Translational cancer research最新文献

{"title":"Copper metabolism-related lncRNAs predict prognosis and immune landscape in liver cancer patients.","authors":"Rui Luo, Shu Huang, Xiaomin Shi, Huan Xu, Jieyu Peng, Wenjie Lei, Shiqi Li, Wei Zhang, Lei Shi, Yan Peng, Xiaowei Tang","doi":"10.21037/tcr-24-611","DOIUrl":"10.21037/tcr-24-611","url":null,"abstract":"<p><strong>Background: </strong>Characterized by its high mortality and easy recurrence, hepatocellular carcinoma (HCC) poses significant clinical challenges. The association between copper metabolism and development of cancer has been identified. However, the underlying mechanisms of copper metabolism-related long non-coding RNAs (CMRLs) in HCC remain elusive. To address the gap, our study analyzed the prognostic and immuno-therapeutic value of CMRLs in HCC.</p><p><strong>Methods: </strong>This research utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data (n=424) for analysis, applying the \"limma\" package in R software for differential gene analysis and construction of a prognostic signature. We validated the signature using training and validation groups stochastically divided at a ratio of 1:1 and assessed prognostic value via Kaplan-Meier, C-index, and receiver operating characteristic (ROC) curves. By multivariate Cox regression, independent prognostic indicators were identified, and a nomogram was formulated for survival forecasting. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated biological pathways, and the immune landscape was examined through multiple algorithms. Finally, drug sensitivity was determined from Genomics of Drug Sensitivity in Cancer (GDSC), with mutation analysis conducted via maftools.</p><p><strong>Results: </strong>In this study, a predictive model based on four pivotal CMRLs (<i>PRRT3-AS1</i>, <i>AC108752.1</i>, <i>AC092115.3</i>, <i>AL031985.3</i>) significantly associated with HCC progression and prognosis was constructed and validated with the overall survival (OS) prediction area under the curve (AUC) values for 1, 3, and 5 years of 0.718, 0.688, and 0.669, respectively. The calibration curves and C-index values showed a solid prognostic ability of the nomogram. The high-risk group was notably higher than the low-risk group both in OS and tumor mutational burdens (TMBs). Moreover, functional annotation enrichment analysis of CMRLs revealed that the signature was mainly associated with mitotic function, chromosome, kinetochore, cell cycle, and oocyte meiosis. Furthermore, therapeutic drugs, including fluorouracil, afatinib, alpelisib, cedranib, crizotinib, erlotinib, gefitinib, and ipatasertib, were found to induce higher sensitivity in high-risk group.</p><p><strong>Conclusions: </strong>The prognostic signature consisting of four CMRLs displays an outstanding predictive performance and improves the precision of immuno-oncology.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5784-5800"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining new disulfidptosis-associated lncRNA signatures pertinent to breast cancer prognosis and immunological microenvironment.","authors":"Yifan Zheng, Yufeng Lin, Yongcheng Zhang, Shangjie Liu, Yongxia Yang, Wenbin Huang","doi":"10.21037/tcr-24-513","DOIUrl":"10.21037/tcr-24-513","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis is a novel form of cell death triggered by disulfide stress that may have important implications for breast cancer (BC) pathogenesis. Nevertheless, studies identifying disulfidptosis-associated long non-coding RNAs (lncRNAs) in BC have not been reported. This study aimed to investigate the prognostic potential of disulfidptosis-related lncRNAs in BC.</p><p><strong>Methods: </strong>RNA-sequencing data and clinical information of BC patients were obtained from The Cancer Genome Atlas (TCGA) database. The lncRNAs associated with disulfidptosis were identified through co-expression analysis. Subsequently, a risk signature consisting of 10 lncRNAs was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses, and its predictive power was validated.</p><p><strong>Results: </strong>The risk signature was found to be an independent prognostic factor for BC patients. Notably, the two subgroups defined by the risk signature exhibited different mutant gene profiles, and risk scores were significantly correlated with tumor mutation burden (TMB). Additionally, single-sample gene set enrichment analysis (ssGSEA) and immune checkpoint analyses indicated that the predicted trait was significantly associated with the immune status of BC patients. Furthermore, 55 potential anticancer drugs were identified that were associated with the signature.</p><p><strong>Conclusions: </strong>In this study, we successfully developed a prognostic model based on disulfidptosis-related lncRNAs, which enhances the accuracy of predicting the prognosis of BC patients. This model also offers a potential target and theoretical foundation for BC treatment, laying a robust groundwork for future research on the functional roles of disulfidptosis-associated lncRNAs in BC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5815-5829"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The usefulness of Hinotori™ which is a surgical support robot system developed in Japan and a challenging case of robot-assisted surgery.","authors":"Takuya Koie","doi":"10.21037/tcr-24-1735","DOIUrl":"10.21037/tcr-24-1735","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5723-5724"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape and prognostic significance of oncogene drivers in metastatic castration sensitive prostate cancer.","authors":"Theodore Wang, Jongmyung Kim, Ritesh Kumar, Rebecca A Deek, Ryan Stephenson, Tina Mayer, Biren Saraiya, Saum Ghodoussipour, Thomas Jang, David Golombos, Vignesh Packiam, Ronald Ennis, Lara Hathout, Salma K Jabbour, Ozan Guler, Cem Onal, Matthew P Deek","doi":"10.21037/tcr-24-123","DOIUrl":"10.21037/tcr-24-123","url":null,"abstract":"<p><strong>Background: </strong>Tumor suppressors are well known drivers of cancer invasion and metastasis in metastatic castration sensitive prostate cancer (mCSPC). However, oncogenes are also known to be altered in this state, however the frequency and prognosis of these alterations are unclear. Thus, we aimed to study the spectrum of oncogene mutations in mCSPC and study the significance of these alteration on outcomes.</p><p><strong>Methods: </strong>Four hundred and seventy-seven patients with mCSPC were included who underwent next generation sequencing. Oncogene alterations were defined as mutations in <i>ALK, AKT1-3, BRAF, CCND1-3, CTNNB1, EGFR, ERBB2, FGFR1, FGFR2, HRAS, KRAS, MDM2, MET, MITF, MYC, NOTCH1-3, NRAS, PIK3CA, PI3KCB, PIK3R1, RET.</i> Endpoints of interests were radiographic progression-free survival (rPFS), time to development of CRPC (tdCRPC), and overall survival (OS). Kaplan Meier analysis was performed and Cox regression hazard ratios (HR) calculated.</p><p><strong>Results: </strong>A total of 477 patients were included with baseline characteristics with 117 patients (24.5%) harbored a mutation within an oncogene. A total of 172 oncogene mutations were found within the population with the most common being <i>MYC</i> (n=29; 16.9%), <i>PIK3CA</i> (n=24; 14%), <i>CTNNB1</i> (n=22, 12.8%), <i>BRAF</i> (n=10, 5.8%), and <i>CCND1</i> (n=10, 5.8%). Oncogene mutations were associated with inferior rPFS (19.2 <i>vs.</i> 32.2 months, P=0.03), tdCRPC (15.7 <i>vs.</i> 32.4 months, P<0.001), and OS (5-year OS 75.3% <i>vs.</i> 55.4%, P=0.01). On multivariable analysis oncogene mutations were strongly associated with tdCRPC (HR 1.42, P=0.03).</p><p><strong>Conclusions: </strong>Oncogenes are frequency mutated in mCSPC and associated with aggressive features and inferior outcomes. Future work will need to validate these results to better assess its significance in allowing for personalization of care.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6235-6245"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics and machine learning approach reveals tumor microenvironment-associated prognostic biomarkers in ovarian cancer.","authors":"Wenzhi Jiao, Shasha Yang, Yue Li, Yu Li, Shanshan Liu, Jianwei Shi, Minmin Yu","doi":"10.21037/tcr-24-539","DOIUrl":"10.21037/tcr-24-539","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a globally prevalent malignancy with significant morbidity and mortality, yet its heterogeneity poses challenges in treatment and prognosis. Recognizing the crucial role of the tumor microenvironment (TME) in OC progression, this study leverages integrative multi-omics and machine learning to uncover TME-associated prognostic biomarkers, paving the way for more personalized therapeutic interventions.</p><p><strong>Methods: </strong>Employing a rigorous multi-omics approach, this study analyzed single-cell RNA sequencing (scRNA-seq) data from OC and normal tissue samples, including high-grade serous OC (HGSOC) from the Gene Expression Omnibus (GEO: GSE184880) and The Cancer Genome Atlas (TCGA) OC cohort, utilizing the Seurat package to annotate 700 TME-related genes. A prognostic model was developed using the least absolute shrinkage and selection operator (LASSO) regression and independently validated against similarly composed HGSOC datasets. Comprehensive gene expression and immune cell infiltration analyses were conducted, employing advanced algorithms like xCell to delineate the immune landscape of HGSOC.</p><p><strong>Results: </strong>Our investigation unveiled distinctive immune cell infiltration patterns and gene expression profiles within the TME of HGSOC. Notably, the prevalence of exhausted CD8⁺ T cells in high-risk patient samples emerged as a critical finding, underscoring the dualistic nature of the immune response in OC. The developed prognostic model, incorporating immune cell markers, exhibited robust predictive accuracy for patient outcomes, showing significant correlations with immunotherapy responses and drug sensitivities.</p><p><strong>Conclusions: </strong>This study presents a groundbreaking exploration of the OC TME, offering vital insights into its molecular intricacies. By systematically deciphering the TME-associated gene signatures, the research illuminates the potential of these biomarkers in refining patient prognosis and guiding treatment strategies. Our findings underscore the necessity for personalized medicine in OC treatment, potentially enhancing patient survival rates and quality of life. This study marks a significant stride in understanding and combatting the complexities of OC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6182-6200"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-clear cell renal cell carcinoma narrative review: where we are in 2024.","authors":"Michael J Pierro, Alexander Gallan, Deepak Kilari","doi":"10.21037/tcr-24-737","DOIUrl":"10.21037/tcr-24-737","url":null,"abstract":"<p><strong>Background and objective: </strong>Advances in non-clear cell renal cell carcinoma (RCC) have lagged behind clear cell RCC due to the heterogeneity and relative rarity of the disease. However, more advanced molecular and genetic testing has allowed us to gain a more detailed and nuanced appreciation of these malignancies. This has laid the foundation for the identification of the distinct mutational and molecular patterns such as succinate dehydrogenase (SDH)-deficient RCC, fumarate hydratase (FH)-deficient RCC, and translocation RCC, so that clinicians can create a more personalized approach to their clinical management. Particularly for the rare non-papillary RCC variant histologies, clinical trial representation is lacking. In the discussed studies, no histology enrolled more than 29 patients of any particular RCC aside from Papillary. As such, evidence-based management decisions can be challenging to make for this patient population.</p><p><strong>Methods: </strong>We have collected the most up-to-date available evidence to describe the pathophysiology, molecular, and pathologic characteristics of the more commonly seen non-clear cell RCC variants, including papillary, chromophobe, translocation, FH-deficient, as well as a group of \"unclassified\" RCCs. Additionally, we provide an overview of the available evidence from recent clinical trials for non-clear cell RCC and current treatment paradigms.</p><p><strong>Key content and findings: </strong>The diagnostic approach for renal malignancies is rapidly changing, favoring a more molecular and genetically based approach. These techniques will allow for a more detailed understanding of the clinical behavior of these cancers. Most data for non-clear cell RCC are from single-arm phase 2 clinical trials. The clinical response to vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) varies greatly by histology.</p><p><strong>Conclusions: </strong>Molecularly targeted therapy as monotherapy or when combined with immunotherapy have efficacy in non-clear cell RCC, though there are differences in treatment response by histology.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6403-6412"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics decipher the immune microenvironment and unveil therapeutic strategies for postoperative ovarian cancer patients.","authors":"Zhibing Liu, Fei Wang, Weiwei Chen, Yujie Zhai, Jinbo Jian, Xiaole Wang, Yingjiang Xu, Jiajia An, Lei Han","doi":"10.21037/tcr-24-656","DOIUrl":"10.21037/tcr-24-656","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a highly aggressive and often fatal disease that frequently goes undetected until it has already metastasized. The classic treatment for OC involves surgery followed by chemotherapy. However, despite the effectiveness of surgery, relapse is still a common occurrence. Unfortunately, there is currently no ideal predictive model for the progression and drug sensitivity of postoperative OC patients. Cell death patterns play an important role in tumor progression. So we aimed to investigate their potential to be used as indicators of postoperative OC prognosis and drug sensitivity.</p><p><strong>Methods: </strong>A total of 12 programmed cell death (PCD) patterns were employed to construct novel classification and prognosis model. Bulk transcriptome, genomics, and clinical information were collected from The Cancer Genome Atlas (TCGA) Program-OV, GSE9891, GSE26712, GSE49997 and GSE63885. In addition, single-cell transcriptome data GSE210347 were procured from the Gene Expression Omnibus (GEO) database for subsequent analysis.</p><p><strong>Results: </strong>In this study, a novel PCD classification has been employed to phenotype postoperative OC patients, revealing that patients in cluster 1 exhibited heightened sensitivity to immune-based therapies combined with high expression of chemokines, interleukins, interferons, and checkpoints. Meanwhile, a programmed cell death index (PCDI) was established using an 8-gene signature with the help of a machine learning algorithm. The patients with high-PCDI had a worse prognosis after surgery in OC. In addition, we also found that patients with low PCDI patients may exhibit sensitivity to immunotherapy, while those with high PCDI patients may display increased responsiveness to tyrosine kinase inhibitors.</p><p><strong>Conclusions: </strong>This study provides a novel PCD model and nomogram that can effectively predict the clinical prognosis and drug sensitivity of OC patients post-surgery.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6028-6044"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lncRNA signature associated with endoplasmic reticulum stress supports prognostication and prediction of drug resistance in acute myelogenous leukemia.","authors":"Yu Fu, Shupeng Wang, Lingyu Meng, Yahui Liu","doi":"10.21037/tcr-24-722","DOIUrl":"10.21037/tcr-24-722","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute myelogenous leukemia (AML) is a type of blood cancer that is characterized by the accumulation of young and undeveloped myeloid cells in the bone marrow. It is considered a heterogeneous disease due to its diverse nature. Endoplasmic reticulum (ER) stress has emerged as a critical regulator of tumor development and drug resistance in various cancers. Long non-coding RNAs (lncRNAs) have been found to play a role in the development and prognosis of AML. Nonetheless, there is still limited understanding regarding the involvement of ER stress-related lncRNAs in AML prognosis and their predictive ability for drug resistance. The objective of this study was to examine the potential prognostic and predictive significance of an ER stress-related lncRNA signature in patients diagnosed with AML.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Based on the bulk RNA sequence data, we constructed an ER stress-related lncRNA signature using least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. We established nomograms and calibration curves to assess the clinical value of the signature by analyzing overall survival (OS) rates between different risk groups. We also conducted tumor mutation burden (TMB) analysis, predicted immune responses, performed functional and biological enrichment analysis, and evaluated drug sensitivity to investigate the impact of the prognostic signature. Additionally, we built a consensus cluster to explore the need for personalized immunotherapy approaches in treating patients with AML.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A prognostic signature was constructed using 227 ER stress-related lncRNAs that showed differential expression. Patients in the high-risk category demonstrated decreased OS rates in comparison to individuals in the low-risk category. The findings from the nomogram and receiver operating characteristic (ROC) curve analysis suggest a notable disparity in age between the different categories. Among the group at high risk, we noticed a considerably greater TMB in comparison to the low-risk group. Furthermore, individuals with both an elevated risk score and high TMB demonstrated the most unfavorable survival rates. Significant differences were observed in the immune responses between the groups classified as high- and low-risk. We then systematically evaluated three different clusters to assess immune responses and drug responses. Through analyzing the association between the risk score and various medications, we have discovered 18 potential drug contenders capable of effectively addressing AML. Furthermore, we conducted pathway analyses to determine the targeted pathways of these drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our data serve as a valuable resource for decoding the immune responses, somatic mutational landscape, drug resistance, and potential biological functions in AML patients. Additionally, our findings offer valuable insights into the ass","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6165-6181"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of postoperative radiotherapy and definitive radiotherapy for non-metastatic adenoid cystic carcinoma of the head and neck, a propensity score matching based on the SEER database.","authors":"Mingyu Tan, Yanliang Chen, Tianqi Du, Qian Wang, Xun Wu, Xiaohu Wang, Hongtao Luo, Shilong Sun, Qiuning Zhang, Wenzhen Yuan","doi":"10.21037/tcr-24-1221","DOIUrl":"10.21037/tcr-24-1221","url":null,"abstract":"<p><strong>Background: </strong>Treating patients with head and neck adenoid cystic carcinoma (HNACC) presents surgical problems in various scenarios. Limited studies explore definitive radiation's impact on patient survival, with inadequate data correlating it to postoperative radiotherapy. Using the Surveillance, Epidemiology, and End Results (SEER) program, we conducted an objective analysis to evaluate the impact of definitive radiation on the survival of HNACC patients without distant metastases, aiming to uncover its nuanced pros and cons.</p><p><strong>Methods: </strong>This study conducted a comprehensive analysis of individuals diagnosed with HNACC within the SEER database from 2000 to 2023. Disease-specific survival (DSS) and overall survival (OS) were evaluated using diverse statistical methods. Propensity score matching (PSM) reduced covariate variations and selection biases, allowing for comparisons of postoperative and definitive radiotherapy groups.</p><p><strong>Results: </strong>A total of 2,072 patients were encompassed within this study. The postoperative radiotherapy group yielded significant advantages in OS and DSS (P<0.001). In matched cohorts, the 5-year prognostic OS stood at 55% and 37%, respectively, while DSS figures were 65% and 46%, correspondingly. In advanced T4 cases, DSS differences lacked significance (P=0.42). Additionally, the outcomes of OS and DSS were notably influenced by variables such as T-stage, N-stage, tumor stage, and chemotherapy.</p><p><strong>Conclusions: </strong>Surgical intervention remains a pivotal component of comprehensive treatment for patients diagnosed with operable HNACC. Definitive radiation is appropriate for less treatable situations, particularly in local advanced HNACC. Systemic treatment may assist HNACC patients at risk of distant metastases.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"6045-6056"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic signature detects homologous recombination deficient in glioblastoma.","authors":"Dongdong Luo, Aiping Luo, Su Hu, Hailin Zhao, Xuefeng Yao, Dan Li, Biao Peng","doi":"10.21037/tcr-23-2077","DOIUrl":"10.21037/tcr-23-2077","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a frequent malignant tumor in neurosurgery characterized by a high degree of heterogeneity and genetic instability. DNA double-strand breaks generated by homologous recombination deficiency (HRD) are a well-known contributor to genomic instability, which can encourage tumor development. It is unknown, however, whether the molecular characteristics linked with HRD have a predictive role in GBM. The study aims to assess the extent of genomic instability in GBM using HRD score and investigate the prognostic significance of HRD-related molecular features in GBM.</p><p><strong>Methods: </strong>The discovery cohort comprised 567 GBM patients from The Cancer Genome Atlas (TCGA) database. We established HRD scores using the single nucleotide polymorphism (SNP) array data and analyzed transcriptomic data from patients with different HRD scores to identify biomarkers associated with HRD. A prognostic model was built by using HRD-related differentially expressed genes (DEGs) and validated in a distinct cohort from the Chinese Glioma Genome Atlas (CGGA) database.</p><p><strong>Results: </strong>Based on the SNP array data, the gene expression profile data, and the clinical characteristics of GBM patients, we found that patients with a high HRD score had a better prognosis than those with a low HRD score. The DNA damage repair (DDR) signaling pathways were notably enriched in the HRD-positive subgroup. The prognostic model was developed by including HRD-related DEGs that could evaluate the clinical prognosis of patients more efficiently than the HRD score. In addition, patients with a low-risk score had a considerably augmented signature of γδT cells. Finally, through univariate and multivariate Cox regression analyses, it was demonstrated that the prognostic model was superior to other prognostic markers.</p><p><strong>Conclusions: </strong>In conclusion, our research has not only demonstrated that a high HRD score is a valid prognostic biomarker in GBM patients but also built a stable prognosis model [odds ratio (OR) 0.18, 95% confidence interval (CI): 0.11-0.23, P<0.001] that is more accurate than conventional prognostic markers such as O6-methylguanine-DNA methyltransferase (MGMT) methylation (OR 0.55, 95% CI: 0.33-0.91, P=0.02).</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 11","pages":"5883-5897"},"PeriodicalIF":1.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}