influencing factors for the onset of PBC with MAFLD.Conclusion PBC with MAFLD lacks specific clinical manifestations,and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation.PBC comorbid with MAFLD may not aggravate the disease progression of PBC.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*