Cancer Research and Treatment

Original Articles

Identification of Tumor Doubling Time-Related Subtypes and Construction of Risk Models to Predict Prognosis and Immunological Features in Breast Cancer: Yuehong Xu, Hongbo Li, Lulu Yang, Rongfei Wang; Received August 27, 2025 Accepted December 30, 2025 Published online December 31, 2025; DOI: https://doi.org/10.4143/crt.2025.948 [Accepted]

Abstract PDF: Purpose
Breast cancer (BRCA)'s molecular heterogeneity complicates prognosis and treatment. Tumor Doubling Time (TDT), a critical growth rate metric with clinical and prognostic significance, offers untapped potential as a biomarker to decode heterogeneity and improve therapeutic strategies.
Materials and Methods
Based on transcriptomic and clinical data from TCGA and GEO, this study analyzed BRCA. Through differential expression and survival analyses, differentially expressed tumor doubling time-related genes (TDTRGs) with prognostic significance were identified. Consensus clustering using these genes defined two molecular subtypes. A prognostic risk model was constructed and validated through LASSO and multivariate Cox regression. Comprehensive evaluation was performed on these molecular subtypes and risk groups, encompassing immune infiltration (ssGSEA, CIBERSORT, ESTIMATE), mutational burden, response to immunotherapy (IMvigor210), and drug sensitivity (CellMiner, pRRophetic).
Results
This study constructed and validated an 8 gene prognostic risk model demonstrating robust predictive performance in both training (AUCs: 1-year=0.703, 3-year=0.693, 5-year=0.671) and validation cohorts. The low-risk group showed significantly enhanced immune cell infiltration, elevated immune checkpoint expression, and improved response to immunotherapy. Conversely, the high-risk group displayed increased tumor purity, metabolic reprogramming (e.g., respiratory electron transport), genomic instability, higher tumor mutational burden, and differential drug sensitivity (e.g., resistance to Gemcitabine/Tamoxifen).
Conclusion
This study establishes a novel TDTRGs framework for BRCA molecular classification and validated prognostic stratification. It reveals key disparities in immune microenvironment and genomic stability, enhancing understanding and guiding personalized therapeutic strategies.

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Silence of Transmembrane Channel-Like 5 Inhibits Cell Proliferation, Migration, and Invasion While Promoting Apoptosis Via Deactivating the AKT Pathway in Breast Cancer: Jinnan Wan, Yang Li, Zhimin Liu; Received July 30, 2025 Accepted December 7, 2025 Published online December 9, 2025; DOI: https://doi.org/10.4143/crt.2025.805 [Accepted]

Abstract PDF: Purpose
Transmembrane channel-like 5 (TMC5) plays a tumor-promoting role in the progression of various tumors. However, its effect on regulating breast cancer cell function remains scarce. The current study aimed to evaluate the effect of TMC5 silence on the proliferation, apoptosis, migration, and invasion of breast cancer cell lines.
Materials and Methods
TMC5-specific small interfering RNA (siTMC5) and siNC were transfected into MDA-MB-231 and MCF-7 cell lines; subsequently, the 740Y-P was co-cultured. Then, the proliferation, apoptosis, migration, invasion, and p-AKT expression were determined.
Results
In MDA-MB-231 and MCF-7 cell lines, silence of TMC5 could reduce the proliferation rate at 48 hours (h) and 72 h, migration rate, and invasion rate, while elevate the apoptosis rate. Besides, silence of TMC5 could decrease the p-AKT/AKT expression. The combination of 740Y-P with the silence of TMC5 could reversely increase the proliferation rate at 48h and 72h, migration rate, and invasion rate compared with the silence of TMC5 only. The apoptosis rate showed the opposite trend.
Conclusion
The silence of TMC5 could inhibit the proliferation, migration, and invasion while promoting the apoptosis of breast cancer, while more in vivo validation is needed to explore its potential to be a treatment target for patients with breast cancer.

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Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma: Xin-Yi Zhang, Tong-Yao Xing, Wei Hua, Yue Li, Yi-Lin Kong, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Hua Yin, Li Wang, Jian-Yong Li, Rui Gao, Jin-Hua Liang, Wei Xu; Received April 14, 2025 Accepted August 29, 2025 Published online September 1, 2025; DOI: https://doi.org/10.4143/crt.2025.420 [Accepted]

Abstract PDF: Purpose
This study investigates the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and explores the underlying biological mechanisms, focusing on immune regulation and cellular metabolism.
Materials and Methods
We included 2,590 DLBCL patients from 7 publicly databases (integrated cohort) and 202 additional DLBCL cases from our institution (JSPH cohort). Next-generation sequencing (NGS) was used to detect SOCS1 mutations in DLBCL patients. We analyzed the association between these mutations and overall survival (OS) and progression-free survival (PFS). Additionally, we examined how SOCS1 mutations might influence immune responses, cellular metabolism, and signaling pathways, particularly in the ST2 subtypes of DLBCL.
Results
In the integrated cohort, 15.1% of patients carried SOCS1 mutations, with 12.3% of these mutations located in the SOCS-BOX domain. SOCS1 mutations were found to be more frequent in the GCB and ST2 subtypes of DLBCL. In the integrated cohort, patients with SOCS1 mutations had significantly better OS (p=0.015) and PFS (p=0.007). Mutations located in the SOCS-BOX domain were associated with even better OS (p=0.015) and PFS (p=0.012). In the JSPH cohort, transcriptomic analyses indicated enhanced interferon signaling, immune activation, and downregulation of metabolic pathways in SOCS1-mut cases, especially within the ST2 subtype. These alterations may contribute to a more favorable tumor microenvironment and improved clinical outcomes.
Conclusion
SOCS1 mutations, particularly those in the SOCS-BOX domain, are associated with improved prognosis in DLBCL. By promoting immune activation and inhibiting cellular metabolism, these mutations may not only serve as prognostic biomarkers but also provide insights into potential therapeutic avenues.

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BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma: Chun-Yu Shang, Wei Hua, Tong-Yao Xing, Kai-Xin Du, Yi-fan Wu, Yue Li, Hua Yin, Hao-Rui Shen, Li Wang, Jian-Yong Li, Rui Gao, Wei Xu, Jin-Hua Liang; Received May 8, 2025 Accepted July 30, 2025 Published online July 30, 2025; DOI: https://doi.org/10.4143/crt.2025.494 [Accepted]

Abstract PDF: Purpose
B celltranslocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The speciﬁc enrichment of BTG1 mutation (BTG1^mut) raises a potential hypothesis that they may actively contribute to DLBCL. However, the biological characteristics and prognostic significance of BTG1 in DLBCL remain to be explored. Therefore, the objective of our study was to evaluate the value of BTG1 in DLBCL.
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Tumor tissue samples of DLBCL patients diagnosed in Jiangsu Province Hospital (JSPH) from 2021 to 2023 were collected for NGS, 195 samples were analyzed the gene expression levels using RNA-seq, among them, 40 samples were analyzed by untargeted metabolomic.
Results
We enrolled 2,379 DLBCL patients from 5 published studies and 243 DLBCL patients from Jiangsu Province Hospital (JSPH) cohort. 11.0% (262/2379) of patients were BTG1^mut in external cohort, compared with 25.1% (61/243) in the JSPH cohort. BTG1^mut was associated with adverse clinical features and was prone to involve testis. Patients with BTG1^mut exhibit inferior overall survival (OS). Furthermore, pathway enrichment analysis of the untargeted metabolomic showed that several meaningful pathways have been found such as amino acid metabolism and lipid metabolism.
Conclusion
BTG1 mutation was promising prognostic predictor for DLBCL. The mechanism driving different survival outcomes may be attributed to the tumor metabolic reprogramming.

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A Novel CD58 Mutation–Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients: Hui-Li Wang, Chun-Yu Shang, Wei Hua, Hua Yin, Yue Li, Jun-Heng Liang, Rui Gao, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Li Wang, Jian-Yong Li, Jin-Hua Liang, Wei Xu; Received November 27, 2024 Accepted July 21, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1143 [Epub ahead of print]

Abstract PDF Supplementary Material

Purpose
CD58, a ligand of the CD2 receptor on T cells and natural killer cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58^mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58^mut in DLBCL patients.
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3,025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform next-generation sequencing and gene expression was analyzed via RNA-seq.
Results
We found that 8.2% (250/3,025) of patients were CD58^mut in integrated cohort, whereas 11.4% (23/202) in the JSPH cohort. CD58^mut patients exhibit inferior progression-free survival (the integrated cohort: hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.77 to 1.20; p=0.663 the JSPH cohort: HR, 1.85; 95% CI, 0.85 to 4.04; p=0.052) and overall survival (the integrated cohort: HR, 1.43; 95% CI, 1.15 to 1.77; p < 0.001; the JSPH cohort: HR, 2.40; 95% CI, 0.83 to 6.93; p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1, and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58^mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages.
Conclusion
Our results indicated that CD58^mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.

Citations

Citations to this article as recorded by

Lipid Metabolism Reprogramming in Diffuse Large B-Cell Lymphoma (DLBCL): Mechanisms and Treatment Strategies
Yue-E Ding, Yi-Ran Zhong, Lai-Shun Zhang, Lei Xu, Jia Li, Yi Wen
Cancers.2026; 18(4): 701. CrossRef
ESAE-SDA: ensemble sparse autoencoder framework for epigenomics-informed snoRNA-disease associations prediction
Xinqing Jiang, Xiaojun Chen, Lifeng Xu, Feng Zhang, Jiawei Chen, Wenqian Zhang
BMC Bioinformatics.2025;[Epub] CrossRef

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Uptake of Ga-67 by Cultured Cells: Transferrin-dependent and Transferrin-independent Mechanisms: Myung Hee Sohn, Seok Tae Lim, Jae Yong Kwak, Chang Yeol Yim; J Korean Cancer Assoc. 2000;32(4):742-749.

Abstract PDF: PURPOSE
We determined whether the uptake of Ga-67 by cultured cells occur by both transferrin (Tf)-dependent and independent mechanisms and the mechanism and magnitude of its uptake may vary as the degree of expression of the transformed phenotype.
MATERIALS AND METHODS
Uptake of Ga-67 between the tansformed and untransformed cells was compared. Cells were incubated with Ga-67 in either the presence or absence of Tf and with complete medium containing Ga-67 after preincubating with anti-Tf receptor antibodies at 37oC in 8% CO2. Monolayers of cells were washed and trypsinized. Radioactivity and protein content of the samples were determined.
RESULTS
Uptake of Ga-67 by cultured cells occurred both in Tf-bound and ionic form and was increased with radioactivity and time. The magnitude for the uptake of Tf-bound form was approximately 3 and 6-fold greater than ionic form. In the presence of Tf, uptake of Ga-67 was 2-fold greater in the transformed cells. Conversely, In the absence of Tf, it was 1.5-fold greater in the untransformed cells. Regardless of blocking the Tf receptor by anti-Tf receptor antibodies, a significant amount of intracellular Ga-67 uptake was found.
CONCLUSION
Dual mechanisms exist for the uptake of Ga-67 by cultured cells. The primary important one was the Tf-dependent system. Tf-dependent and independent mechanisms and the magnitude operated oppositely in the transformed cells when compared to their untransformed counterpart.

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