[This corrects the article DOI: 10.21037/tcr-24-587.].
Background: Breast cancer is a highly heterogeneous malignancy that poses a major health threat to women. Contemporary clinical management relies heavily on molecular subtyping, in which the Ki-67 proliferation index serves as a critical biomarker for assessing tumor aggressiveness and recurrence risk. However, conventional Ki-67 evaluation depends on invasive biopsy and immunohistochemical analysis, whose accuracy can be compromised by tumor heterogeneity-induced sampling errors and inter-observer variability. Therefore, this study aimed to develop and validate a preoperative nomogram that integrates multimodal ultrasound features with clinical parameters to enable non-invasive preoperative assessment of Ki-67 expression status in breast cancer.
Methods: We retrospectively enrolled 142 consecutive breast cancer patients from The Third Affiliated Hospital of Kunming Medical University's Breast Center (March 2022 to August 2024). Preoperative multimodal ultrasound parameters (including B-mode, Doppler, and shear-wave elastography) and clinical variables were systematically documented using standardized protocols. Variables demonstrating univariate associations (P<0.10) underwent forward stepwise multivariate regression using likelihood ratio criteria. Model performance was assessed through: (I) calibration curves with Hosmer-Lemeshow test; (II) discrimination via area under the curve (AUC); and (III) clinical utility by decision curve analysis. Internal validation employed bootstrap resampling (1,000 replicates) with optimism correction using Harrell's method.
Results: Univariate analysis identified six predictors associated with Ki-67 status (P<0.10): maximum lesion diameter, hyperechoic halo presence, Adler grade, Eratio, posterior echo reduction, and calcifications. Multivariate analysis confirmed four independent predictors of Ki-67 status (P<0.05): hyperechoic halo presence [adjusted odds ratio (aOR) =7.934; 95% confidence interval (CI): 2.604-24.173], posterior echo reduction (aOR =0.245; 95% CI: 0.099-0.601), calcifications (aOR =3.524; 95% CI: 1.466-8.472), and Adler grade (aOR =2.334; 95% CI: 1.222-4.456). The resulting nomogram demonstrated good discrimination (AUC =0.797; 95% CI: 0.722-0.872), with bootstrap-corrected AUC of 0.771 (95% CI: 0.673-0.879).
Conclusions: The validated nomogram provides clinically useful preoperative prediction of Ki-67 status (AUC =0.797; bootstrap-corrected 0.771), with hyperechoic halo presence, posterior echo reduction, calcifications, and high Adler grade as key predictors.
Background: Lower grade gliomas (LGGs) exhibit significant molecular and clinical heterogeneity, challenging accurate prognosis and treatment strategies based on current parameters. Alterations in fatty acid metabolism (FAM) have been implicated in tumor initiation, proliferation, and metastasis. This study investigates the role of FAM in LGGs to enhance patient management.
Methods: Gene expression data from The Cancer Genome Atlas (TCGA) database were analyzed to identify FAM-related genes with differential expression in LGGs. A prognostic model was constructed using Cox regression and least absolute shrinkage and selection operator regression. The model's predictive efficacy was validated using both TCGA test and Chinese Glioma Genome Atlas databases. Functional analyses included Gene Ontology, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration analysis. Drug sensitivity was assessed based on patient risk scores. Finally, we utilized the Human Protein Atlas (HPA) database to conduct a comparative analysis of protein expression patterns for the identified prognostic genes between LGG samples and normal cerebral cortex tissue.
Results: The prognostic model comprised four genes: carnitine palmitoyltransferase 2 (CPT2), glycerol-3-phosphate dehydrogenase 1 (GPD1), 17-beta hydroxysteroid dehydrogenase 10 (HSD17B10), and uroporphyrinogen synthase (UROS). LGG cases were stratified into high- and low-risk groups, with the high-risk group demonstrating markedly poorer survival rates (P<0.001). The high-risk group also exhibited increased expression of immune checkpoint-related genes, suggesting a potentially enhanced response to immunotherapy. Drug sensitivity analysis indicated that high-risk individuals might be more responsive to chemotherapy, particularly temozolomide and carmustine. The HPA database analysis showed high expression of CPT2, GPD1, and HSD17B10 proteins in LGGs, while UROS protein levels were low or undetectable.
Conclusions: This study underscores the prognostic role of the FAM-related risk model for LGGs. Assessing patient risk scores through this model could help tailor personalized treatments, providing valuable guidance for clinical decision-making.
Background: Esophageal carcinoma (ESCA) is a highly lethal malignancy with poor prognosis and limited treatment options. The identification of effective prognostic biomarkers and therapeutic targets remains an important goal in improving outcomes for patients with ESCA. While the involvement of programmed cell death (PCD) mechanisms in cancer remains underexplored, they are thought to influence some aspects of tumor biology. The purpose of this study was to construct a prognostic signature derived from PCD-related long non-coding RNAs (lncRNAs) in ESCA.
Methods: Transcriptome and clinical data from ESCA patients were sourced from The Cancer Genome Atlas (TCGA) database. Candidate lncRNAs associated with PCD and patient prognosis were identified and subjected to univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression to build a prognostic signature. The signature's predictive performance was validated internally. To explore possible mechanisms underlying risk stratification, we employed multiple approaches, including weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and assessment of immune cell infiltration patterns.
Results: Eight PCD-related lncRNAs (AC109347.1, BLACE, AP001527.2, AP001001.1, LINC00402, AC087289.5, FAM83C-AS1, and AL132655.2) were screened and incorporated into the prognostic signature. The signature appeared capable of distinguishing between high- and low-risk groups with distinct survival outcomes. Downregulation of immune-related pathways was observed in high-risk patients based on WGCNA and GSEA analyses. Immune cell infiltration and immune scoring metrics were comparatively lower in high-risk individuals. Based on drug response predictions, we identified potential agents that could be preferentially effective in high-risk ESCA patients.
Conclusions: In conclusion, the PCD-related lncRNAs signature constructed in this study may contribute to prognosis assessment in ESCA and offers preliminary indications of immune involvement worthy of further investigation.
Background: Immunotherapy has emerged as an effective treatment for many cancers. However, only a proportion of gastric cancer (GC) patients can benefit from immunotherapy. Thus, assessing different immune checkpoints, which regulate T-cell activation and function, is critical. This study aimed to explore the role of the six immune checkpoints, including B7-H3, B7-H4, PD-L1, PD-1, VISTA, and TIGIT, in GC.
Methods: The expression patterns of the six immune checkpoints in 478 GC patients were evaluated by immunohistochemistry. The relationships between immune checkpoints, clinicopathological features, and overall survival (OS) were analyzed.
Results: The positivity rates for B7-H3 in tumor cells (TCs) and stromal cells (SCs), B7-H4 in TCs, PD-L1 in TCs and SCs, PD-1 in immune cells (ICs), VISTA in ICs, and TIGIT in ICs were 36.2%, 63.2%, 2.3%, 16.7%, 25.1%, 59.0%, 37.4%, and 30.5%, respectively. Except for B7-H4, other immune markers were positively correlated with each other. An immune score (IS) based on the expression of four prognostic markers (B7-H3, PD-L1, VISTA, and TIGIT), was devised. Patients were classified as high-IS (40.8%) and low-IS (59.2%). The multivariate analysis showed IS to be an independent prognostic biomarker for OS (hazard ratio: 2.212, 95% confidence interval: 1.597-3.063, P<0.001).
Conclusions: This study identified different expression patterns of six immune checkpoints in GC, and IS based on the expression of four markers, could serve independently as a predictor of OS in GC, which might provide potential immune targets for GC patients.
Background: The underlying etiology of liver disease, such as metabolic dysfunction-associated steatotic liver diseases (MASLDs) or alcohol-related liver injury, significantly affects liver function and regenerative capacity. In hepatocellular carcinoma (HCC) patients undergoing hepatectomy, these background factors may influence postoperative outcomes and long-term survival. This study aimed to evaluate the impact of different etiologies of liver disease on survival outcomes following curative hepatectomy in patients with HCC.
Methods: We retrospectively analyzed patients with HCC who underwent curative hepatectomy at two academic institutions. Background liver disease was classified according to etiology, including viral liver disease (VLD), alcohol-related liver disease (ALD), MASLD, and others. Survival outcomes were evaluated and compared across etiological groups at two institutions from 1994 to 2023.
Results: Patients with VLD, ALD, and MASLD exhibited significantly elevated rates of advanced liver fibrosis (P<0.001), while vascular involvement was less frequent in MASLD cases. No significant differences in tumor stage, tumor markers, or postoperative complications were found among the etiologies. However, tumor recurrence was significantly more common in the VLD and ALD groups (P<0.001), and HCC-related deaths were most frequent in the VLD and other/unknown groups. MASLD patients presented the most favorable outcomes, with a 5-year recurrence-free survival (RFS) of 54% and a 10-year overall survival (OS) of 100%, significantly better than VLD (RFS 31%, OS 49%; P<0.01). Multivariate analysis revealed that VLD, vascular invasion, R1 margin, and poor liver function were independent predictors of recurrence and poor OS. Conversely, MASLD was not a significant risk factor for recurrence and was independently associated with better survival (P<0.05).
Conclusions: MASLD-related HCC represents a distinct clinical entity with relatively indolent tumor behavior and better-preserved liver function. Recognizing the prognostic implications of MASLD-related HCC is essential for optimizing surgical indications and developing etiology-specific treatment strategies.
Background: Compared with female breast cancer (FBC), male breast cancer (MBC) is often detected at the advanced stage and has a poorer prognosis. Due to the limited research data on MBC, its clinical diagnosis and treatment regimens are mainly based on FBC, although these regimens may not be appropriate for MBC patients. This study aimed to investigate the similarities and differences between MBC and FBC at the genetic level, in order to provide ideas and basis for the diagnosis and treatment of MBC.
Methods: In this cross-sectional study, we conducted high-throughput sequencing on formalin-fixed paraffin-embedded (FFPE) samples obtained from a cohort of 12 MBC and 14 FBC patients. Utilizing bioinformatics tools, we meticulously analyzed and compared the genomic profiles to elucidate the underlying genetic distinctions between MBC and FBC.
Results: In our study, MLL3 and GATA3 mutations were most prevalent in MBC while TP53, PIK3CA and MLL3 mutations dominated in FBC. Notably, certain genes exhibited shared point mutations and copy number variations (CNVs) across genders. The mutation prevalence of PIK3CA was significantly different between MBC and FBC. CDK12 and ERBB2 had the highest prevalence of CNV in FBC, contrasting with their absence in MBC. Both in MBC and FBC, MYC had the highest prevalence in CNV. Furthermore, FBC demonstrated a higher tumor mutational burden (TMB) than MBC. MBC private genes were involved in a variety of disease-related signaling pathways, with the ErbB and PI3K-Akt pathways being significantly enriched.
Conclusions: We concluded that MBC and FBC exhibit both genomic similarities and distinctions in our study. In the context of precision medicine, this study may provide new ideas and a basis for the diagnosis and treatment of MBC.
Background: Neuroblastoma (NB) is an embryonic cancer arising from neural crest cells. Long non-coding RNA (lncRNA) plays an important role in the development of tumors. Several studies have reported that LINC01296 and thyroid hormone receptor interacting protein 13 (TRIP13) acts as oncogenic regulators of cancer. However, their deep specific biological mechanisms in tumor metastasis are not known. Here, we aimed to elucidate whether LINC01296 or TRIP13 drives NB proliferation and progression, and to assess their potential as therapeutic targets.
Methods: In this study, we utilized the NB cell line SK-N-SH to investigate the roles of LINC01296 and TRIP13 by bacterial transformation and polymerase chain reaction (PCR) verification. Cells were infected with lentivirus, and fluorescence expression was monitored. Total RNA was extracted for reverse transcription quantitative PCR (RT-qPCR). Cell proliferation was assessed by using Cell Counting Kit-8 (CCK-8) assay. Migration was evaluated using wound-healing assays, and invasion was tested via Transwell with Matrigel-coated chambers. Apoptosis was analyzed by flow cytometry. For in vivo studies, non-obese diabetic/severe combined immunodeficiency (NOD/scid) mice were subcutaneously injected with 1×107 cells/mL suspended in Matrigel. Tumor growth was measured every 2 days for 23 days; tissues were harvested for paraffin sections or stored at -80 ℃. Immunohistochemistry (IHC) involved antigen retrieval, blocking with 5% normal serum, primary antibody incubation, and counterstaining. Confocal microscopy was used for imaging.
Results: In this study, we found that compared with negative control (NC) group, overexpression of LINC01296 (OE-LINC01296) or TRIP13 (OE-TRIP13) both promoted the proliferation, migration and invasion of SK-N-SH cells, while inhibiting apoptosis; and vice versa. In addition, we further demonstrated that LINC01296 stabilised knockdown via short hairpin RNA (shRNA) (sh-LINC01296) + OE-TRIP13, and TRIP13 stabilised knockdown via shRNA (sh-TRIP13) + OE-LINC01296 decreased SK-N-SH cell proliferation, migration and invasion, while promoting apoptosis. We also established a subcutaneous transplantation tumor model in NB NOD/scid mice, and sh-LINC01296 or sh-TRIP13 inhibited tumor growth in mice, and the tumor growth in the sh-LINC01296 + OE-TRIP13 group and the sh-TRIP13 + OE-LINC01296 group was between the NC group and the sh-LINC01296 or sh-TRIP13 group.
Conclusions: These results suggest that LINC01296 may play a role as an oncogene in the development of tumorigenesis in NB by mediating TRIP13, and provide a marker for the prognosis of NB.
Background: Bladder urothelial carcinoma (BLCA) is a prevalent malignancy with high recurrence rates and limited therapeutic options, necessitating the identification of novel biomarkers for precision medicine. This study investigates the expression and clinical significance of multivesicular body subunit 12B (MVB12B) in BLCA, aiming to evaluate its potential as a prognostic biomarker and therapeutic target.
Methods: We systematically evaluated MVB12B expression across 33 cancer types from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets, and the expression of MVB12B in BLCA was verified using the GSE3167 dataset. Next, the expression of MVB12B in BLCA patients with different clinicopathologic features was analyzed. Then, survival analysis was conducted through the Encyclopedia of RNA Interactomes (ENCORI) database. The receiver operating characteristic (ROC) curves were conducted to assess the diagnostic values of MVB12B. Furthermore, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) was performed to explore potential pathways through which MVB12B might influence BLCA. Finally, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and cellular experiments were used to investigate the role of MVB12B in BLCA.
Results: Our study reported that MVB12B was significantly downregulated in 14 cancer types, particularly in BLCA, in which low expression correlated with advanced tumor stage (III & IV), histological grade (high), and worse overall survival in BLCA patients. PPI networks identified MVB12B's interactions with endosomal sorting complex required for transport (ESCRT) components, and GSEA revealed that MVB12B was significantly involved in keratinization and intermediate filament organization. Experimental validation in clinical samples and BLCA cell lines (T24, UM-UC-3) revealed that MVB12B expression was reduced in tumor tissues and BLCA cell lines. Functional assays demonstrated that MVB12B overexpression suppressed BLCA cell proliferation and migration in vitro, indicating its tumor-suppressive role.
Conclusions: MVB12B functions as a tumor-suppressive role in BLCA and is associated with good prognosis in BLCA patients. MVB12B can be used as a potential biomarker for prognosis and therapeutic of BLCA.
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