Clinical & Translational Oncology最新文献

{"title":"Dysfunctional mismatch repair in patients with early triple-negative breast cancer.","authors":"María Muñiz-Castrillo, Noel Blaya Boluda, Esmeralda García-Torralba, Paula Jiménez-Fonseca, Carmen González Del Rey, Milagros Balbín, Ginés Luengo-Gil, Francisco Ayala de la Peña, Emilio Esteban González, Alberto Carmona-Bayonas","doi":"10.1007/s12094-025-03933-x","DOIUrl":"10.1007/s12094-025-03933-x","url":null,"abstract":"<p><strong>Background: </strong>While mismatch repair (MMR) deficiency is well-characterized in several cancers, its role in triple-negative breast cancer (TNBC) remains unclear. We comprehensively assessed MMR in early-stage TNBC, examining its prevalence, clinical correlations, prognostic value, relationship with microsatellite instability (MSI), and patterns of intratumoral heterogeneity.</p><p><strong>Methods: </strong>Two early-stage TNBC cohorts were investigated for germline mutations using next-generation sequencing, protein expression by immunohistochemistry, and MSI status through molecular detection. Associations with clinicopathological characteristics and survival were examined. Results were validated using The Cancer Genome Atlas (TCGA) data.</p><p><strong>Results: </strong>Among 259 patients, MMR deficiency was observed in 8.2%, all showing PMS2 loss, while 2 germline PMS2 mutations (2.7%) were detected. At the somatic level, 35.8% showed heterogeneous MMR expression, more frequently in earlier stages (IA-IIA 41.4% vs. IIB-III 22.4%, p = 0.04) and smaller tumors (cT1-2 39.1% vs. cT3-4 18.5%, p = 0.01). MMR status showed no significant associations with other clinicopathological variables or survival. No MSI was detected in MMR-deficient cases. The 5-year recurrence rate was 16.0% (95% CI 10.0-24.0) for MMR-intact, 20.0% (95% CI 4.5-43.0) for MMR-deficient, and 17.9% (95% CI 9.8-28.1) for heterogeneous tumors (p = 0.75). Pathological complete response to neoadjuvant chemotherapy was similar across MMR status groups. These findings were consistent with analyses using TCGA data.</p><p><strong>Conclusion: </strong>MMR system shows a low rate of alterations in TNBC, with its deficiency being infrequent and not correlated with MSI. Although MMR system isolated evaluation may not be justified in early-stage TNBC due to its limited clinical impact, its inclusion in multigene panels should be further considered.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3924-3937"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits of a mindfulness and compassion program for cancer patients: experience in a Spanish public hospital setting.","authors":"Marcial Arredondo, Ferran Mestanza, Ruth Carpio, Joan Escarrabill, Clara López-Solà, Eva Palou, Lesly Acosta, Laia Fernández, Vanesa Vilas-Riotorto, Tamara Sauri, Begoña Mellado","doi":"10.1007/s12094-025-03913-1","DOIUrl":"10.1007/s12094-025-03913-1","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness-based interventions have been shown to improve the quality of life of cancer patients and are widely recommended.</p><p><strong>Methods: </strong>This was a non-randomized, single-center study designed to assess the feasibility and benefits of a mindfulness and compassion program for individuals living with cancer (MCP-C). The primary objective was to evaluate the feasibility of the program, while the secondary objective was to assess its effectiveness in adult cancer patients and their relatives. Before and after completing the program, participants completed the 12-item General Health Questionnaire (GHQ- 12) and the Hospital Anxiety and Depression Scale (HADS). A qualitative study was also conducted using focus groups and a structured qualitative survey.</p><p><strong>Results: </strong>A total of eight courses were delivered, six in person in 2019 and two online in 2020. A total of 153 participants were enrolled, of whom 142 were considered evaluable. Among them, 90 (64.3%) completed the program, including 75 patients (83.3%) and 15 relatives. The intervention was associated with significant reductions (p < 0.01) in mean scores on the GHQ- 12 and the HADS-A and HADS-D subscales. In the qualitative assessment, participants reported multiple benefits, including increased awareness of health-related decision-making, improved relationship with the disease, a sense of companionship, emotional support, and overall enhancements in daily life.</p><p><strong>Conclusions: </strong>Implementing an 8-week mindfulness and self-compassion program within the routine practice of a public hospital was feasible and led to significant improvements in the psychological well-being of cancer patients and their relatives.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4040-4050"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006540","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 and recurrence risk predictive values of tumor infiltrating lymphocytes in HER2-low breast cancer.","authors":"Lijun Song, Xiangjun Li, Lulu Wang, Jian Cui, Teng Ma","doi":"10.1007/s12094-025-03921-1","DOIUrl":"10.1007/s12094-025-03921-1","url":null,"abstract":"<p><strong>Background: </strong>With the emergence of novel anti-HER2 antibody drug conjugates, patients with HER2-low breast cancer have received increased attention. Tumor-infiltrating lymphocytes (TILs) are significantly associated with survival benefits in cancers. However, their prognostic value in patients with low her2 breast cancer is unknown. Therefore, we aimed to determine the relationship between TILs and recurrence in patients with HER2-low breast cancer.</p><p><strong>Methods: </strong>Clinicopathological data were retrospectively collected from patients with human epidermal growth factor receptor 2 (HER2) low-expression breast cancer who underwent consultations at Qingdao University Affiliated Hospital. We determined the correlation between TILs and disease-free survival (DFS) followed by the threshold value of TILs using X-tile software. Survival was assessed using Kaplan-Meier analysis, and cox regression analysis was performed for recurrence risk modeling.</p><p><strong>Results: </strong>Our study showed a 15% TIL level was the optimal cutoff for DFS. The low and high TILs survival curves showed significant differences in the log-rank test (p = 0.009). Cox regression analyses found that lymph node stage, histologic grading, TILs, and Ki-67 were independent variables influencing the prognosis (p < 0.05). On this basis, we developed a risk prediction model to accurately predict the 3- and 5-year disease-free survival rates of patients with HER2-low breast cancer, the model demonstrated good overall performance.</p><p><strong>Conclusion: </strong>TILs are associated with recurrence in patients with breast cancer and low HER2 levels. TILs > 0.15 is a reliable indicator of DFS. For patients with low TILs (≤ 0.15), extensive follow-up is required. These findings provide a basis for targeted, individualized treatment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3902-3910"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy may promote the occurrence of radiation-induced brain injury in NSCLC patients with brain metastases undergoing radiotherapy: a retrospective propensity score-matching and inverse probability of treatment weighting study.","authors":"Sai Li, JingYi Tang, Ruiting Chen, Yong Li, Shulin Liu, Xianjing Chu, Lang Li, Weihua Liao","doi":"10.1007/s12094-025-03928-8","DOIUrl":"10.1007/s12094-025-03928-8","url":null,"abstract":"<p><strong>Purpose: </strong>The combination of radiotherapy (RT) and immunotherapy can significantly improve the prognosis of non-small cell lung cancer (NSCLC) patients. However, concerns about whether the synergistic effect may increase the risk of radiation-induced brain injury (RIBI) remain controversial. This study aims to explore the impact of immune checkpoint inhibitors (ICIs) on the occurrence of RIBI in patients with NSCLC brain metastases (BMs).</p><p><strong>Methods: </strong>This study retrospectively enrolled NSCLC patients with BMs undergoing RT between January 2017 and December 2023. Patients were stratified into groups based on PD-1/PD-L1 checkpoint inhibitors, administration, with confounding factors controlled via propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Final cohorts included an RT-only group (n = 54) and an RT + ICIs group (n = 28). RIBI incidence and progression-free survival (PFS) were compared between groups.</p><p><strong>Results: </strong>After 1:1 PSM analysis, the incidence of RIBI in the RT + ICIs group was significantly higher than that in the RT-only group (17.9% vs 42.9%, P = 0.042). Further IPTW analysis showed that the incidence of RIBI in the RT + ICIs group was significantly higher than that in the RT-only group (24.8% vs 47.8%, P = 0.033). Regarding the impact on PFS, there was no statistical difference between the two groups in both PSM and IPTW (P > 0.05).</p><p><strong>Conclusions: </strong>Immunotherapy combined with RT may increase the occurrence of RIBI in patients with NSCLC BMs. The mechanism underlying this phenomenon requires further investigation.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3877-3885"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A topical nociceutical formulation ameliorates chemotherapy-induced peripheral neuropathy: a pilot randomized clinical study.","authors":"Sonia Servitja, Maria Castro-Henriques, Iñaki Álvarez-Busto, Carlota Díez-Franco, Alba Medina-Castillo, Maria Asunción Algarra-García, Elena López-Miranda, Margaret Lario-Martínez, Maria Isabel Luengo-Alcázar, Miguel Borregón, Ana Davó, Anna Gasull-Delgado, Sara Roque-García, Ana Gonzaga-López, Jesús Manuel Poveda-Ferriols, Severine Pascal, Ana María Mitroi-Marinescu, Marta García-Escolano, Asia Fernández-Carvajal, Clotilde Ferrándiz-Huertas, Antonio Ferrer-Montiel","doi":"10.1007/s12094-025-04062-1","DOIUrl":"https://doi.org/10.1007/s12094-025-04062-1","url":null,"abstract":"<p><strong>Background: </strong>Up to 80% of patients undergoing taxanes or platinum-based chemotherapy (CT) develop a peripheral polyneuropathy (CIPN), that affects treatment compliance and quality of life (QoL). CIPN is characterized by a remarkable sensitization of peripheral nociceptive endings. We performed a proof-of-concept, double-blind, randomized, two-arms, multicenter clinical study to evaluate if protecting epidermal nociceptive endings with a topical nociceutical formulation prevented CIPN and augmented QoL during CT.</p><p><strong>Material and methods: </strong>Participants started a daily topical application of the assigned formulation in hands (moisturizing or nociceutical). Upon appearance of neuropathic symptoms in hands or feet, they applied the creams twice daily. Diagnosis and follow-up of CIPN was performed using the CTC AE v5.0 criteria.</p><p><strong>Results: </strong>A cohort of 142 patients treated with taxanes and/or platinum agents were randomly distributed into the arms. Withdrawals were similar in both arms. A lower CIPN incidence in hands was observed in the nociceutical arm (32% vs 13%, p = 0.03), while a similar number of participants developed CIPN in feet (73% vs 67%, p = 0.1). Interestingly, the nociceutical formulation increased the number of CT cycles CIPN free (6 vs 8 cycle, p = 0.009). The Leonard Scale Questionnaire revealed that 60% of patients using the moisturizing cream reported frequently bothersome neuropathic symptoms, compared with only 39% in the nociceutical group (p = 0.0017).</p><p><strong>Conclusion: </strong>Protection of nociceptive epidermal terminals with a topical nociceutical formulation reduced the incidence of CIPN in hands and increased the QoL of patients. These findings provide a solid ground for a confirmatory clinical study.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal incontinence after moderately hypofractionated volumetric modulated arc therapy for prostate cancer: incidence and impact on quality of life.","authors":"Joan Lozano, Nicolas Feltes, Montserrat Colomer, Maria Lizondo, Mamen Carmona, Clara Romero, Yolanda Ribas, Saturio Paredes, Manuel Galdeano, Josep Maria Solé","doi":"10.1007/s12094-025-03926-w","DOIUrl":"10.1007/s12094-025-03926-w","url":null,"abstract":"<p><strong>Purpose: </strong>Fecal incontinence (FI) is a late toxicity consequence in prostate cancer patients treated with current radiotherapy schedules that remains poorly described and understood. The main objective of this work is to describe the incidence of appearance of FI in these patients, and to analyze whether this late radiotoxicity event affects the quality of life of survivors.</p><p><strong>Methods: </strong>Prospective follow-up study was performed on a cohort of 91 patients with non-metastatic prostate cancer undergoing moderately hypofractionated volumetric modulated arc therapy (VMAT at 2.5-3 Gy/session) with image-guided radiotherapy (IGRT) in a real-world clinical practice scenario. The incidence of FI (using the Vaizey score) and FI-free survival time after completion of radiotherapy were presented. We additionally assessed the scores on the FI Quality of Life (FIQL) scale in both patients with and without FI.</p><p><strong>Results: </strong>Within 2 years after radiotherapy, 10 of 91 patients (11%) showed some degree of FI with an average onset at 13.59 months. Patients with some degree of FI had worse FIQL scores than those without FI (p < 0.001).</p><p><strong>Conclusion: </strong>Patients with localized prostate cancer treated with moderately hypofractionated VMAT/IGRT had a significant incidence of fecal incontinence, which negatively affected the quality of life of survivors.</p><p><strong>Trial registry: </strong>The study protocol was registered on clinicaltrials.gov (NCT04262609) on 5 February 2020.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4003-4010"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of CST2 in the pathogenesis and prognosis of esophageal squamous cell carcinoma.","authors":"Flor Esther Garza Martinez, Mitsuro Kanda, Yusuke Sato, Haote Zhu, Tuvshin Bayasgalan, Mohammad Hussain Hamrah, Dai Shimizu, Haruyoshi Tanaka, Shinichi Umeda, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Goro Nakayama, Yasuhiro Kodera","doi":"10.1007/s12094-025-03925-x","DOIUrl":"10.1007/s12094-025-03925-x","url":null,"abstract":"<p><strong>Purpose: </strong>Cystatin SA (CST2) is a cysteine protease inhibitor that is overexpressed in several malignancies; however, its involvement in esophageal squamous cell carcinoma (ESCC) has yet to be investigated. This study evaluates CST2 expression, its association with clinicopathological parameters, and its prognostic significance in ESCC. We further investigate the biological functions of CST2 to assess CST2 impact on tumor progression and its potential as a prognostic marker.</p><p><strong>Methods: </strong>CST2 expression was quantified in 16 ESCC cell lines and 165 paired tumor and adjacent non-cancerous tissues using quantitative reverse-transcription PCR (qRT-PCR). siRNA-mediated CST2 knockdown assays were performed to assess cellular functions in vitro and in vivo. Associations between CST2 expression and clinicopathological features, recurrence patterns, and survival outcomes, including disease-specific survival (DSS) and disease-free survival (DFS), were analyzed using statistical methods.</p><p><strong>Results: </strong>CST2 mRNA levels were significantly elevated in ESCC tissues compared to normal mucosa. Knockdown of CST2 reduced proliferation, migration, and invasion in vitro, while in vivo models demonstrated smaller tumor volumes in CST2 knockdown groups compared to controls. High CST2 expression correlated with worse DSS and DFS. Multivariable analysis confirmed high CST2 expression as an independent prognostic factor for DSS.</p><p><strong>Conclusion: </strong>CST2 plays a critical role in ESCC pathogenesis and progression. Its overexpression is associated with poor clinical outcomes, suggesting CST2 as a potential prognostic biomarker for recurrence and survival in ESCC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3981-3992"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency and predictors of risk of non-medical opioid use among patients with cancer in a specialized outpatient palliative care clinic.","authors":"Juan Luis Torres-Tenor, Eduardo Bruera, Inés Sánchez-Mañas, Teresa Pérez-Manrique, Aránzazu Castellano-Candalija, Alberto Alonso-Babarro","doi":"10.1007/s12094-025-03929-7","DOIUrl":"10.1007/s12094-025-03929-7","url":null,"abstract":"<p><strong>Purpose: </strong>To assess non-medical opioid use (NMOU) risk frequency in outpatients with cancer, compare at-risk vs. non-risk patients, and evaluate the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) against its shortened version (SOAPP-SF).</p><p><strong>Methods: </strong>/patients. This cross-sectional study was conducted in a tertiary hospital's palliative care clinic. Adult patients with advanced cancer and cancer pain using or initiating prescribed opioids were included. Patients self-completed the SOAPP-R and SOAPP-SF during consultations. Additional data were gathered from medical records.</p><p><strong>Results: </strong>A total of 47 patients completed SOAPP-R and SOAPP-SF to assess NMOU risk, with 28% (n = 13) classified as high-risk by both. High-risk patients were younger (p = 0.003), received higher opioid doses (p = 0.026), used more substances (p = 0.018), and were more frequently employed (p = 0.001). SOAPP-SF showed 0.85 specificity, 0.6 sensitivity, 0.85 negative predictive value, and 0.6 positive predictive value compared to SOAPP-R. Both tests agreed on 61.5% of high-risk and 85% of low-risk cases.</p><p><strong>Conclusions: </strong>Among outpatients with advanced cancer, 28% had high NMOU risk, which was associated with younger age, higher opioid doses, greater substance use, and higher employment rates. SOAPP-SF retained most of the predictive power of the SOAPP-R.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"4051-4057"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospital at home for oncologic patients: SEOM-SEHAD consensus on clinical practice.","authors":"Eulalia B Villegas Bruguera, Kevin Molina Mata, Magdalena Fernandez Martinez de Mandojana, Iosune Guillén Blanco, Manuel Sánchez Cánovas","doi":"10.1007/s12094-025-03875-4","DOIUrl":"10.1007/s12094-025-03875-4","url":null,"abstract":"<p><p>The number of oncologic patients and survival rates are increasing worldwide. This fact implies greater comorbidity and complications associated with cancer and oncologic therapies. Many of these complications require hospitalization which constitutes an additional risk factor for the patient, due to the nosocomial burden such as infections, severe functional deficits or depression. Moreover, the increasing number of hospitalizations implies a significant increase in global sanitary costs. Hospital at Home (HaH) is a resource that allows decompensated patient to remain in home, attended and treated by a hospital multidisciplinary team. Furthermore, HaH has been shown to be clearly cost-effective in multiple pathologies compared to conventional hospitalization. A group of experts from the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Hospital at Home (SEHAD) met to discuss a brief update on home complex attention of oncologic patients and agree on aspects relating to the clinical diagnosis, admission criteria and management of different profiles.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3860-3866"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048482","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":"Transcriptome analysis of key genes and pathways associated with cisplatin resistance in oral squamous cell carcinoma Cal27 cells.","authors":"Yu Wang, Qiwei Zhao, Long Ding, Xiayang Liu, Zhuang Li, Xinyue Zhou, Danru Wang, Mengtian Du, Guohua Yang, Mingzhu Yin, Xiaohong Guo","doi":"10.1007/s12094-025-03924-y","DOIUrl":"10.1007/s12094-025-03924-y","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) has a poor postoperative recovery and is prone to drug resistance during long-term chemotherapy, but the molecular mechanism of its resistance has not been fully elucidated.</p><p><strong>Methods: </strong>In the present study, a cisplatin-resistant cell line Cal27R was established and the key genes and pathways associated with drug resistance were explored using bioinformatics analysis and molecular biology experimental techniques.</p><p><strong>Results: </strong>Transcriptome analysis reveals a total of 1927 differentially expressed genes (DEGs). GO and further KEGG analysis revealed the DEGs were primarily concentrated in the tumor necrosis factor (TNF) and the mitogen-activated protein kinase (MAPK) signaling pathway. PPI network analysis identified six genes exhibiting significant interactions. Among these, interrogation of the TCGA database revealed elevated expression levels of TNF, TGFB1, and IL1B in tumors from drug-resistant patients, whereas EGF and FOS expression was significantly downregulated. The level of immune infiltration was positive correlated with the expression of TNF, TGFB1, IL6 and EGF, conversely, negative correlated with that of IL1B. Furthermore, low expression of TNF and FOS, as well as high expression of TGFB1, IL6 and EGF, was associated with poor overall prognosis. Based on the comprehensive analysis above, TNF, TGFB1, and EGF were ultimately selected as target genes to positively regulate the cisplatin resistance of Cal27R cells. Furthermore, we validated the expression of target genes in human tongue carcinoma tissues and paired adjacent normal tissues. Knockout of these genes significantly reduced drug resistance, consistent with our initial hypothesis. Whole-exome sequencing (WES) analysis confirmed the absence of underlying mutations, thereby corroborating the bioinformatics predictions.</p><p><strong>Conclusion: </strong>TNF, TGFB1 and EGF were regarded as the key genes associated with cisplatin resistance and poor prognosis in OSCC. Meanwhile, their related TNF and MAPK pathways were considered as the pivotal signaling pathways. Our results provide a theoretical and experimental basis for potential diagnostic and therapeutic targets to address drug resistance in clinical settings.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3949-3964"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}