Journal of Cancer最新文献

{"title":"Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!","authors":"Emily Charlotte Fretwell, Annwyne Houldsworth","doi":"10.7150/jca.102285","DOIUrl":"https://doi.org/10.7150/jca.102285","url":null,"abstract":"<p><p>Oncolytic viral therapy is a promising treatment for cancer, where 'cold' tumour cells can become 'hot' to the host immune system. However, with few FDA approved therapies, development of new strategies for more cancer types has been slow and relatively unsuccessful in recent years, Combination therapy has been successful for other types of cancer treatment, therefore, may be a viable alternative to improve the efficacy of oncolytic viral therapy which may reduce some of the adverse events of currently used monotherapies, oncolytic virus therapy and chemotherapy being mutually complimentary with each other. Combining oncolytic viruses with immune checkpoint inhibitors provides a significant increase in efficacy when viral therapy was combined with the drug ipilimumab. Phase I and II studies concluded that combination with chemotherapies was safe and effective but did not significantly improve on current monotherapies. Recent experiments suggest that a combination of CAR-T and CAR--M cells is a promising therapeutic approach but needs to advance to clinical testing to observe the human response to the therapy. Viral combination with ipilimumab showed the highest potential for a successful treatment and clinical trials should be advanced to phase III to find conclusive supporting evidence. This review aims to identify and evaluate the potential of currently evolving oncolytic viral therapy with recent advances in genetic engineering providing enhanced oncolytic activity in the tumour, and addressing the lack of host immune responses in 'cold' tumours, with an additional role in enhancing conventional treatment efficacy with combination therapies. The potential of oncolytic viruses to 'turn up the heat' of a tumour microenvironment immunogenicity in combination with other anticancer treatments, provides a promising future for new cancer therapies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 6","pages":"1782-1793"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647866","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":"Addition of Bevacizumab to Vinorelbine-Platinum combination is efficacious in Heavily Pretreated HER2-Negative Metastatic Breast Cancer.","authors":"I-Wei Ho, Yi-Ru Tseng, Chun-Yu Liu, Yi-Fang Tsai, Chi-Cheng Huang, Ling-Ming Tseng, Ta-Chung Chao, Jiun-I Lai","doi":"10.7150/jca.105199","DOIUrl":"10.7150/jca.105199","url":null,"abstract":"<p><p><b>Introduction:</b> Despite rapidly improving therapeutics, challenges remain in the treatment of advanced breast cancer. Vinorelbine, a semisynthetic vinca alkaloid, is effective and well-tolerated in breast cancer treatment. The combination of vinorelbine and platinum-combination is a well-tolerated but underreported chemotherapy regimen. Bevacizumab, a VEGF-neutralizing antibody, has shown efficacy in HER2-negative metastatic breast cancer (mBC) when combined with chemotherapy. In this study we aimed to investigate the clinical and molecular effects of vinorelbine-platinum in heavily pretreated HER2-negative mBC, as well as the impact of adding bevacizumab. <b>Material and methods:</b> We conducted a retrospective study at Taipei Veterans General Hospital to evaluate the effectiveness of the vinorelbine-platinum regimen in heavily pretreated HER2-negative mBC patients from 2016 to 2020, with a portion of patients receiving additional bevacizumab. To model the molecular perturbations at a cellular level, transcriptional profiling of a triple negative breast cancer cell line treated with cisplatin-vinorelbine was done by RNA-sequencing. <b>Results:</b> The cohort included 54 patients. 50% of the patients received ≥ 5 lines of systemic treatment in the metastatic setting. All the patients had received anthracyclines and taxane. In patients treated with vinorelbine-platinum combination, the median progression-free survival (PFS) and overall survival (OS) were 2.3 and 7.3 months, respectively. With bevacizumab, median PFS improved to 4.1 months. Objective response rate (ORR) and disease control rate (DCR) without bevacizumab were 11.1% and 27.7%, respectively, improving to 25% and 83.3% with bevacizumab. Adverse events occurred in 37.0% of patients, with no grade IV events reported. Transcriptional profiling revealed significant downregulation of MAPK pathway, angiogenesis, and growth factor signaling related genes. <b>Conclusion:</b> The vinorelbine-platinum regimen, particularly with bevacizumab, shows potential efficacy even in heavily pretreated HER2-negative metastatic breast cancer patients. Molecular analyses of treated cells highlight potential targets and mechanisms of action, providing a basis for future therapeutic strategies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1726-1735"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483155","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":"KLK7 Involvement in Thyroid Papillary Carcinoma Cell Migration and Invasion by EMT via MAPK/ERK Pathways.","authors":"Min Li, Zi-Wen Li, Jia-Yin Song, Yu Bin, Tao Ni, Gang Xue, Xu Lin, Jing-Fang Wu","doi":"10.7150/jca.101555","DOIUrl":"10.7150/jca.101555","url":null,"abstract":"<p><p><b>Purpose:</b> KLK7, also known as Kallikrein 7, is a secreted enzyme classified as a serine protease. Earlier studies have indicated that KLK7, KLK10, and KLK11 are linked to the survival rates and immune reactions of individuals with papillary thyroid cancer (PTC). This research examines KLK7, investigating its role and expression, and evaluates its viability as a treatment target for PTC. <b>Methods:</b> Initially, we examined the expression and possible functions of KLK7 in PTC using bioinformatics techniques. Researchers examined the impact of KLK7 on the cancer characteristics of PTC and explored if KLK7 influences the Epithelial-mesenchymal transition (EMT) process via the MAPK/ERK pathway in PTC using methods like immunohistochemistry and growth curve analysis. Ultimately, a model using a nude mouse was conducted to confirm the impact of KLK7 on PTC. <b>Results:</b> Our research demonstrated that KLK7 exhibited variations in THCA tissues, and KLK7-related genes had the role of participating in protein synthesis, genetic variation, mRNA degradation and immune microenvironment of PTC. KLK7 was upregulated in PTC tissues and positively associated with clinical stage and lymph node metastasis. Furthermore, the inhibition of KLK7 significantly diminished the proliferation, migration, and invasiveness of PTC cells. Notably, silencing KLK7 reduced phosphorylation of ERK1/2 and suppression of EMT. <i>In vivo</i> experiments further supported these findings. KLK7 might serve as an efficacious therapeutic target and predictive biomarker for PTC patients. <b>Conclusion:</b> KLK7 could be essential in the cancerous advancement of PTC by influencing the EMT via the MAPK/ERK signaling pathway, thereby impacting the growth, migration, and invasiveness of PTC cells. KLK7 appears to be a promising candidate for targeting in PTC therapy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1709-1725"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483171","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":"NUPR1 contributes to endocrine therapy resistance by modulating BIRC5 expression and inducing luminal B-ERBB2⁺ subtype-like characteristics in estrogen receptor-positive breast cancer cells.","authors":"Chun-Hui Lee, Yi-Chen Lin, Yung-Chieh Chang, Pin-Chen Chen, Kai-Hsuan Lin, Tzu-Miao Yeh, Euphemia Yee Leung, I-Li Lin, Shang-Hung Chen, Chun Hei Antonio Cheung","doi":"10.7150/jca.105425","DOIUrl":"10.7150/jca.105425","url":null,"abstract":"<p><p>Acquired resistance to endocrine therapy is a major clinical challenge in the treatment of luminal A [estrogen receptor (ER)⁺ and/or progesterone receptor (PR)⁺, human epidermal growth factor receptor 2 (ERBB2/HER2)^-, and low Ki-67] breast cancer. Recently, molecular subtype conversion has been suggested as one of the possible causes of the development of drug-resistant breast cancer. However, the molecular mechanism underlying the molecular subtype conversion and the induction of endocrine therapy resistance in luminal A breast cancer is still incompletely understood. Here, we found that the ER⁺ MCF7-derived endocrine therapy-resistant MCF7-TamC3 breast cancer cells exhibit increased expression of an intrinsically disordered chromatin protein, NUPR1, compared to the parental luminal-A subtype like MCF7 breast cancer cells. Intriguingly, MCF7-TamC3 cells also exhibit characteristics that resemble the luminal B-ERBB2⁺ breast tumor subtype, like the increased expression of ERBB2 and the increased sensitivity to monoclonal ERBB2-targeting antibody Trastuzumab <i>in vitro</i>. Kaplan-Meier analysis of expression cohorts of breast tumors showed that high <i>NUPR1</i> mRNA expression levels correlate with poor overall and relapse-free survival in both endocrine therapy-treated ER⁺ and ERBB2-enriched breast cancer patients. Results of the bioinformatics analysis showed that the <i>NUPR1</i> mRNA expression level is also correlated with the clinical grading of the Tamoxifen-treated ER⁺ primary breast cancer. The qPCR and the western blot analysis results revealed that NUPR1 positively regulates the expression of the epigenetic regulator HDAC5, the anti-apoptotic molecule BIRC5, and the mitogenic receptor ERBB2 in MCF7-TamC3 and the ERBB2-enriched subtype like SK-BR-3 breast cancer cells. Downregulation of NUPR1 increased the sensitivity to estrogen deprivation in MCF7-TamC3 cells and decreased the viability of SK-BR-3 cells <i>in vitro</i>. These findings indicate that dysregulation of NUPR1 promotes the development of estrogen independence in ER⁺ breast cancer cells in part through expression regulation of HDAC5, ERBB2, and BIRC5. Targeting NUPR1 or its downstream regulating molecules may offer a potential strategy for overcoming resistance to endocrine therapy in patients with ER⁺ breast cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1694-1708"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483288","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":"Characterization of lncRNA-Driven Networks in Portal Vein Tumor Thrombosis: Implications for Hepatocellular Carcinoma Progression.","authors":"Ji Young Kim, So Hee Dho, Lark Kyun Kim","doi":"10.7150/jca.107270","DOIUrl":"https://doi.org/10.7150/jca.107270","url":null,"abstract":"<p><p><b>Background</b>: Portal vein tumor thrombosis (PVTT) is a frequent and serious complication of advanced hepatocellular carcinoma (HCC) that often results in poor prognosis. Although PVTT holds significant clinical relevance, the molecular mechanisms driving its formation are not well understood. Long non-coding RNAs (lncRNAs) have emerged as potential contributors to PVTT progression, prompting this study to explore lncRNAs as potential biomarkers for PVTT. <b>Methods</b>: We analyzed publicly available datasets from the Gene Expression Omnibus to identify differentially expressed lncRNAs and mRNAs across three comparisons: normal vs. HCC, normal vs. PVTT, and HCC vs. PVTT. Transcriptional profiles were characterized, and proteins interacting with HCC- and PVTT-specific lncRNAs were screened using online databases, revealing that all interacting proteins were transcription factors (TFs). We constructed lncRNA-TF-target gene regulatory networks by intersecting TF target genes with differentially expressed genes (DEGs) from each comparison. Protein-protein interaction (PPI) network analysis was performed to identify key clusters and hub genes, with TFs such as AR and ESR1 being highlighted. Gene Ontology analyses were conducted to understand the biological functions of the regulatory networks. <b>Results</b>: The study identified distinct transcriptional profiles for normal, HCC, and PVTT samples. Key regulatory networks, involving lncRNAs, TFs, and target genes, were constructed, and significant hub genes, including AR and ESR1, were identified as potential therapeutic targets. PPI network analysis revealed important clusters associated with PVTT progression, while Gene Ontology analyses provided insights into relevant biological functions. <b>Conclusions</b>: This study presents a novel framework for understanding lncRNA-TF-mediated gene regulation in PVTT. It identifies potential therapeutic targets and prognostic biomarkers that could facilitate the development of targeted therapies for PVTT, offering new opportunities to improve clinical outcomes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 6","pages":"1754-1767"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648704","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":"ADAM10 is a key player in the diagnosis, prognosis and metastasis of non-small cell lung cancer (NSCLC).","authors":"Wenqian Zhang, Liyao Yang, Mufan Li, Lianmei Zhang, Jingliang Cheng, Ali H El-Far, Youhua Xu, Junjiang Fu","doi":"10.7150/jca.107236","DOIUrl":"10.7150/jca.107236","url":null,"abstract":"<p><p>A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) plays critical roles in various cancer-associated biological events, such as cell multiplication, migration, and metastasis. This study employs both the TCGA database and patient samples to demonstrate that ADAM10 is highly expressed in non-small cell lung cancer (NSCLC) compared with normal tissue at different stages. Increased ADAM10 expression is positively correlated with decreased overall and recurrence-free survival. On the functional front, overexpression of ADAM10 promotes lung cancer cell progression, migration, and invasion, whereas downregulation of ADAM10 inhibits these processes. Mechanically, ADAM10 modulates the expression of Notch1, MMP9 and EMT markers such as Vimentin, N-cadherin, and E-cadherin. Overall, our findings suggest that ADAM10 may be a promising therapeutic and prognostic marker for NSCLC, emphasizing the importance of regulating its expression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1736-1746"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483151","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 Impact of <i>MET</i> Variants in Oral Cancer Progression and Clinicopathological Characteristics.","authors":"Ping-Ju Chen, Yen-Ting Lu, Wei-En Yang, Chun-Wen Su, Lun-Ching Chang, Shun-Fa Yang, Chiao-Wen Lin, Ying-Erh Chou","doi":"10.7150/jca.106426","DOIUrl":"10.7150/jca.106426","url":null,"abstract":"<p><p>Epigenetic, genetic predisposition and epidemiological risk factors were suggested to be involved in the carcinogenesis of oral cancer. In this study, we focused on the associations of MET single-nucleotide polymorphisms (SNPs) to oral cancer susceptibility and clinicopathological characteristics. The MET SNPs rs41736, rs41739, rs1621, and rs33917957 in 1198 controls and 1318 male patients with oral cancer were analyzed with real-time polymerase chain reaction. Our results revealed that the cigarette smokers among the oral cancer patients who carried the <i>MET</i> rs1621 polymorphic variant \"G\" were significantly associated with lower risk to develop oral cancer [OR (95% CI) = 0.463 (0.226-0.948)]. The male oral cancer patients who with the genotypic variant \"G\" of <i>MET</i> rs33917957 were associated with lower risk of cell differentiated grade (p = 0.041). In the TCGA database, the MET expressions were upregulated in oral cancer tissues compared to normal tissues, and were correlated with poor cell differentiated and poorer prognoses in smoker groups. In conclusion, these novel findings underscore the role of MET genetic variants in oral cancer susceptibility, particularly in smokers, and highlight the potential of these variants for prognosis and disease prediction.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1747-1753"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483308","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":"System Analysis Identifies MYBL2 As a Novel Oncogene Target for Metastatic Prostate Cancer.","authors":"Renlun Huang, Jing Li, Jiawei Zhu, Wei Deng, Zhichao Wang, Songtao Xiang","doi":"10.7150/jca.107232","DOIUrl":"https://doi.org/10.7150/jca.107232","url":null,"abstract":"<p><p>Bone metastasis significantly contributes to the unfavorable prognosis observed in patients with prostate cancer. MYB proto-oncogene like 2 (MYBL2) has been identified as a potential target gene implicated in tumor progression. Nevertheless, the oncogenic role and underlying mechanisms of MYBL2 in bone metastasis of prostate cancer (PCa) have yet to be elucidated. Bioinformatics analyses were employed to identify genes pivotal to metastatic PCa. Subsequently, a series of molecular biology experiments in vitro, alongside a model of PCa bone metastasis in vivo, were utilized to validate the pro-metastatic effects and underlying mechanisms of MYBL2. A bioinformatics analysis identified a candidate set of 72 genes, which was used to establish a PFS prognostic model highlighting 16 key genes. Based on the expression of these 16 key genes, 498 patients with PCa from the TCGA database were divided into four subgroups. Patients in the C1 and C4 subgroups had poorer prognoses. Through the analysis of sequencing data from the C1 and C4 cohorts in comparison to the C2 and C3 cohorts, we identified MYBL2 as a critical prognostic gene in metastatic PCa. Notably, we found that MYBL2 was significantly expressed in metastatic PCa and positively related to poor prognosis. Mechanistic studies revealed that MYBL2 overexpression promoted PCa cells invasion and EMT, while NOTCH3 knockdown partly abrogated that. Moreover, MYBL2 overexpression can promote PCa xenograft growth and bone metastasis in vivo. This study found that MYBL2 overexpression in PCa were positively related to metastasis and poor prognosis. MYBL2 promoted PCa bone metastasis via activating NOTCH3. Targeting the MYBL2/NOTCH3 axis could help prevent metastatic PCa.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 6","pages":"1768-1781"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648529","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":"Prognostic Significance of CDK1 in Ovarian and Cervical Cancers.","authors":"Cong Xu, Chaowen Chen, Yonghong Xu, Zhenqi Li, Huaqiu Chen, Guangming Wang","doi":"10.7150/jca.104371","DOIUrl":"10.7150/jca.104371","url":null,"abstract":"<p><p><b>Background:</b> Ovarian cancer (OC) and cervical cancer (CC) are the leading causes of death among women. Therefore, identifying markers for early detection and treatment is critical. CDK1 governs the G2/M transition of the cell cycle and is a significant regulatory protein of the cycle. RO-3306 and UBE2C are related to CDK1 expression and might jointly facilitate the development of OC. CDK1 and CDK2 phosphorylate MLK3, which plays an important role in the invasion and proliferation of OC cells. Furthermore, miR-490-3P targets CDK1 and restrains the growth of ovarian tumors. CDK1 also plays a crucial part in the progression of CC. For instance, CDK1 overexpression can rescue the effect of RCC1 knockdown, which is involved in key processes, such as cytoplasmic transport, on G1 cell cycle progression. Using bioinformatics analysis, we evaluated the functional enrichment and role of the co-expressed gene CDK1 in these two cancers and its impact on their prognoses. <b>Methods:</b> First, we screened public datasets for OC- and CC-associated DEGs and identified intersecting genes. Enrichment analyses of these genes revealed key biological pathways and processes. We then generated protein-protein interaction networks to identify central genes and important gene modules. <b>Results:</b> Additional enrichment analyses revealed that cell cycle regulation and germ cell maturation were the primary processes regulated by these core genes. We also examined the function of CDK1 in OC and CC, demonstrating its overexpression and its association with particular immunological cell infiltration patterns. Furthermore, CDK1 mutational burden, copy number variation, and patient survival analyses indicated that CDK1 may be a useful prognostic marker. Finally, immunohistochemical examination confirmed the expression of some candidate genes in clinical samples. <b>Conclusion:</b> These findings shed light on the molecular causes of OC and CC and will aid the identification of novel targets for future research regarding these cancers, including their diagnosis and treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1656-1667"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483302","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":"Identification of a Lactate Accumulation Model to Explain the Heterogeneity in Prognosis, Immune Landscape, and Tumor Environment for HNSCC patients.","authors":"Yi Jin, Xiang Xiao, Jiayu Xiang, Tingjie Yu, Tingting Wang, Yonghong Zhou, Siwei Huang","doi":"10.7150/jca.99560","DOIUrl":"10.7150/jca.99560","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers with a high mortality rate. Lactate accumulation, a hallmark of cancer, has received extensive attention, but its role in HNSCC remains underexplored. Therefore, we identified 33 prognostic genes related to lactate accumulation. By consensus clustering, we separated all HNSCC samples into cluster_A or cluster_B and explored the difference of clinicopathological characteristics and genomics landscape. Next, we performed LASSO analysis and RSF to calculate the lactate-related gene score (LRGS) and constructed a risk model with high accuracy for predicting survival, as estimated by ROC, nomogram, and calibration curve. Then, through OncoPredict algorithm and TCIA, we filter the suitable drugs, especially immunology with diverse LRGS. GSEA analysis showed that the DEGs of LRGS were enriched in activation of immune response and positive regulation of immune response. Moreover, we developed a tumor-infiltrating immune-related lncRNA signature (TILSig) through a combination of 115 immune cell lines from 16 GEO datasets and DealGPL570. Subsequently, we identified the 9 tumor-infiltrating immune-related lncRNAs and calculated the TIL_score. The correlations among these tumor-infiltrating immune-related lncRNAs, hub lactate-related genes and LRGS levels were visualized. According to validation using multiple datasets including TCGA, GSE65858, GSE41613, GSE27020, and the IMvigor 210 database, CARS2, NFU1, and SYNJ1 were identified as hub genes. In light of a comprehensive pan-cancer study, we analyzed these genes to detect the potential clinical value. In conclusion, the constructed LRGS provides important insights for subsequent mechanistic research and can guide clinicians in proposing therapeutic strategies for HNSCC patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 5","pages":"1668-1683"},"PeriodicalIF":3.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483183","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}