{"title":"Lymph Node Ratio (LNR) Discriminates Prognostication in pN1a-b and pN2 Stage-III Colon Cancer.","authors":"Erman Akkus, Mehmet Kayaalp, Beliz Bahar Karaoğlan, Cihangir Akyol, Güngör Utkan","doi":"10.7150/jca.104336","DOIUrl":"10.7150/jca.104336","url":null,"abstract":"<p><p><b>Background:</b> The lymph node ratio (LNR), involved nodes/ lymph nodes examined, is associated with survival in colon cancer. Previous studies investigated the prognostic role of LNR regardless of TNM N staging or compared LNR and TNM N stages for prognostic strength. However, LNR may be utilized to obtain additional prognostic information rather than replacing TNM staging in daily practice. This study aimed to evaluate the role of LNR in TNM N stages to provide further prognostic information in daily practice. <b>Methods:</b> Patients with stage-III colon cancer who underwent surgery and adjuvant chemotherapy were included. pN1c tumors (tumor deposits without node involvement) and rectal cancers were excluded. Clinicopathological parameters and LNR in pN1a-b and pN2 groups were evaluated for recurrence-free survival (RFS). <b>Results:</b> A total of 97 patients were included [pN1a-b: n=69 (71.1%) and pN2: n=28 (28.9%)]. Median LNR in the entire population was 0.09 (0.01-0.84) with a median lymph node examined of 22 (8-89) and involved of 2 (1-17). Median RFS was not reached in the pN1a-b and pN2 groups during a median follow-up of 20.8 months (1.13-101.03), with significantly better survival of the pN1a-b group (p=0.003). Among the pN1a-b group, the LNR cut-off was set as 0.10. LNR significantly discriminated RFS (Median not-reached, p=0.001). Among the pN2 group, the LNR cut-off was set as 0.25 and LNR significantly discriminated RFS [Not reached vs. 11.40 months (95%CI: 3.57-16.83), p=0.004]. Combined pN-LNR groups revealed significant discrimination in RFS (p<0.001). RFS was not statistically different between pN2-LNR≤0.25 and pN1-LNR>0.10 groups (p=0.282). In multivariable analysis with clinicopathological parameters, only LNR was significant (p=0.023), whereas the pN stage did not remain significant (p=0.637). <b>Conclusion:</b> LNR adds further prognostication in pN1a-b and N2 groups. LNR may be utilized to detect patient subgroups in different TNM N sages (pN1a-b and pN2) but with similar prognoses. This further prognostic information may assist clinical decisions in practice. The results of this study emphasize an adequate and higher number of lymph node samples in surgery.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 4","pages":"1032-1039"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hesperidin inhibits colon cancer progression by downregulating SLC5A1 to suppress EGFR phosphorylation.","authors":"Xiaodong Li, Zhao Wu, Lebin Yuan, Xing Chen, He Huang, Fei Cheng, Wei Shen","doi":"10.7150/jca.104867","DOIUrl":"https://doi.org/10.7150/jca.104867","url":null,"abstract":"<p><p><b>Objective:</b> Hesperidin, an active constituent of traditional Chinese medicine, Chenpi, exhibits anticancer properties across different cancers. This study aimed to clarify the efficacy of Hesperidin against tumors and its mechanisms of action in colon cancer. <b>Method</b>: We assessed the efficacy of Hesperidin on human colon cancer cells (HCT-116 and DLD-1) and normal colonic epithelial cells (NCM460). We quantified cell viability at various Hesperidin concentrations using the CCK8 assay in a series of experiments. We employed clone formation, EdU incorporation, Transwell, and wound healing assays to clarify Hesperidin efficacy on cancer cell proliferation, invasion, and migration. Western blot analyses revealed modulations in epithelial-mesenchymal transition-related proteins, SLC5A1, EGFR, and phosphorylated EGFR levels following Hesperidin exposure. Co-IP assays further validated the interaction between SLC5A1 and EGFR. Our findings were significantly restored following SLC5A1 overexpression in colon cancer cells, highlighting its pivotal role in Hesperidin-induced responses. <b>Results</b>: Hesperidin selectively impaired the viability of HCT-116 and DLD-1 colon cancer cells at specific concentrations while preserving normal NCM460 cells. This flavonoid dose-dependently reduced cancer cell proliferation, migration, and invasion. It significantly suppressed SLC5A1 and phosphorylated EGFR expression. We identified a direct SLC5A1-EGFR interaction essential for regulating EGFR activity in colon cancer. Overexpressing SLC5A1 significantly reduced the inhibitory effects of Hesperidin, highlighting its crucial role in this context. <b>Conclusion:</b> Hesperidin exerts its anticancer effects on colon cancer by inhibiting SLC5A1 expression and consequently downregulating EGFR phosphorylation.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 3","pages":"876-887"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sup Kim, Kyung Hwan Kim, Hee-Won Jung, Eun-Oh Jeong, Han-Joo Lee, Jeanny Kwon, Hyon-Jo Kwon, Seung-Won Choi, Hyeon-Song Koh, Seon-Hwan Kim
{"title":"Elevated Serum IL-6 as a Negative Prognostic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Validation.","authors":"Sup Kim, Kyung Hwan Kim, Hee-Won Jung, Eun-Oh Jeong, Han-Joo Lee, Jeanny Kwon, Hyon-Jo Kwon, Seung-Won Choi, Hyeon-Song Koh, Seon-Hwan Kim","doi":"10.7150/jca.104759","DOIUrl":"https://doi.org/10.7150/jca.104759","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, necessitating the discovery of reliable serum prognostic biomarkers. This study aimed to investigate the prognostic value of serum Interleukin-6 (IL-6) in GBM patients. <b>Methods:</b> Bioinformatics analysis via gene set enrichment analysis was conducted on The Cancer Genome Atlas RNA-seq data to explore the pathways enriched in samples with high <i>IL-6</i> expression. The Tumor IMmune Estimation Resource database was used to analyze the association between <i>IL-6</i> expression and immune cell infiltration. To validate the role of IL-6 in a clinical setting, a retrospective cohort study was conducted on newly diagnosed GBM patients. Serum IL-6 levels were repeatedly measured at key milestone time points, and their correlation with survival data was analyzed. <b>Results:</b> Bioinformatics analysis revealed that high <i>IL-6</i> expression is associated with the activation of procancer pathways, that there is a positive correlation between <i>IL-6</i> expression and immune cell infiltration in GBM. Between March 2021 and September 2023, 36 GBM patients and their serum IL-6 measurements at various time points were included in the clinical data analyses. Elevated serum IL-6 levels at baseline, with a cutoff of 7pg/mL, were identified in 11 patients (30.6%). In the multivariate analyses for overall survival (OS), elevated IL-6 was a significant risk factor (p = 0.048), along with unfavorable surgical resection (p = 0.039) and O6-methylguanine-DNA methyltransferase promotor unmethylation (p = 0.027). The median actuarial OS of the high initial IL-6 group was significantly shorter than that of the low initial IL-6 group (6.4 vs. 19.7 months, p < 0.001). However, IL-6 levels at other time points were not related to patient prognosis. <b>Conclusion:</b> Elevated <i>IL-6</i> mRNA expression is correlated with the activation of procancer pathways, increased immune cell infiltration, and poor prognosis in GBM patients. In addition, elevated serum IL-6 at baseline is a negative prognostic factor confirmed in a clinical study. Serum IL-6 may be a potential prognostic biomarker enhancing the management of GBM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 3","pages":"802-811"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fanjun Zeng, Yucheng Huang, Bin Xu, Lintong Yao, Yiqing Zhang, Zhiping Gao, Yingli Luo
{"title":"A Novel Oncolytic Virus Formulation Based on Mesenchymal Stem Cell-Derived Vesicles for Tumor Therapy.","authors":"Fanjun Zeng, Yucheng Huang, Bin Xu, Lintong Yao, Yiqing Zhang, Zhiping Gao, Yingli Luo","doi":"10.7150/jca.104066","DOIUrl":"https://doi.org/10.7150/jca.104066","url":null,"abstract":"<p><p>Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells. MSC vesicles possess natural tumor homing ability and biocompatibility, which can enhance the targeting, uptake, and therapeutic effects of OVs on tumor cells. Experimental results indicated that this treatment system has increased the apoptosis of tumor cells. Furthermore, flow cytometry analysis demonstrated that the uptake of tumor cells by OVs coated with MSC vesicles soared away compared to uncoated OVs, being 1.5 times than that of the uncoated group. Additionally, the confocal laser scanning microscopy also showed that the fluorescence intensity within tumor cells pretreated with MSC-coated OVs was greater. Meanwhile, propidium iodide (PI) staining revealed that MSC-coated Ovs exposed to tumor cells accelerating the apoptosis of the latter. According to the statistics, the number of dead cells was increased, and the flow cytometry testified that the apoptosis in the MSC-coated OV group was as high as 23.78%. These findings highlight the potential of MSC vesicle-coated OVs in enhancing the delivery and efficacy of oncolytic virus therapy, providing a promising strategy for cancer treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 3","pages":"700-707"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuchuan Jiang, Jiejian Chen, Lin Xu, Lin Lv, Xiaoning Gan
{"title":"Development of a Novel four-gene Model for Monitoring the Progression from Metabolic Dysfunction-associated Steatotic Liver Disease to Hepatocellular Carcinoma in Males.","authors":"Yuchuan Jiang, Jiejian Chen, Lin Xu, Lin Lv, Xiaoning Gan","doi":"10.7150/jca.100724","DOIUrl":"https://doi.org/10.7150/jca.100724","url":null,"abstract":"<p><p>The pathogenesis of metabolic dysfunction-associated steatotic liver disease-associated hepatocellular carcinoma (MASLD-HCC) is complex and exhibits sex-specific differences. Effective methods for monitoring MASLD progression to HCC are lacking. Transcriptomic data from liver tissue samples sourced from multiple public databases were integrated. Utilizing both differential expression analysis and robust rank aggregation analysis, differentially expressed genes (DEGs) in patients with MASLD-HCC were identified. Based on these DEGs, diagnostic prediction models for MASLD (DP.MASLD) and HCC (DP.HCC) were constructed using elastic net analysis for various comparisons, including steatosis versus normal, steatohepatitis versus steatosis, and cancer versus non-cancer. Weighted gene correlation network analysis and gene set enrichment analysis were conducted to unveil the underlying pathogenesis of MASLD-HCC in males. Five overlapping DEGs with diagnostic significance in the progression from MASLD to HCC were identified, namely, <i>AKR1B10</i>, <i>CYR61</i>, <i>FABP4</i>, <i>GNMT</i>, and <i>THBS1</i>. DP.HCC demonstrated excellent predictive accuracy, with an area under the curve of 0.910 in the training group and 0.981 in the validation group. Similarly, DP.MASLD showed robust predictive accuracy. The pathogenesis of MASLD-HCC in males primarily involves extracellular matrix-receptor interaction, DNA replication, cell cycle, and T-cell receptor signaling. Overall, our study provides a quantitative assessment tool for the early detection and monitoring of MASLD-HCC, highlighting the male-specific molecular characteristics involved in its progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 3","pages":"917-931"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenjuan Ma, Jiawei Lin, Rongyao Ma, Yang Bai, Di Wu, Xiuyan Zhang, Haixia Zhou, Yun Zhao, Lei Zhang
{"title":"Insights into Structure and Function of Growth Arrest Specific 2 (GAS2).","authors":"Wenjuan Ma, Jiawei Lin, Rongyao Ma, Yang Bai, Di Wu, Xiuyan Zhang, Haixia Zhou, Yun Zhao, Lei Zhang","doi":"10.7150/jca.102893","DOIUrl":"10.7150/jca.102893","url":null,"abstract":"<p><p>Growth arrest specific 2 (GAS2) is a microfilament-associated protein, which is widely distributed in human tissues. It exerts a pivotal influence on various cellular processes, including cytoskeletal regulation, cell cycle progression, apoptosis, and senescence. GAS2 has a dual function in cancer cell growth: on the one hand, it enhances the sensitivity of cancer cells to chemoradiotherapy and prevents malignant transformation of normal cells; but on the other hand, it maintains the growth of cancer cells. GAS2 regulates the cellular activity of Calpain-2, a calcium-dependent protease, by acting as an endogenous inhibitor of the enzyme. The N-terminus of GAS2 binds to Calpain-2, while its C-terminus acts as an inhibitor of the protease activity of Calpain-2. The functional outcome of GAS2 is highly dependent on the specific substrates of Calpain-2 and cellular environment, particularly within tumor cells. Despite garnering increasing attention and a growing body of related research, a systematic review of GAS2 remains absent. This review aims to elucidate the structural and functional aspects of GAS2, with a particular emphasis on its implications in cancer. By comprehensively detailing its role and research progress in malignancies, this review endeavors to furnish novel insights for enhancing the therapeutic strategies against diseases, particularly cancers.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"146-156"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The association between the polymorphism of RAR related orphan receptor beta and the clinical manifestations of oral squamous cell carcinoma.","authors":"Wei-En Yang, Chiao-Wen Lin, Yi-Tzu Chen, Chun-Wen Su, Chia-Ming Yeh, Chia-Yi Lee, Shun-Fa Yang, Mu-Kuan Chen","doi":"10.7150/jca.103945","DOIUrl":"10.7150/jca.103945","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) affects a substantial proportion of the Asian population and is influenced by various genetic risk factors. The <i>RAR-related orphan receptor beta</i> (<i>RORB</i>), a regulator of the circadian rhythm, has been implicated in certain neoplasms. Accordingly, this study investigated the association between <i>RORB</i> single-nucleotide polymorphisms and clinical manifestations of OSCC. A total of 1174 male patients without OSCC and 1254 male patients with OSCC were included in the study. Three <i>RORB</i> single-nucleotide polymorphism loci-rs3750420 (T/C), rs10781247 (A/G), and rs17611535 (C/T)-were genotyped using TaqMan allelic discrimination assays. <i>RORB</i> single-nucleotide polymorphism rs10781247 variants were significantly associated with moderate to poor cellular differentiation in patients with OSCC (<i>p</i> = 0.042). Additionally, among betel quid chewers with OSCC, rs10781247 variants were significantly associated with moderate to poor cell differentiation (<i>p</i> = 0.036). The rs3750420 variants were significantly associated with larger tumor size in individuals with buccal mucosa cancer (<i>p</i> = 0.036). An analysis of Cancer Genome Atlas data revealed that <i>RORB</i> mRNA levels were significantly higher in patients with head and neck squamous cell carcinoma compared with controls (<i>p</i> = 0.0002). Moreover, <i>RORB</i> mRNA levels were significantly higher in stage IV tumors than in stage III tumors (<i>p</i> = 0.0252). In conclusion, <i>RORB</i> single-nucleotide polymorphisms rs3750420 and rs10781247 are associated with adverse clinical characteristics in OSCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 2","pages":"498-505"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive analysis of genomic alterations and novel prognostic biomarkers, and establishment of prediction models of metastasis in metastatic non-small cell lung cancer.","authors":"Kangwei Wang, Meifeng Ye, Zexun Mo, Xiaomei Huang, Yujun Li, Shuquan Wei","doi":"10.7150/jca.97070","DOIUrl":"10.7150/jca.97070","url":null,"abstract":"<p><p><b>Introduction:</b> Most patients with non-small cell lung cancer (NSCLC) have metastases at initial diagnosis. However, the comprehensive molecular characteristics and factors associated with its metastases are still needed. <b>Methods:</b> Tumor sequencing of 556 cancer-related genes was performed on 114 Chinese NSCLC patients. A distinct genomic profile was identified in metastatic patients compared to those without metastases. Kaplan-Meier method was used to analyze the associations between clinical outcomes, clinical characteristics, and mutated genes. The Fisher test and Lasso logistic regression analysis were employed to identify factors related to metastasis and to develop prediction models. <b>Results:</b> Male, squamous cell lung carcinoma, and smokers showed strikingly higher TMB levels in all NSCLCs. The metastatic group had a significantly higher proportion of patients aged ≥ 70 years and in stage III-IV. <i>TP53</i> was the most frequent mutation in both groups, and <i>EGFR</i> tended to be higher in the metastatic group. The copy number variation events occurred more frequently in the metastatic group. Additionally, predictive models for metastasis (AUC = 0.828), pleural metastasis (AUC = 0.582), and multisite metastasis (AUC = 0.559) were established. Females, and <i>EGFR</i> +, <i>ASXL2-</i>, and <i>STK11-</i> cases had better overall survival (OS). Lung adenocarcinoma, and <i>KMT2D-</i> and <i>STK11-</i> cases had better progression-free survival (PFS). NSCLC metastasis was associated with poor OS and poor PFS. <b>Conclusions:</b> Our study provided a comprehensive analysis of genomic alterations in metastatic NSCLCs, identified novel prognostic biomarkers, and provided three predictive models for metastasis, which may have potential implications for personalized treatment strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"339-350"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin Sun, Anni Yu, Yang Yang, Zhiruo Wang, Wenqian Wang, Lan Luo
{"title":"Exploring the Role of Thioredoxin system in Cancer Immunotherapy.","authors":"Lin Sun, Anni Yu, Yang Yang, Zhiruo Wang, Wenqian Wang, Lan Luo","doi":"10.7150/jca.98306","DOIUrl":"10.7150/jca.98306","url":null,"abstract":"<p><p><b>Purpose:</b> The thioredoxin (Trx) system is integral to redox regulation and participates in several physiological processes, including tumor growth, immune response, and stem cell differentiation. We have performed a comprehensive and holistic analysis of the Trx system in tumor immunity in this study. <b>Methods:</b> A study using the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases was conducted to determine the expression and distribution of Trx system proteins. To explore and validate the correlation between Trx system expression levels and tumor progression, GTEx and TCGA datasets were used. Western blotting was used to measure Trx system expression in lung cancer cell lines, while MTT assays were used to measure cell proliferation. The Kaplan-Meier plotter database was used to explore the association between the Trx system and survival outcome of patients in pan-cancer. GO and KEGG enrichment analyses of the Trx system were performed. Next, we analyzed how the Trx system related to immune activation. Using TIDE and TISMO databases, we predicted immunotherapy responses. <b>Results:</b> An abnormal expression of the Trx system is observed in cancer cells. Interference with the Trx system with siRNA or inhibitors significantly inhibits tumor cell growth, suggesting the Trx system is crucial to tumor growth. Through a broad cohort of different cancer types, we explored the prominent role of genes in the Trx system. The Trx system showed a relatively consistent aberrant expression in pan-cancer, correlated closely with clinical prognosis. Interestingly, the Trx system was highly correlated with the clinical prognosis in pan-cancer, as well as immunity and metabolism. The abnormal expression of the thioredoxin system was positively correlated with the expression of genes associated with immune infiltration and with a decrease in survival. The Trx system was also associated with immune response to immunotherapy. <b>Conclusion:</b> The Trx system is a good predictor of both survival and the efficacy of immunotherapy, as well as clinical prognosis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 1","pages":"66-80"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}