The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a “don't eat me” signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal3) expression correlated with CD47 expression, and coexpression of Gal3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal3–deficient tumor cells into either wild-type and Lgals3−/− mice led to a reduction in M2 macrophages and increased T-cell responses compared with Gal3 wild-type tumor cells, indicating that tumor cell–derived Gal3 plays a more important role in GAC progression and phagocytosis than host-derived Gal3. Dual blockade of Gal3 and CD47 collaboratively suppressed tumor growth, increased phagocytosis, repolarized macrophages, and boosted T-cell immune responses. These data uncovered that Gal3 functions together with CD47 to suppress phagocytosis and orchestrate immunosuppression in GAC with PC, which supports exploring a novel combination therapy targeting Gal3 and CD47. Significance: Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma.

Zinc-finger protein-326 (ZNF326) was initially found in the NIH3T3 cell line to regulate cell growth, however, the expression and underlying role of ZNF326 in human tumours, especially in glioma, is not fully understood. Immunohistochemistry was applied to detect the expression of ZNF326 in glioma tissues, and statistical analysis was used to analyse the relationship between ZNF326 expression and clinicopathological factors. The effect of ZNF326 on glioma cells proliferation and invasion was conducted by functional experiments both in vivo and in vitro. Chromatin immunoprecipitation and dual-luciferase assays were performed to demonstrate that histone deacetylase enzyme-7 (HDAC7) is the target gene of ZNF326. Immunoblotting, real-time PCR, GST-pulldown and co-immunoprecipitation assays were used to clarify the underlying role of ZNF326 on Wnt pathway activation. High nuclear expression of ZNF326 was observed in glioma cell lines and tissues, and closely related with advanced tumour grade in the patients. Moreover, ectopic ZNF326 expression promoted the proliferation and invasiveness of glioma cells. Mechanistically, ZNF326 could activate HDAC7 transcription by binding to a specific promoter region via its transcriptional activation domain and zinc-finger structures. The interaction of the up-regulated HDAC7 with β-catenin led to a decrease in β-catenin acetylation level at Lys-49, followed by a decrease in β-catenin phosphorylation level at Ser-45. These changes in β-catenin posttranscriptional modification levels promoted its redistribution and import into the nucleus. Additionally, ZNF326 directly associated with β-catenin in the nucleus, and enhanced the binding of β-catenin to TCF-4, serving as a co-activator in stimulating Wnt pathway. Our findings elucidated ZNF326 promotes the malignant phenotype of human glioma via ZNF326-HDAC7-β-catenin signalling. This study reveals the vital role and mechanism of ZNF326 in the malignant progression of glioma, and provides the reference for finding biomarkers and therapeutic targets for glioma.

This study evaluated the diagnostic value of clinicopathological features and immunohistochemical markers for distinguishing lipomas from atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPS). An integrated diagnostic model for ALT/WDLPS was developed to guide diagnosis, treatment planning, and prognosis. This retrospective analysis included 216 patients with lipomatous tumors diagnosed between February 2018 and December 2024, including lipomas (n = 149), spindle cell lipomas (n = 3), ALTs/WDLPs (n = 62), and WDLPS with a low-grade de-differentiated component (n = 2). Immunohistochemical data for MDM2, CDK4, and p16 were available for 131 patients. MDM2 amplification was significantly more frequent in patients ≥ 55 years and in tumors of the lower limbs (the thigh) and retroperitoneum (p = 0.000). Larger tumor size and multiplicity were also associated with MDM2 amplification (p < 0.05). Immunohistochemistry sensitivities for ALT/WDLPS vs. lipomas: 65% (MDM2), 100% (CDK4), and 80.4% (p16); combined, the specificity was 100% and sensitivity 85.6%. The diagnostic model achieved 93.3% sensitivity and 72.2% specificity. Scores < 0.219 indicated a higher likelihood of lipoma, while scores > 0.652 indicated a higher likelihood of liposarcoma. Age ≥ 55 years, lower extremity/retroperitoneal location, tumor diameter ≥ 9.9 cm, and positive markers were independent risk factors. This model provides an effective tool for ALT/WDLPS identification.

Introduction: This retrospective study aimed to investigate the correlation between TP53 identified via next-generation sequencing (NGS) and p53 expression in colorectal adenocarcinoma (CRC), as assessed by immunohistochemistry (IHC). Additionally, we characterized p53 IHC staining patterns and sought to determine the optimal threshold for p53 expression as a surrogate for TP53 mutation status. Methods: In this retrospective cohort analysis, we included 294 archived surgically resected CRC specimens from patients who did not receive preoperative chemotherapy were analyzed. All data were collected from pathology database and electronic medical records. TP53 mutations were identified using NGS, and p53 expression was evaluated by IHC. The correlation between mutation status and IHC staining patterns was assessed, and sensitivity and specificity were calculated. Results: The TP53 mutation rate was 78.2%, comprising missense (68.4%), nonsense (12.4%), frameshift (11.0%), and splice-site (8.3%) mutations. Missense mutations were associated with nuclear p53 staining, while frameshift mutations mostly showed loss of expression. Nonsense and splice-site mutations exhibited diverse patterns, including loss of expression, nuclear staining with/without cytoplasmic staining, or cytoplasmic staining alone. Among cases with loss of p53 expression, the TP53 mutation rate was 88.9%. When the proportion of strong p53-positive cells exceeded 55%, the missense mutation-positivity rate increased significantly (P < 0.05). The sensitivity and specificity of p53 IHC in predicting TP53 mutations were 92.3% and 94.8%, respectively. Conclusions: CRC predominantly exhibited missense TP53 mutations. p53 IHC revealed diverse expression patterns, including overexpression, complete loss, cytoplasmic staining, and normal-type patterns. Strong p53 expression (>55%) correlated closely with TP53 missense mutations, supporting IHC as a reliable surrogate. However, cases showing loss of p53 expression should undergo gene sequencing to confirm mutation status.

The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a “don't eat me” signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal3) expression correlated with CD47 expression, and coexpression of Gal3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal3–deficient tumor cells into either wild-type and Lgals3−/− mice led to a reduction in M2 macrophages and increased T-cell responses compared with Gal3 wild-type tumor cells, indicating that tumor cell–derived Gal3 plays a more important role in GAC progression and phagocytosis than host-derived Gal3. Dual blockade of Gal3 and CD47 collaboratively suppressed tumor growth, increased phagocytosis, repolarized macrophages, and boosted T-cell immune responses. These data uncovered that Gal3 functions together with CD47 to suppress phagocytosis and orchestrate immunosuppression in GAC with PC, which supports exploring a novel combination therapy targeting Gal3 and CD47.Significance:Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma.

The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a “don't eat me” signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal3) expression correlated with CD47 expression, and coexpression of Gal3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal3–deficient tumor cells into either wild-type and Lgals3−/− mice led to a reduction in M2 macrophages and increased T-cell responses compared with Gal3 wild-type tumor cells, indicating that tumor cell–derived Gal3 plays a more important role in GAC progression and phagocytosis than host-derived Gal3. Dual blockade of Gal3 and CD47 collaboratively suppressed tumor growth, increased phagocytosis, repolarized macrophages, and boosted T-cell immune responses. These data uncovered that Gal3 functions together with CD47 to suppress phagocytosis and orchestrate immunosuppression in GAC with PC, which supports exploring a novel combination therapy targeting Gal3 and CD47.Significance:Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma.