Translational Oncology最新文献

{"title":"Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors","authors":"Heng Zheng,&nbsp;Yong Pan","doi":"10.1016/j.tranon.2025.102316","DOIUrl":"10.1016/j.tranon.2025.102316","url":null,"abstract":"<div><div>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract, with c-kit and PDGFRA mutations being the primary causes. However, GIST pathogenesis is not still fully understood. Differential expression analysis, Univariate Cox regression and Kaplan-Meier curves were utilized to screen for up-regulated and prognostically relevant genes. The expression distribution was compared across various demographics and clinical groups. The relationship between gene expression and cytokine pathway activation was assessed via CytoSig. Immune cell infiltration was analyzed using TIMER2.0. Four paired GIST and adjacent normal tissues were collected to validate the expression trend. CCK8 assays and scratch wound healing assays were conducted in GIST-T1 and GIST-882 cells. Results indicated that LARP7 was up-regulated in GISTs at both mRNA and protein levels. This elevated expression was associated with poor prognosis, particularly in GISTs located in the small intestine and those with larger tumor sizes. LARP7 was implicated in the expression of IFN-induced genes and the negative regulation of viral processes. Predictions of cytokine pathways supported these findings, and immune cell infiltration analysis revealed a higher presence of CD8+ <em>T</em> cells in GISTs with high LARP7 expression. The lncRNA (H19 or LINC00665)-miRNA(hsa-miR-138–5p) axis targeted LARP7. Furthermore, LARP7 was elevated in imatinib-resistant GISTs, with some other drugs predicted to aid in therapy. LARP7 knockdown resulted in reduced proliferation and migration of GIST-T1 and GIST-882 cells. Overall, high expression of LARP7 correlates with poor prognosis in GISTs, highlighting its potential as a therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102316"},"PeriodicalIF":5.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaihu Shugan San and Zuogui Yin synergistically improve premature ovarian failure in a rat model via the PI3K/Akt/mTOR pathway","authors":"Fei Zhang ,&nbsp;RuiFang Liu ,&nbsp;ZhenLing Xu ,&nbsp;WenJie Chen ,&nbsp;XiYa Lu ,&nbsp;Yang Wang","doi":"10.1016/j.tranon.2025.102298","DOIUrl":"10.1016/j.tranon.2025.102298","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;premature ovarian failure (POF) is a significant condition characterized by the early loss of ovarian function, often leading to infertility and other health complications. Traditional Chinese Medicine (TCM) formulations, such as Chaihu Shugan San and Zuogui Yin, have been used to address various gynecological disorders. This study aims to evaluate the therapeutic effects of Chaihu Shugan San, Zuogui Yin, and their combination on POI in a rat model and to elucidate the underlying mechanisms involving the PI3K/Akt/mTOR signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, a premature ovarian failure (POF) rat model was established using chronic unpredictable mild stress (CUMS) combined with cyclophosphamide injections. Rats were treated with Chaihu Shugan San, Zuogui Yin, or their combination. Key outcomes, including ovarian granulosa cell proliferation, follicular integrity, and hormonal levels (FSH and E2), were assessed. Histopathological changes in ovarian tissue were evaluated using hematoxylin and eosin (H&amp;E) staining, while apoptosis was detected through immunohistochemistry and Western blot analysis of proteins such as Bcl-2, Bax, Caspase3, and Caspase9. The activity of the PI3K/Akt/mTOR signaling pathway was quantified using Western blot, and statistical significance was determined (&lt;em&gt;P&lt;/em&gt; &lt; 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results showed that all three treatments significantly improved ovarian function in the POF rat model. Compared to the model group, Chaihu Shugan San, Zuogui Yin, and their combination increased granulosa cell proliferation (&lt;em&gt;P&lt;/em&gt; &lt; 0.01), reduced follicular atresia (&lt;em&gt;P&lt;/em&gt; &lt; 0.05), and normalized hormone levels (FSH: reduced by 36.5 %; E2: increased by 42.8 %, &lt;em&gt;P&lt;/em&gt; &lt; 0.05). Histopathological analysis confirmed preserved follicular structure and reduced apoptosis in treated groups. Western blot results revealed enhanced PI3K/Akt/mTOR pathway activity, with upregulated Bcl-2 expression (&lt;em&gt;P&lt;/em&gt; &lt; 0.01), downregulated Bax expression (&lt;em&gt;P&lt;/em&gt; &lt; 0.01), and decreased Caspase3 and Caspase9 levels (&lt;em&gt;P&lt;/em&gt; &lt; 0.05). Additionally, CyclinD2 and P70S6 K expression were significantly increased in treated groups, suggesting enhanced cell cycle progression and protein synthesis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Chaihu Shugan San, Zuogui Yin, and their combination exhibit potential efficacy as treatments for POF in rats by enhancing granulosa cell proliferation, preserving follicular integrity, and inhibiting apoptosis. These therapeutic effects are mediated through the activation of the PI3K/Akt/mTOR signaling pathway and regulation of apoptosis-related proteins. This study highlights the importance of further exploring apoptosis-related pathways to understand the therapeutic mechanisms of these TCM formulations, providing a foundation for new clinical strategies to manage POF and related reproductive health issue","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102298"},"PeriodicalIF":5.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF3 promotes colorectal cancer progression by activating p65/NF-κB signaling pathway and inducing an immunosuppressive microenvironment","authors":"Junfeng Xu ,&nbsp;Na Li ,&nbsp;Hui Xie ,&nbsp;Changwei Duan ,&nbsp;Xingchen Liao ,&nbsp;Ruoran Li ,&nbsp;Heng Zhang ,&nbsp;Yuanming Pan ,&nbsp;Xianzong Ma ,&nbsp;Shuwen Du ,&nbsp;Jianqiu Sheng ,&nbsp;Xin Wang ,&nbsp;Lang Yang ,&nbsp;Peng Jin","doi":"10.1016/j.tranon.2025.102310","DOIUrl":"10.1016/j.tranon.2025.102310","url":null,"abstract":"<div><h3>Background</h3><div>Colony-stimulating factor 3 (CSF3) is a cytokine that promotes inflammation by stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. However, the functional importance of CSF3 in colorectal cancer (CRC) remains unclear.</div></div><div><h3>Methods</h3><div>CSF3 expression levels in CRC cells and tissues were detected by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC). <em>In vitro</em> and <em>in vivo</em> assays were performed to investigate the oncogenic function of CSF3 in the tumor associated malignant phenotypes and the tumorigenic capability of CRC cells. Immunocoprecipitation was performed to verify the regulatory effects of CSF3 on IκBα ubiquitination.</div></div><div><h3>Results</h3><div>We found that CSF3 was overexpressed in CRC tissues compared to adjacent normal tissues, which correlated with poor patient survival. <em>In vitro</em>, silencing CSF3 significantly impaired cell proliferation, colony formation, and migration, while enhancing apoptosis. <em>In vivo</em>, silencing CSF3 resulted in reduced tumor growth, weight, and volume, indicating its potential as a therapeutic target. Mechanistically, CSF3 was found to mediate CRC development by activating the NF-κB signaling pathway, as evidenced by the decreased phosphorylation of p65 and reduced IκBα ubiquitination in CSF3-silenced cells. Furthermore, CSF3 silencing modulated immune infiltration in CRC, promoting an anti-tumor immune response and altering the tumor microenvironment.</div></div><div><h3>Conclusion</h3><div>CSF3 modulated the NF-κB signaling pathway through a distinct mechanism involving p65 phosphorylation and the activation of NF-κB by enhancing IκBα ubiquitination, thereby effectively promoting CRC development, and CSF3 may serve as a potential therapeutic target for repressing CRC advance and metastasis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102310"},"PeriodicalIF":5.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis conferred by molecular features of appendix-derived Pseudomyxoma Peritonei","authors":"Ruiqing Ma ,&nbsp;Guojun Li ,&nbsp;Yingjiang Ye ,&nbsp;Lei Liang ,&nbsp;Chong Wang ,&nbsp;Haipeng Zhou ,&nbsp;Pu Zhang ,&nbsp;Lubiao An ,&nbsp;Guanjun Shi ,&nbsp;Qian Chen ,&nbsp;Hongbin Xu ,&nbsp;Zhidong Gao","doi":"10.1016/j.tranon.2025.102279","DOIUrl":"10.1016/j.tranon.2025.102279","url":null,"abstract":"<div><h3>Introduction</h3><div>Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. <em>MUC16</em>-mutated patients had worse PFS (<em>P</em> = 0.016) and OS (<em>P</em> = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) &gt; 1(<em>P</em> = 0.026) or alterations in <em>TP53</em> (<em>P</em> = 0.006) or <em>SMAD4</em> (<em>P</em> = 0.013) had significantly worse OS compared to those with a TMB &lt; 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (<em>P</em> = 0.003) or alterations in <em>TGFBR2</em> (<em>P</em> = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (<em>P</em> = 0.020), <em>TP53</em> (<em>P</em> = 0.004), and <em>MUC16</em> (<em>P</em> = 0.013) were identified as independent prognostic factors for OS, while HRD status (<em>P</em> = 0.003) was independent predictors for PFS in PMP.</div></div><div><h3>Conclusions</h3><div>The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102279"},"PeriodicalIF":5.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPC25 upregulates CCND1 to promote the progression of esophageal squamous cell carcinoma by inhibiting MDM2-mediated E2F1 ubiquitination","authors":"Haoyao Jiang ,&nbsp;Xiangfeng Jin ,&nbsp;Haiyong Gu ,&nbsp;Bin Li ,&nbsp;Zhigang Li ,&nbsp;Yifeng Sun","doi":"10.1016/j.tranon.2025.102300","DOIUrl":"10.1016/j.tranon.2025.102300","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) is highly malignant worldwide. Despite significant advances in the treatment of ESCC, the prognosis remains unfavourable, necessitating research into its mechanisms and treatments. Spindle component 25 (SPC25) can ensure the fidelity of mitotic progression and the accurate segregation of chromosomes, thus plays an important role in the development of malignant tumors, but its role in ESCC is yet to be determined. In this study, the expression of SPC25 was assessed by IHC in 88 primary ESCC samples, with its expression being correlated with advanced clinical features. The function of SPC25 in the proliferation, migration and tumorigenicity of ESCC cells was verified in vitro and in vivo. Mechanistically, SPC25 facilitated tumorigenesis through promoting CCND1 expression. As the transcription factor for CCND1, E2F1 is stabilized by SPC25 through binding the ubiquitin ligase MDM2, resulting in enhanced E2F1 expression, which in turn promotes the expression of CCND1. In addition, overexpression of CCND1 counteracted the effects of SPC25 silencing. Collectively, we demonstrated that the aberrant expression of SPC25 inhibited E2F1 ubiquitination and promoted CCND1 expression, thus accelerating the progression of ESCC. These findings propose novel insights into the role of SPC25 in ESCC and provide potential therapeutic strategies for targeting SPC25 in ESCC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102300"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular effects of clinically relevant chemotherapeutic agents on choline phospholipid metabolism in triple negative breast cancer cells","authors":"Caitlin M. Tressler ,&nbsp;Kanchan Sonkar ,&nbsp;Menglin Cheng ,&nbsp;Vinay Ayyappan ,&nbsp;Ruoqing Cai ,&nbsp;Kristine Glunde","doi":"10.1016/j.tranon.2025.102311","DOIUrl":"10.1016/j.tranon.2025.102311","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype, leading to poor patient outcomes despite aggressive treatment with surgery, radiation, and chemotherapy. There are currently no clinical tests available which measure early on whether TNBC patients respond to the selected chemotherapy treatment regimen. The magnetic resonance spectroscopy (MRS)-detected total choline (tCho) signal was shown to be a promising biomarker for assessing the response to chemotherapy treatment early on, as breast tumor tCho decreases after the first treatment cycle in patients who respond to chemotherapy cocktails. We sought to further investigate these clinical observations at the molecular level by combining metabolic and transcriptomic studies in two human TNBC cell lines treated with six different chemotherapeutic agents. Overall, our findings show that the glycerophosphocholine-to-phosphocholine ratio (GPC/PC) was a more sensitive and more broadly applicable measure of TNBC response to various chemotherapeutic agents than tCho. Specific chemotherapeutic drugs, including 5-fluorouracil and melphalan, resulted in the most significant effects on choline phospholipid metabolism, while other drugs did not significantly alter choline phospholipid metabolism. Overall, several of the six tested chemotherapeutic drugs mainly affected the expression levels of phosphatidylcholine (PtdC)-specific phospholipases and lysophospholipases, leading to the observed GPC/PC and tCho changes following treatment with the chemotherapeutic agents that altered choline phospholipid metabolism. The presented metabolic and transcriptomic findings support that the GPC/PC ratio and PtdC-phospholipases and -lysophospholipases could be further developed for assessing the response to chemotherapy treatment in TNBC patients.</div><div>Statement of Significance: We show that the glycerophosphocholine-to-phosphocholine ratio and phosphatidylcholine-specific-phospholipases and -lysophospholipases are reliable markers for assessing the response to several chemotherapeutic agents, which could help with selecting correct treatments for TNBC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102311"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Currents status of radiotracers for breast cancer imaging in PET","authors":"Chloé Jean ,&nbsp;Stéphane Roux ,&nbsp;Abdelilah Aziz ,&nbsp;Maxence Mocquery-corre ,&nbsp;Rana Bazzi ,&nbsp;Yacine Merrouche ,&nbsp;Stéphane Dedieu ,&nbsp;Nicolas Etique ,&nbsp;Dimitri Papathanassiou ,&nbsp;Jérôme Devy","doi":"10.1016/j.tranon.2025.102304","DOIUrl":"10.1016/j.tranon.2025.102304","url":null,"abstract":"<div><div>Radiolabeled molecules have become valuable tools in the diagnosis, monitoring, and treatment of cancer, particularly breast cancer. Through the use of radiotracers, clinicians can target specific tumor cells, assess microenvironments, and identify metastases. These radiopharmaceuticals, based on radionuclides, enable both imaging and therapeutic applications, leading to personalized cancer treatment. Techniques such as PET, SPECT, and the use of nanoparticles for theranostics are at the forefront of innovation, offering improved precision in both diagnosis and therapy. This review explores the various ways in which radiotracers are leveraged in modern oncology, with a focus on breast cancer, and highlights recent advancements in targeted radionuclide therapy and nanoparticle-based applications.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102304"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant phyllodes tumors with sarcomatous components: A histopathologic and molecular study","authors":"Ting Lei ,&nbsp;Yunjie Song ,&nbsp;Zhiyi Shen ,&nbsp;Yongqiang Shi ,&nbsp;Cunyan Xia ,&nbsp;Xu Deng ,&nbsp;Wenyue Da ,&nbsp;Yan Peng ,&nbsp;Qing Li","doi":"10.1016/j.tranon.2025.102318","DOIUrl":"10.1016/j.tranon.2025.102318","url":null,"abstract":"<div><h3>Background</h3><div>Malignant phyllodes tumors (MPTs) with sarcomatous components are often associated with substantial risks for local and distant recurrences. A more comprehensive characterization of their clinicopathological features and molecular profiles may offer significant potential innovative therapeutic strategies.</div></div><div><h3>Methods</h3><div>A total of ten cases were collected with eight cases undergoing DNA next-generation sequencing (NGS). The clinicopathological characteristics, prognostic information, and genomic profiles were compared to those of MPTs without sarcomatous components.</div></div><div><h3>Results</h3><div>Compared to MPT without sarcomatous components, no significant differences were found in age, tumor position, tumor size, menopausal status, or presence of fibroadenoma (<em>p</em> &gt; 0.05). MPTs with osteosarcoma components had a poor prognosis either compared with other sarcomatous components (<em>p</em> = 0.027) or MPTs without sarcomatous components (<em>p</em> = 0.033). A notably high frequency of mutations was observed in several key genes within MPTs exhibiting sarcomatous components: <em>TP53</em> (<em>n</em> = 6, 75.0 %), <em>MUC16</em> (<em>n</em> = 4, 50.0 %), <em>PTCH1</em> (<em>n</em> = 3, 37.5 %), and <em>APC</em> (<em>n</em> = 3, 37.5 %). In MPTs characterized by sarcomatous components, <em>MCL1</em> (<em>n</em> = 6, 75.0 %) and <em>MYC</em> (<em>n</em> = 5, 62.5 %) demonstrated a notably high frequency of amplification. The NOTCH signaling pathway was significantly associated with MPTs characterized by sarcomatous components (13.6 % vs 75.0 %, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The presence of an osteosarcoma component may serve as an indicator for unfavorable prognosis. Activating mutations in <em>TP53</em> have been identified in these tumors. Furthermore, it typically facilitates tumor formation and progression via the NOTCH signaling pathway. These findings may offer valuable insights for clinical prognosis and identify potential therapeutic targets.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102318"},"PeriodicalIF":5.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic and machine learning analysis of mitochondrial RNA modification genes in lung adenocarcinoma for prognostic and therapeutic implications","authors":"Xiao Zhang ,&nbsp;Jiatao Liu ,&nbsp;Yaolin Cao ,&nbsp;Wei Wang,&nbsp;Haoran Lin,&nbsp;Yue Yu","doi":"10.1016/j.tranon.2025.102306","DOIUrl":"10.1016/j.tranon.2025.102306","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related deaths, driven by complex pathogenesis and poor prognosis. Recognizing the pivotal role of mitochondrial RNA modifications (MRM) in cancer progression, this study aims to provide a comprehensive analysis of MRM-related genes and their clinical relevance in lung adenocarcinoma (LUAD). Integrating multi-omic datasets, we systematically explored the molecular features of MRM-related genes across various cancers and identified distinct expression patterns and prognostic associations. Single-cell analysis further reveals MRM-driven cell-cell interactions and pathway activation, particularly in cycling and epithelial cells. Using advanced machine learning techniques, we developed a novel prognostic signature—the Mitochondrial RNA Modification-related Signature (MRMS)—comprising nine genes: TXN, LDHA, HMGA1, SFTPB, KRT8, ALG3, S100A16, HSPD1, and ALDOA. The MRMS demonstrates superior predictive performance for LUAD survival compared to previously reported models. Our findings uniquely link MRMS to increased tumor mutational burden, genetic instability, and an immunosuppressive tumor microenvironment characterized by reduced immune cell infiltration and elevated tumor purity. Additionally, MRMS is associated with immunotherapy-related features, suggesting its potential in predicting treatment response. Experimental validation identified ALG3 as an oncogenic driver in LUAD, influencing tumor cell proliferation, migration, and invasion. In conclusion, this study establishes MRMS as a robust prognostic biomarker and highlights its dual role in shaping the tumor immune microenvironment and guiding therapeutic strategies. These findings provide novel insights into mitochondrial RNA modifications and their potential applications in personalized treatment for LUAD.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102306"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 prognosis for T4b rectal cancer with different pelvic compartment involvement treated using neoadjuvant chemoradiotherapy and implications for refinement of the current T staging system: A retrospective cohort study","authors":"Yang-zi Zhang ,&nbsp;Maxiaowei Song ,&nbsp;Shuai Li ,&nbsp;Jian Tie ,&nbsp;Xiang-gao Zhu ,&nbsp;Yong-heng Li ,&nbsp;Ai-wen Wu ,&nbsp;Yong Cai ,&nbsp;Wei-hu Wang","doi":"10.1016/j.tranon.2025.102313","DOIUrl":"10.1016/j.tranon.2025.102313","url":null,"abstract":"<div><h3>Purpose</h3><div>Although classified as one stage, T4b rectal cancer actually represents a group of heterogeneous diseases. Our study aimed to assess the prognosis difference of T4b rectal cancer involving inferior pelvic and other pelvic compartments. This information may be helpful in refinement of the current T staging system.</div></div><div><h3>Methods</h3><div>We retrospectively analysed data from 195 patients with magnetic resonance imaging-identified locally advanced T4b rectal cancer who received neoadjuvant chemoradiotherapy between January 2010 and December 2019. 104 patients had only inferior pelvic compartment involvement (group A) while 91 patients had anterior, posterior or lateral pelvic compartment involvement (group B). Short-term and long-term outcomes were compared between the two groups.</div></div><div><h3>Results</h3><div>After neoadjuvant therapy, 80.8 % patients (84/104) in group A and 92.3 % patients (84/91) in group B underwent surgery. The R0 resection rates were 97.6 % and 89.3 %, respectively. 8.7 % patients (9/104) in group A achieved clinical complete response and adopted watch-and-wait strategy. Patients in group A had significantly superior 5-year progression-free survival (PFS) (67.8 % vs. 55.5 %, <em>P</em> = 0.032) and overall survival (OS) (89.6 % vs. 71.8 %, <em>P</em> = 0.001) than group B. Multivariable Cox regression analysis also identified pelvic compartment involvement classification as an independent predictor of PFS (hazard ratio 1.776, <em>P</em> = 0.046) and OS (hazard ratio 3.477, <em>P</em> = 0.004).</div></div><div><h3>Conclusion</h3><div>T4b rectal cancers with involvement limited to the inferior pelvic compartment had superior prognosis compared to those involving other pelvic compartments. These differences should be investigated further and taken into consideration in refinement of the current T staging system.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"53 ","pages":"Article 102313"},"PeriodicalIF":5.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}