About

Jin Xu is an Associate Professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin School of Medicine and Public Health. He holds an MD and MS degree and is based at the University of Wisconsin Hospital and Clinics, with a focus on pathology. His residency training includes Anatomical and Clinical Pathology at UW-Madison, and his fellowship training encompasses General Surgical Pathology at UW-Madison and Breast Pathology at Memorial Sloan Kettering Cancer Center in New York. His clinical interests are centered on breast and gynecologic surgical pathology, and his research interests include biomarkers in breast pathology and the role of beta-catenin in gynecological tumors. Dr. Xu has contributed to numerous publications in the field, exploring topics such as high-grade endometrioid adenocarcinoma, ovarian endometrioid adenocarcinomas, and breast cancers with specific genetic mutations. His work involves detailed pathological analysis and the identification of molecular markers relevant to cancer diagnosis and characterization.

Research topics

• Biology
• Cancer research
• Medicine
• Pathology
• Immunology

Selected publications

• Machine Learning Models Reveal New Risk Factors for Sub-/Supra-Therapeutic Concentrations of Sirolimus in Children with Vascular Anomalies

  Drug Design Development and Therapy · 2026-01-01

  articleOpen access

  Introduction: Sirolimus, also known as rapamycin, is an mTOR receptor inhibitor that suppresses cell proliferation and angiogenesis, demonstrating efficacy against multiple types of vascular anomalies. However, sub-therapeutic concentrations (below effective levels) and supra-therapeutic concentrations (leading to adverse reactions) of sirolimus may both negatively impact patient treatment outcomes. This study aimed to establish optimal models to predict the risk of sirolimus exposure using machine learning, ensure that sirolimus blood concentrations remain within the therapeutic range, and thus enhance the efficacy and safety of sirolimus therapy for children with vascular anomalies. Methods: We retrospectively analyzed 134 sirolimus therapeutic drug monitoring (TDM) measurements from 49 patients. Data were randomly split into training (80%) and testing (20%) sets, with an additional temporal cohort for external validation. Six machine learning models were developed to predict sub-therapeutic and supra-therapeutic risks, and evaluated primarily by the area under the receiver operating characteristic curve (AUROC) and Brier score. The optimal model was interpreted using SHapley Additive exPlanations (SHAP) analysis. Results: The sub-therapeutic risk model included body mass index (BMI), white blood cells (WBC), mean corpuscular hemoglobin (MCH), triglycerides (TG), and total bilirubin (TBIL); while the supra-therapeutic model comprised height, platelet count (PLT), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). The multilayer perceptron (MLP) and extreme gradient boosting (XGB) models showed optimal performance for sub-therapeutic (AUROC = 0.646, Brier = 0.190) and supra-therapeutic (AUROC = 0.825, Brier = 0.143) risk prediction, respectively, with consistent results in temporal validation (AUROC: 0.678, Brier = 0.190 and AUROC: 0.767, Brier = 0.190). Conclusion: This study is the first to use machine learning models to predict the risk of sub- or supra-therapeutic sirolimus concentrations in vascular anomalies children. By enabling personalized exposure risk prediction, the dosing accuracy of sirolimus for the treatment of children with vascular anomalies can be optimized, thereby enhancing effectiveness and safety.

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• Machine Learning-Enhanced Cerebrospinal Fluid N-Glycome for the Diagnosis and Prognosis of Primary Central Nervous System Lymphoma

  Journal of Proteome Research · 2025-04-22 · 2 citations

  article

  The diagnosis and prognosis of Primary Central Nervous System Lymphoma (PCNSL) present significant challenges. In this study, the potential use of machine learning algorithms in diagnosing and predicting the prognosis for PCNSL based on cerebrospinal fluid (CSF) N-glycomics was investigated. First, CSF samples obtained from a cohort of 60 PCNSL patients and 30 controls were analyzed by hydrophilic interaction-based ultra performance liquid chromatography (HILIC-UPLC)-fluorescence mass spectrometry. Subsequently, nine machine learning models were established to diagnose PCNSL based on the changes of CSF N-glycome, with the Random Forest algorithm proving to be the most effective, achieving an accuracy of 100% in the training set and 89.3% in the test set. Moreover, a COX proportional-hazard model and a nomogram incorporating CSF N-glycome (GP6 and GP27) along with clinical data (age) were crafted. This nomogram's discrimination capacity was considered satisfactory, as evidenced by a C-index of 0.804 (95% CI: 0.68, 0.927). The study reveals that machine learning models based on CSF N-glycome offer a valuable approach for diagnosing and prognosticating PCNSL, demonstrating high accuracy and sensitivity in both classification and survival analysis. These findings may offer new insights into the molecular mechanisms underlying PCNSL and contribute to the advancement of personalized medicine for patients with this disease.

  PublisherDOI

• Transgenerational Cold Acclimation and Contribution of Gut Bacteria in Spodoptera frugiperda

  Insects · 2025-10-16 · 1 citations

  articleOpen accessCorresponding

  The study of cold stress and adaptability can provide a theoretical basis for predicting and controlling pests. Temperature shapes gut microbiota composition, and gut microbiota may affect insect temperature tolerance. However, the underlying mechanisms and bacteria species involved in insect temperature tolerance through gut microbiota are still poorly known. In this study, using a multigenerational cold-acclimation design and 16S rDNA sequencing, we investigated the possible pattern of cold acclimation and the contribution of gut bacteria in Spodoptera frugiperda. Results show that during cold acclimation, larval mortality decreased and pupation rate increased with the increase of treating generations, exhibiting some sort of cold adaptation. Cold tolerance tests showed that cold-acclimated adults exhibited significantly higher survival rates under extreme cold stress than those of controls. Cold acclimation also leads to the cost of reproductive fitness, indicating some trade-offs between survival and reproduction. Antibiotic treatment significantly decreased fitness and cold tolerance not only in the un-acclimated lines but also in cold-acclimated lines. Biodiversity studies through 16S RNA sequencing suggested that antibiotic ingestion disrupted the homeostasis of gut microbes. Differential analysis at the genus and species levels further showed that there were nine genera and eight species that had remarkably higher abundance in cold-acclimated lines compared with controls. References-based functional annotation revealed that most of these bacteria may play essential roles in the cold adaptation of hosts. These results provide valuable insights into the contribution of microbiota to insect fitness and will be valuable for guiding the future development of sustainable pest management approaches.

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• Thoracic paravertebral osteosarcoma induced by radiotherapy for esophageal cancer: A case report

  Oncology Letters · 2025-08-18

  articleOpen accessSenior author

  With the wide application of radiation therapy for malignant tumors and the continuous improvement of comprehensive treatment effect, the survival period of patients has been prolonged, while the incidence of radiation-induced osteosarcoma (RIOS) has gradually increased. Compared with primary osteosarcoma, RIOS has a higher degree of malignancy and poorer prognosis, severely impacting patient survival. Currently, there are relatively few case reports on RIOS and the understanding of its imaging characteristics remains incomplete. A patient with esophageal cancer who was found to have thoracic paravertebral masses six years after receiving radiotherapy was encountered at Zhuji People's Hospital (Zhuji, China). Computed tomography (CT), magnetic resonance imaging and positron emission tomography/CT all indicated the presence of the malignant tumors. Subsequently, the patient was hospitalized for CT-guided puncture biopsy of thoracic paravertebral masses. Through multidisciplinary discussions in the departments of Medical Oncology, Orthopedics, Radiology and Pathology, a consensus was finally reached on RIOS. In conclusion, RIOS is a severe and relatively rare complication of radiotherapy with a poor prognosis. In its early stage, it is easily confused with bone changes after radiotherapy and appearance deformities after surgery. Neoplastic bone is the primary imaging feature of RIOS of esophageal cancer. By combining the patient's radiotherapy history and laboratory examinations, the diagnostic accuracy for this disease could be improved.

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• Estrogen Receptor (ER) and Progesterone Receptor (PR) Immunohistochemistry is Sensitive and Specific for Differentiating Retroperitoneal Leiomyosarcomas With Symplastic-like Features From Their Uterine Mimics

  International Journal of Gynecological Pathology · 2025-09-03 · 1 citations

  article1st authorCorresponding

  Previous studies have evaluated the utility of estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry (IHC) in differentiating uterine versus extrauterine leiomyosarcomas (LMS). At best, these studies have shown only modest sensitivity and specificity for these markers in this context. In our own practice, we have noticed that retroperitoneal LMS, such as those arising in the wall of the inferior vena cava, frequently exhibit a remarkable resemblance not to uterine LMS, but rather to uterine leiomyomas (LM) with bizarre nuclei, formerly known as symplastic LM. This includes areas with bland nuclear cytology, punctuated by the presence of cells with large bizarre nuclei but a paradoxically low mitotic index. We refer to these areas in retroperitoneal LMS as "symplastic-like." It has been our experience that these "symplastic-like" areas are frequently the predominant or exclusive component in small core biopsies of retroperitoneal LMS, even when the resection of these tumors reveals the presence of more conventional high-grade LMS morphology. In female patients, symplastic-like morphology in a smooth muscle tumor at an intra-abdominal site raises the possibility of iatrogenic dissemination of a uterine LM with bizarre nuclei from a prior myomectomy or morcellation procedure. We hypothesized that negative staining for ER and PR by IHC could effectively exclude a uterine origin, given the high sensitivity of these markers for all variants of uterine LM. After successfully using ER and PR IHC in our clinical practice on a few index cases, we decided to study a larger cohort of carefully selected cases to systematically determine the sensitivity and specificity of these markers in this very specific context. Confining our search to include only female patients, we identified 8 cases of retroperitoneal LMS that had been confirmed radiologically, intraoperatively and/or histologically to originate from a retroperitoneal source and 6 cases of uterine-based LM with bizarre nuclei, all diagnosed at our institution over an 8-year period. We tested only whole slides for ER and PR IHC. ER and PR were both completely negative in all 8 cases of retroperitoneal LMS and were both strongly expressed in all 6 cases of LM with bizarre nuclei. In conclusion, despite conflicting data in the literature regarding the utility of ER and PR in distinguishing uterine versus extrauterine smooth muscle tumors, we endorse the use of these markers for the specific distinction of retroperitoneal LMS with symplastic-like features from disseminated uterine LM with bizarre nuclei in female patients.

  PublisherDOI

• Multigenerational Heat Selection Enhancing Thermal Acclimation and Transcriptional Response of Hsps to Heat Stress in Spodoptera frugiperda Male Adults

  Insects · 2025-08-18 · 1 citations

  articleOpen accessSenior authorCorresponding

  . Results show that heat selection significantly shortened the larval and pupal developmental duration, which was maintained in the four tested generations. Significant costs to reproduction were found in the first two generations, but they recovered in the following generations. Heat-selected adults exhibited significantly higher survival rates under extremely high temperatures, and the survival rate increased with subsequent generations. Transcriptomic analysis between heat-selected and non-selected male adults from the first generation showed that heat stress did not induce the upregulation of any heat shock protein (Hsp) genes; in the fourth generation, however, heat stress resulted in the upregulation of a great number of Hsps, indicating a positive correlation between Hsp expression and heat tolerance. Further analysis also found differential expression in other genes associated with heat resistance, such as cuticle-, antioxidant-, and detoxification-related genes. Moreover, quite a number of stress response GO terms were enriched, such as response to heat and other abiotic stimuli. GO enrichment also showed that DEGs were enriched to many more terms related to metabolism. KEGG enrichment revealed that relatively more disease-, metabolism-, and immunity-associated pathways were enriched. The number of disease pathways increased with the selection temperature in the first generation, whereas it decreased with subsequent generations. This study offers new information for the understanding of the thermal acclimation process and mechanism of moth species, and facilitates the prediction and management of this major pest.

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• Longitudinal profiling of cerebrospinal fluid N-glycome dynamics in glioblastoma patients treated with apatinib

  Journal of Pharmaceutical and Biomedical Analysis · 2025-09-27 · 1 citations

  article
  PublisherDOI

• HPV-associated Endocervical Adenocarcinoma In Situ (AIS) With an ER+/Vimentin+/CEA− immunophenotype Mimicking Tubo-endometrioid Metaplasia

  International Journal of Gynecological Pathology · 2025-08-05

  article1st author

  HPV-associated endocervical adenocarcinoma in situ (AIS) is typically ER-, vimentin-, and CEA+. By contrast, tubo-endometrioid metaplasia (TEM), a well-known mimicker of AIS, is typically ER+, vimentin+, and CEA-. Both AIS and TEM express p16, with block-positive expression in AIS and predominantly patchy expression in TEM; however, TEM may also exhibit p16 expression that is extensive enough that it borders on block-like expression. Here we share 2 cases of endocervical AIS that showed an endometrioid immunophenotype (ER+, vimentin+, and CEA-). The AIS in these cases also had a second population of pale p40- epithelioid cells resembling the ciliated cells of TEM; no true cilia were seen. High-risk human papillomavirus (HPV) in situ hybridization (HR-HPV ISH) testing was positive in both cases of AIS, establishing their HPV association. Despite the lack of true cilia, the morphology and immunophenotype of the AIS in these cases resulted in a very TEM-like picture. Given the aforementioned propensity of TEM to show a high degree of p16 expression, we share these cases as a reminder that an endometrioid-like immunophenotype by ER, CEA, and vimentin IHC does not unequivocally establish a benign diagnosis.

  PublisherDOI

• A Case of CDKN2C/CIC Null Epithelioid Leiomyosarcoma With a Low-grade Component Indistinguishable From Leiomyoma

  International Journal of Gynecological Pathology · 2025-05-08 · 1 citations

  article

  Numerous emerging molecularly defined subtypes of uterine leiomyosarcoma (LMS) have been described in recent years. Here we report our experience with a challenging case of the recently described CDKN2C/CIC null subtype of LMS - a LMS subtype that is frequently epithelioid in appearance, is wild-type for both TP53 and RB1 and may exhibit low-grade histology that falls short of LMS. The 48-year-old patient was initially diagnosed with an epithelioid leiomyoma with a component of intravenous leiomyomatosis. Recurrence occurred 5 years later with an extensive disease burden in the abdomen and pelvis. Upon review, the lesion in the hysterectomy specimen and the recurrent tumor had similar morphology. This included (1) focal epithelioid morphology meeting current diagnostic criteria for epithelioid LMS and (2) other areas with morphology indistinguishable from leiomyoma (LM), including conventional spindle cell LM, cellular LM, and LM with bizarre nuclei. Targeted next-generation molecular analysis performed on both the original tumor in the hysterectomy specimen and the tumor from the recurrence showed the same CDKN2C/CIC null profile. This case highlights the striking intratumoral heterogeneity that is possible in CDKN2C/CIC null LMS, including areas morphologically indistinguishable from LM. Clinicopathological findings in this case, including features that may assist in recognizing this challenging LMS subtype, are discussed. We underscore the importance of early diagnosis, which can facilitate appropriate adjuvant and/or maintenance therapy that may decrease the morbidity associated with extensive debulking surgery.

  PublisherDOI

• Early recurrence and extensive retroperitoneal metastasis after surgery for high‑grade mucinous tubular and spindle cell carcinoma: A case report and literature review

  Oncology Letters · 2024-07-31 · 1 citations

  articleOpen access

  Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cancer. The present report details the treatment experience of a case of MTSCC, where the patient underwent a right-side laparoscopic nephrectomy in October 2020 at Zhuji People's Hospital (Zhuji, China). A total of 3 months post-operation, multiple metastases were discovered in the right renal area and retroperitoneum, with rapid disease progression observed in the subsequent 2 months. Treatment with tislelizumab combined with pazopanib was ineffective, and the patient subsequently died. Although MTSCC is generally considered a low-grade 'indolent' tumor, with most patients achieving long-term survival post-surgery, a minority of cases, especially those of a higher grade, may experience postoperative recurrence and metastasis. Due to the rarity of metastatic MTSCC, most studies are based on small sample sizes or case reports, and there is a lack of standardized systemic treatment and follow-up strategies for metastatic MTSCC. The present paper summarizes and analyzes the clinical features, treatment methods and prognosis of metastatic MTSCC cases reported in the literature, aiming to provide assistance for the treatment and follow-up management of metastatic MTSCC. Even in cases of distant metastasis, aggressive surgical treatment, metastasectomy combined with molecular targeted or immunotherapy, may still be recommended.

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Frequent coauthors

• Paul Weisman

  University of Wisconsin–Madison

  33 shared

• Kay J. Park

  18 shared

• William M. Rehrauer

  University of Wisconsin–Madison

  11 shared

• Daniel R. Matson

  University of Wisconsin–Madison

  10 shared

• Vanessa L. Horner

  University of Wisconsin–Madison

  9 shared

• Molly A. Accola

  University of Wisconsin–Madison

  9 shared

• Leah Frater-Rubsam

  9 shared

• Les Henderson

  University of Wisconsin–Madison

  9 shared