Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz-Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 and Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11-Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11-Cre/ERT2 mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1-Cd44 or Spp1-Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2-3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.

UNASSIGNED: Gastrointestinal polyps are common gastrointestinal diseases that involve localised hyperplastic masses derived from gastrointestinal mucosa.
UNASSIGNED: To investigate the risk factors of delayed post-polypectomy bleeding (DPPB) after the treatment of gastrointestinal polyps with snare-assisted endoscopic sub-mucosal dissection (ESD) and to construct a nomogram model to predict the risk of DPPB.
UNASSIGNED: A total of 226 patients who underwent snare-assisted ESD for gastrointestinal polyps from May 2018 to November 2020 were divided into DPPB group (n = 10) and non-DPPB group (n = 216).
UNASSIGNED: The correlations of clinical data and endoscopic data with DPPB were compared. Univariate analysis was performed to screen the influencing factors of DPPB. Multivariate logistic regression analysis was used to screen the risk factors of DPPB, which was employed to construct a nomogram prediction model.
UNASSIGNED: SPSS 16.0 software was utilised for statistical analysis. Numerical data were expressed as percentage (n [%]), and Chi-square test was performed for univariate analysis. The significant factors (P < 0.05) in univariate analysis were included in multivariate logistic regression analysis, and the variables with statistical significance (P < 0.05) were considered as independent risk factors. The factors were used to construct a nomogram model for predicting the risk of DPPB. Bootstrap method was employed to perform repeated sampling 1000 times for internal verification. The consistency index (C-index) was used to evaluate the discrimination of the model, and C-index ≥0.70 represented a good discrimination. Two-tailed P < 0.05 indicated that a difference was statistically significant.
UNASSIGNED: Univariate and multivariate logistic regression analyses revealed that hypertension, polyp location, polyp diameter, polyp morphology and intra-operative bleeding were the independent risk factors for DPPB (P < 0.05). The C-index of the nomogram model for predicting the risk of DPPB was 0.791, indicating a good discrimination. The calibration curve showed that the mean absolute error between predicted and actual DPPB occurrence risks was 0.014, indicating a high accuracy.
UNASSIGNED: Hypertension, polyp location, polyp diameter, polyp morphology and intra-operative bleeding are the independent risk factors for DPPB, and the nomogram model established based on these factors for prediction has good discrimination and accuracy. Therefore, it is recommended to perform targeted intervention for high-risk groups to reduce the incidence of DPPB.

Peutz-Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 (STK11)/ liver kinase B1 (LKB1) gene-related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro-intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post-resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non-gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS-associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS-associated polyps. Other features include focal depigmentation followed by hyperpigmentation, and xeroderma pigmentosum-like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The STK11 gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex-cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS-SCTAT vs. non-PJS-SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30-40% of LCCSCTs are caused by PJS or Carney complex. PJS-LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro-calcifications. Testicular, intra-tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia.