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Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis., Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology., Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm., Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Lu, Yang, Jiang, Zhang, Liu, Zhou, Li, Zeng, Long, Li, Du and Zhang.)

Introduction: Tientsin albino 2 (TA2) mice can develop spontaneous breast cancer (SBC), which is associated with multiple pregnancies and infection with the mouse mammary tumor virus (MMTV). In this study, we sought to elucidate the molecular mechanisms underlying the development of SBC in TA2 mice induced by MMTV., Methods: The integration site of MMTV in TA2 SBC was identified using whole-genome sequencing. The expression of fibroblast growth factor 3 (FGF3) in SBCs and normal breast tissues was compared. The primary cell line, TA-1106, derived from SBC, was cultured. The proliferation, cell cycle, migration, invasion, and tumorigenicity abilities, as well as the expression of epithelial-mesenchymal transition-related proteins, phosphorylated STAT3, and phosphorylated Akt, were assessed in MA-891cell line from TA2 and TA-1106 cells after FGF3 knockdown. The binding of FGF3 to FGF receptor 1 (FGFR1) was determined by co-immunoprecipitation. Additionally, the relationship between STAT3 and Akt phosphorylation was investigated using a small molecule inhibitor and STAT3 knockdown., Results: MMTV integrated upstream of the FGF3 gene, and the FGF3 protein was highly expressed in TA2 SBCs. FGF3 knockdown in MA-891 and TA-1106 decreased their proliferation, migration, and invasion abilities, affected the cell cycle and expression of epithelial-mesenchymal transition-related proteins, and inhibited the growth of animal xenografts. FGF3 binds to FGFR1, and either FGF3 or FGFR1 knockdown decreases STAT3 and Akt phosphorylation levels. Inhibition of phosphorylation or expression of STAT3 resulted in decreased Akt phosphorylation levels. Inhibition of Akt phosphorylation also resulted in decreased STAT3 phosphorylation levels. Furthermore, treatment of MA-891 and TA-1106 cells with Wortmannin or Stattic caused FGFR1 upregulation in addition to inhibiting Akt or STAT3 phosphorylation., Conclusion: The results of this study demonstrate that FGF3 plays a significant role in the development of SBC through the FGF3/FGFR1/STAT3 signaling pathway. There is a reciprocal activation between STAT3 and Akt. Inhibition of STAT3 or Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions obtained in this study in human breast cancer (HBC) may contribute to targeted therapy and it is worth exploring whether the homologous sequences of MMTV in HBC have a similar oncogenic effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhang, Liu, Chen, Zheng, Zhu and Zhang.)