MZB1 (Marginal Zone B and B1 Cell-Specific Protein), an endoplasmic reticulum-resident protein, has recently garnered significant attention for its role in immune regulation. As a critical modulator within various immune cells, MZB1 influences key processes such as cell differentiation, antibody production, and immune microenvironment dynamics. Despite advances in understanding, the precise mechanisms by which MZB1 contributes to immune homeostasis and dysregulation in pathological conditions remain incompletely defined. Emerging evidence highlights its involvement in tumor biology, inflammatory responses, and autoimmune diseases, positioning MZB1 as a potential therapeutic target. This review aims to synthesize current research findings on MZB1's functions across different immune cell types, elucidate its interactions with other immune regulatory factors, and explore its impact on the tumor microenvironment and immune-mediated disorders.

[This corrects the article DOI: 10.3389/fimmu.2025.1705852.].

Lung cancer ranks as the leading cause of cancer-related mortality worldwide, characterised by complex molecular mechanisms and high therapeutic resistance. Ubiquitin-specific proteases, as core members of the deubiquitinating enzyme family, extensively participate in the initiation, progression, metastasis, and treatment resistance of lung cancer by regulating the stability of key proteins. Recent studies indicate that multiple Ubiquitin-Specific Proteases (USP) family members play pivotal roles in lung cancer: Ubiquitin-Specific Peptidase 7 (USP7) promotes proliferation and osimertinib resistance in non-small cell lung cancer by stabilising proteins such as ERβ, c-Abl, and KRAS; Ubiquitin-Specific Peptidase 9, X-linked (USP9X) mediates radiotherapy resistance by regulating KDM4C and REV1; USP10 influences cellular metabolism and chemotherapy sensitivity via PTEN/AKT/mTOR and HDAC6 pathways; Ubiquitin-Specific Peptidase 14 (USP14) enhances tumour migration by regulating β-catenin and Acf7 stability; Ubiquitin-Specific Peptidase 22 (USP22) amplifies tumour stem cell properties and suppresses ferroptosis via EGFR and BMI1 signalling; Ubiquitin-Specific Peptidase 35 (USP35) and Ubiquitin-Specific Peptidase 38 (USP38) respectively modulate apoptosis resistance and proliferation through BIRC3 and KLF5; while Ubiquitin-Specific Peptidase 39 (USP39) influences mitochondrial metabolism via PDHA, thereby promoting tumour growth. This paper systematically reviews the mechanisms of action of the aforementioned USPs in multiple key signalling pathways, including KRAS, TGF-β/SMAD, ferroptosis, and DNA damage repair. It further explores the potential value of small-molecule inhibitors targeting USPs (such as P5091, IU1, and gentiopicroside) in reversing drug resistance, inducing apoptosis, and enhancing immunotherapy. Nevertheless, current research remains subject to certain limitations, including insufficient systematic and synergistic understanding of USP family members' functions, poor inhibitor selectivity and preclinical toxicity concerns, as well as unresolved functional heterogeneity across different molecular subtypes of lung cancer. This paper reviews the molecular mechanisms and targeting strategies of USPs in lung cancer based on a systematic literature search of PubMed and Web of Science databases. It further explores their potential applications in precision lung cancer therapy, providing theoretical foundations and directional guidance for future research.

The diagnosis of prostate cancer and prostatitis becomes challenging when using biparametric Magnetic Resonance (MR) images. This research investigates deep learning models to assess their capability for improving diagnostic accuracy and assisting radiologists.

This retrospective study analyzed 153 patients who received histopathological diagnoses of prostate cancer or prostatitis between January 2017 and December 2023. Patients were categorized according to PI-RADS scores, and both T2A and ADC-DWI (Apparent Diffusion Coefficient-Diffusion-Weighted Imaging) sequences were examined. Expert radiologists labeled the images prior to lesion detection with the Faster R-CNN (Faster Region-based Convolutional Neural Network) model. Nine different classification models were trained using normal and augmented datasets to evaluate their performance. Model reliability was further assessed through cross-validation and statistical significance testing.

The Faster R-CNN model achieved 96% accuracy (95% CI: 93.2-98.8%) for P5 and 99% accuracy (95% CI: 96.7-100%) for prostatitis in T2A sequences, and 90% accuracy (95% CI: 85.4-94.6%) for P5 and 97% accuracy (95% CI: 93.8-100%) for prostatitis in ADC-DWI sequences. However, the model failed to effectively detect P4 lesions (0% sensitivity in T2A and 30% in ADC-DWI). The model demonstrated comparable performance to expert radiologists, with no significant difference in overall P5 detection (p > 0.05), and Cohen's kappa indicated substantial agreement (κ = 0.86). The classification models achieved up to 97% accuracy with InceptionV3 in T2A sequences and up to 99% accuracy with DenseNet201 in ADC-DWI sequences. To further evaluate discriminative performance, AUROC values were calculated for all classification models. In T2A sequences, AUROC scores were DenseNet201 (0.98), EfficientNetV2L (0.99), InceptionV3 (0.99), MobileNetV2 (0.92), NASNetLarge (0.83), ResNet50 (0.76), VGG16 (0.98), VGG19 (0.97), and Xception (0.96). In ADC-DWI sequences, AUROC values were DenseNet201 (0.99), EfficientNetV2L (0.96), InceptionV3 (0.99), MobileNetV2 (0.82), NASNetLarge (0.90), ResNet50 (0.64), VGG16 (0.96), VGG19 (0.86), and Xception (0.97), reinforcing the superior discriminative ability of DenseNet201 and InceptionV3 across modalities.

The deep learning models demonstrated promising diagnostic capabilities, comparable to radiologists, in distinguishing prostatitis and P5 prostate cancer lesions. Overall, the findings suggest that AI-based diagnostic tools hold potential as clinical decision support systems.

Diarrhea usually appears early following autologous hematopoietic stem cell transplantation (ASCT) due to toxic mucosal damage and neutropenia. Infectious agents also cause diarrhea in the post-transplantation period, with Clostridium difficile (C. difficile) being most common. In contrast, cytomegalovirus (CMV) enterocolitis is extremely rare after ASCT. We report a case of a 55-year-old male who underwent ASCT for non-Hodgkin lymphoma that was complicated by severe persistent diarrhea resulting in significant hypovolemia and electrolyte imbalance. Prior to transplantation, the patient received rituximab in combination with chemotherapy (R-CHOP/R-DHAP) followed by a bendamustine-based conditioning regimen (BeEAM). After treatment with oral metronidazole, vancomycin and fidaxomicin, diarrhea persisted despite undetectable C. difficile toxin, with elevation of hepatic enzymes. Eventually, CMV infection was diagnosed by real-time polymerase chain reaction and treated with ganciclovir and valganciclovir. Due to hypogammaglobulinemia following previous rituximab treatment, CMV immunoglobulins were also administered. The patient's condition gradually improved with CMV DNA being undetectable in serum. This case shows that diarrhea may be caused by concurrent infection with C. difficile and CMV after ASCT. Bendamustine-induced colitis and prior rituximab treatment may have been additional risk factors in this patient. Therefore, more comprehensive workup of diarrhea is needed in ASCT recipients treated with these agents.

Ameloblastic carcinoma is a rare malignant epithelial tumor, mostly affecting the mandible. Maxillary ameloblastic carcinoma is even more uncommon and its clear cell variant has been exceedingly rarely described. Because clear cell lesions of jaw bones are both rare and diagnostically challenging, the incidence of the tumor, as well as the criteria for classification are not precisely defined. Differential diagnosis includes a variety of benign or malignant tumors of odontogenic and salivary gland origin, as well as metastatic tumors. Diagnostic dilemma extends to therapeutic approach. Treatment modalities are still debated. The present case report discusses the clinical and histologic differential diagnosis of clear cell variant of an aggressive maxillary ameloblastic carcinoma which was successfully treated with preoperative radiation therapy, followed by surgical excision of the residual lesion and reconstruction of the maxilla.

MECOM (the MDS1 and EVI1 complex locus) rearrangements have been identified as an independent high-risk factor in acute myeloid leukemia (AML). The diversity of MECOM rearrangement partner genes significantly influences disease mechanisms and prognosis. The majority of atypical MECOM rearrangements result in EVI1 overexpression through translocation into super-enhancer-containing regions. This report describes a rare, recurrent MBNL1::MECOM rearrangement identified in a myelodysplastic neoplasm (MDS) patient with a concurrent SF3B1 mutation. Although conventional cytogenetics showed a normal karyotype, the rearrangement was confirmed by next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH). Concurrently, the patient exhibited high EVI1 expression, consistent with the common mechanism observed in atypical MECOM rearrangements. Given the well-documented association between SF3B1 mutations and MECOM rearrangements, analysis of MECOM expression and RNA sequencing (RNA-seq) is crucial for SF3B1-mutated patients, even in the absence of elevated blast counts. Furthermore, this case underscores the need for further research into the synergistic biological role of spliceosome mutations and MECOM rearrangements in driving leukemia.

Thyroid transcription factor-1 (TTF-1) is a well-established immunohistochemical marker for tumors of lung and thyroid origin. Metastatic adenocarcinomas are often tested for TTF-1 expression to identify their primary site. Herein, we report a rare case of TTF-1-positive primary gastric adenocarcinoma that was initially misdiagnosed and treated as postoperative gastric metastasis from primary lung cancer.

A 58-year-old man underwent thoracoscopic right upper lobectomy with systemic lymph node dissection for lung cancer of the right upper lobe. The pathological diagnosis was invasive adenocarcinoma (pT2bN0M0, Stage IIA). He received 3 courses of postoperative adjuvant platinum doublet chemotherapy. One year and 2 months after surgery, he was diagnosed with gastric and adrenal tumors. Immunohistochemical analysis of the gastric lesion demonstrated TTF-1 positivity, leading to the diagnosis of gastric and adrenal metastatic recurrence of lung cancer. The patient received triple therapy with carboplatin, pemetrexed, and pembrolizumab, followed by maintenance therapy with pemetrexed and pembrolizumab. During treatment, the adrenal metastasis achieved a complete response; however, the gastric lesion showed gradual progression on endoscopic follow-up. As primary gastric cancer could not be ruled out, the patient underwent robot-assisted distal gastrectomy with D2 lymph node dissection and Billroth I reconstruction, 3 years and 4 months following lung resection. Immunohistochemical staining of the gastric tumor revealed adenocarcinoma that was positive for TTF-1 and caudal-related homeodomain protein 2 (CDX2) and negative for napsin A. In contrast, lung cancer tissue was weakly positive for TTF-1 and negative for napsin A and CDX2. Based on the immunohistochemical staining and histological findings, the final diagnosis was primary gastric adenocarcinoma. The postoperative course was uneventful, and maintenance chemotherapy with pemetrexed and pembrolizumab was resumed. Four years and 10 months after cancer surgery, the patient remains in complete response.

This case highlights the diagnostic challenge posed by TTF-1-positive gastric tumors, which may be mistaken for metastatic lesions from lung cancer. As TTF-1 expression is not entirely specific to tissues of lung or thyroid origin, diagnosis should be based on a comprehensive evaluation of morphological and immunohistochemical findings, together with clinical information, including treatment response and disease course.

Papillary tumor of the pineal region (PTPR) is a rare central nervous system neoplasm with an unpredictable clinical course. Gross total resection, the preferred treatment, is often unachievable due to the tumor's deep-seated location, necessitating alternative therapies. We report the case of a 24-year-old male with recurrent grade 3 PTPR. Initial subtotal resection followed by adjuvant volumetric modulated arc therapy (50.4 Gy in 28 fractions) failed to control tumor progression. After a second subtotal resection for recurrence, the patient underwent fractionated stereotactic radiotherapy (fSRT) using Gamma Knife Icon, delivering a total dose of 28 Gy in eight fractions. One year post-fSRT, significant tumor shrinkage was observed, and the patient maintained clinical stability. This case highlights fSRT's potential as an effective salvage treatment for recurrent PTPR, particularly in anatomically challenging regions where gross total resection is not feasible. To our knowledge, this is the first report detailing the successful use of fractionated Gamma Knife radiosurgery for a large, recurrent primary PTPR refractory to previous multimodal treatment, suggesting a valuable therapeutic option for this challenging condition.

The emergence of the EGFR C797S mutation poses a significant challenge in the treatment of non-small cell lung cancer due to resistance to third-generation EGFR-tyrosine kinase inhibitors. This study introduces a novel and highly selective EGFR PROTAC, HBE-843, designed to degrade mutant EGFR while sparing wild-type EGFR. Our degrader not only effectively degrades the L858R but also shows promising activity against exon 19 deletion, T790M, and C797S, where it demonstrated low nanomolar GI₅₀ (26-103 nM) across all these EGFR mutant-harboring cell lines while sparing the wild-type. HBE-843 effectively reduced EGFR protein levels in mutant cells in a dose-dependent manner, with a DC₅₀ in the low nanomolar range (1.9-18 nM) and a D_max above 90%. Mechanistic studies showed that HBE-843 mediates EGFR degradation through the CRBN-associated proteasome pathway, preventing the activation of the ERK downstream signal and hindering cell growth. In vivo studies demonstrated a 112% tumor growth inhibition in L858R-induced cancers. These findings suggest that HBE-843 holds promise as a lead compound for developing new drugs to overcome C797S mutant-mediated resistance in clinical settings.