Yu Peng, Nan Jia, Jingyu Wang, Shilei Dong, Shujun Li, Wei Qin, Hongyun Shi, Kuan Liu
{"title":"Analysis of Multiple Programmed Cell Death Patterns and Functional Validations of Apoptosis-Associated Genes in Lung Adenocarcinoma.","authors":"Yu Peng, Nan Jia, Jingyu Wang, Shilei Dong, Shujun Li, Wei Qin, Hongyun Shi, Kuan Liu","doi":"10.1245/s10434-025-17224-w","DOIUrl":"https://doi.org/10.1245/s10434-025-17224-w","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is marked by its considerable aggressiveness and pronounced heterogeneity. Programmed cell death (PCD) plays a pivotal role in the progression of tumors, their aggressive behavior, resistance to treatment, and recurrence of the disease.</p><p><strong>Patients and methods: </strong>Using expression data from 878 patients across four multicenter cohorts, we identified 13 consensus prognostic genes from 1481 genes associated with PCD. We employed 10 machine-learning algorithms, generating 101 combinations, from which the optimal algorithm was chosen to develop an artificial intelligence-derived cell death index (CDI) on the basis of the average C-index.</p><p><strong>Results: </strong>The training cohort and three external validation cohorts consistently demonstrated that CDI could accurately predict LUAD prognosis. Moreover, CDI showed significantly greater accuracy than traditional clinical variables, molecular characteristics, and 22 previously published signatures. Patients in the low-CDI group had a more favorable prognosis, higher levels of immune cell infiltration, better responsiveness to immunotherapy, and a higher likelihood of displaying the \"hot tumor\" phenotype. Single-cell analysis revealed that neutrophils had the highest CDI scores and exhibited significant differences in marker gene expression.</p><p><strong>Conclusions: </strong>Pseudotime trajectory analysis indicated that BCL2L14 plays a crucial role in the developmental pathway of neutrophils, potentially influencing the fate of LUAD cells. Knockdown of BCL2L14 significantly reduced the growth, proliferation, and colony formation abilities of LUAD cells, while also enhancing apoptosis rates.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianlin Lai, Haoxiang Zhang, Long Huang, Yifeng Tian, Shi Chen
{"title":"Fluorescence Laparoscopic Local Resection of Pancreatic Head Tumor with End-to-End Pancreatic Anastomosis: A New Surgical Strategy for Pancreatic Head Tumor Resection.","authors":"Jianlin Lai, Haoxiang Zhang, Long Huang, Yifeng Tian, Shi Chen","doi":"10.1245/s10434-025-17246-4","DOIUrl":"https://doi.org/10.1245/s10434-025-17246-4","url":null,"abstract":"<p><strong>Background: </strong>With the application of new technologies such as three-dimensional and fluorescent staining, laparoscopic surgery is more comprehensive, accurate, and safe.<sup>1-3</sup> For specific borderline or benign pancreatic head tumors that are small, well-differentiated, and have an intact capsule, laparoscopic local enucleation of the pancreatic head tumor is the preferred surgical approach;<sup>4,5</sup> however, when the tumor involves the pancreatic duct, it is often necessary to resect the pancreatic duct and reconstruct it. This paper introduces a local resection of the pancreatic head tumor with end-to-end anastomosis of the pancreatic duct under fluorescence laparoscopy. According to literature review, there are no reports regarding end-to-end anastomosis of the pancreatic head duct under laparoscopy. PATIENT AND METHODS: Using magnetic resonance imaging (MRI) examination, a 35-year-old female was found to have a solid pseudopapillary neoplasm in the pancreatic head sized 5.4 × 3.8 × 4.2 cm. We performed fluorescence laparoscopic local resection of the pancreatic head tumor. During the operation, the tumor involved the main pancreatic duct, and Takada's end-to-end anastomosis of the pancreatic duct was performed.</p><p><strong>Results: </strong>The duration of the operation was 180 min and blood loss was 100 mL. The patient recovered smoothly and was discharged on the eighth day after operation. Postoperative pathology suggested a solid pseudopapillary neoplasm. There was no dilation of the pancreatic duct 3 months after surgery.</p><p><strong>Conclusion: </strong>Laparoscopic local tumor enucleation has been widely accepted in the treatment of small, well-encapsulated, well-differentiated benign tumors of the pancreatic head. When the pancreatic head tumor involves the main pancreatic duct, Takada's end-to-end anastomosis of the pancreatic duct provides a new surgical strategy.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren M Perry, Varadan Sevilimedu, Natalia Polidorio, Nour Abuhadra, Monica Morrow, George Plitas, Stephanie Downs-Canner
{"title":"ASO Visual Abstract: Predictors of Pathologic Complete Response with Neoadjuvant Chemo-Immunotherapy in Early-Stage Triple-Negative Breast Cancer.","authors":"Lauren M Perry, Varadan Sevilimedu, Natalia Polidorio, Nour Abuhadra, Monica Morrow, George Plitas, Stephanie Downs-Canner","doi":"10.1245/s10434-025-17248-2","DOIUrl":"https://doi.org/10.1245/s10434-025-17248-2","url":null,"abstract":"","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and Biological Significance of Sodium Channel Modifier 1 as a Component of the Minor Spliceosome in Hepatocellular Carcinoma.","authors":"Takashi Ofuchi, Hajime Otsu, Kiyotaka Hosoda, Tomohiko Ikehara, Satoshi Higuchi, Takanari Tatsumi, Kazuki Omachi, Akinori Tsujimoto, Kosuke Hirose, Yasuo Tsuda, Yusuke Yonemura, Hiromitsu Hayashi, Takaaki Masuda, Masaaki Iwatsuki, Koshi Mimori","doi":"10.1245/s10434-025-17108-z","DOIUrl":"https://doi.org/10.1245/s10434-025-17108-z","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. The progression of HCC involves complex molecular mechanisms, including chromosomal amplification and alterations in pre-mRNA splicing. In this study, we investigated sodium channel modifier 1 (SCNM1), a component of the minor spliceosome, as a potential oncogenic driver of HCC.</p><p><strong>Methods: </strong>We analyzed SCNM1 expression and its relationship with clinical outcomes using The Cancer Genome Atlas and GSE14520 datasets and patient samples. Functional assays, including realtime-quantitative polymerase chain reaction, Western blotting, colony formation, and apoptosis analyses, were performed to elucidate the role of SCNM1 in HCC progression. We also evaluated the correlations between SCNM1 and its downstream targets DERL2 and BAG6.</p><p><strong>Results: </strong>Because of DNA copy number gain and arm-level amplification of chromosome 1q, SCNM1 expression was significantly elevated in HCC tissues. High SCNM1 expression correlated with poor prognosis and was identified as an independent prognostic factor. Via its splicing activity, SCNM1 promotes tumor growth, suppresses apoptosis, and regulates the expressions of DERL2 and BAG6, which contribute to cancer cell survival by facilitating protein degradation and suppressing apoptosis. Overexpression of SCNM1 is observed in multiple cancer types, suggesting a broad oncogenic role.</p><p><strong>Conclusions: </strong>Sodium channel modifier 1 plays a critical role in HCC progression by regulating the key pathways involved in tumor proliferation and survival. Its restricted expression in specific cancer types and influence on the minor spliceosome highlights its potential as a cancer-specific therapeutic target. Further research on SCNM1-targeted therapies may provide innovative strategies for treating HCC and other cancers.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of Intratumoral and Peritumoral Deep Learning, Radiomics, and Fusion Models for Predicting KRAS Gene Mutations in Rectal Cancer Based on Endorectal Ultrasound Imaging.","authors":"Yajiao Gan, Qiping Hu, Qingling Shen, Peng Lin, Qingfu Qian, Minling Zhuo, Ensheng Xue, Zhikui Chen","doi":"10.1245/s10434-024-16697-5","DOIUrl":"10.1245/s10434-024-16697-5","url":null,"abstract":"<p><strong>Main objectives: </strong>We aimed at comparing intratumoral and peritumoral deep learning, radiomics, and fusion models in predicting KRAS mutations in rectal cancer using endorectal ultrasound imaging.</p><p><strong>Methods: </strong>This study included 304 patients with rectal cancer from Fujian Medical University Union Hospital. The patients were randomly divided into a training group (213 patients) and a test group (91 patients) at a 7:3 ratio. Radiomics and deep learning models were established using primary tumor and peritumoral images. In the optimally performing regions-of-interest, two fusion strategies, a feature-based and a decision-based model, were employed to build the fusion models. The Shapley additive explanation (SHAP) method was used to evaluate the significance of features in the optimal radiomics, deep learning, and fusion models. The performance of each model was assessed using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA).</p><p><strong>Results: </strong>In the test cohort, both the radiomics and deep learning models exhibited optimal performance with a 10-pixel patch extension, yielding AUC values of 0.824 and 0.856, respectively. The feature-based DLRexpand10_FB model attained the highest AUC (0.896) across all study sets. In addition, the DLRexpand10_FB model demonstrated excellent sensitivity, specificity, and DCA. SHAP analysis underscored the deep learning feature (DL_1) as the most significant factor in the hybrid model.</p><p><strong>Conclusion: </strong>The feature-based fusion model DLRexpand10_FB can be employed to predict KRAS gene mutations based on pretreatment endorectal ultrasound images of rectal cancer. The integration of peritumoral regions enhanced the predictive performance of both the radiomics and deep learning models.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":"3019-3030"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reyhan Tahtasakal, Zuhal Hamurcu, Abdullah Bahadir Oz, Mustafa Balli, Halime Dana, Mustafa Gok, Venhar Cinar, Mevlude Inanc, Elif Funda Sener
{"title":"miR-484 as an \"OncomiR\" in Breast Cancer Promotes Tumorigenesis by Suppressing Apoptosis Genes.","authors":"Reyhan Tahtasakal, Zuhal Hamurcu, Abdullah Bahadir Oz, Mustafa Balli, Halime Dana, Mustafa Gok, Venhar Cinar, Mevlude Inanc, Elif Funda Sener","doi":"10.1245/s10434-024-16656-0","DOIUrl":"10.1245/s10434-024-16656-0","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) is one of the most common causes of death among females. Cancer cells escape from apoptosis, causing the cells to proliferate uncontrollably. MicroRNAs (miRNAs) are known to regulate apoptosis in cancer cells.</p><p><strong>Objective: </strong>This study aimed to determine the change in miR-484 in different BC cells and its relationship with the apoptosis pathway.</p><p><strong>Methods: </strong>In the study, tumor and healthy tissue samples adjacent to the tumor were collected from 42 patients (6 benign, 36 malignant). Tissue samples were classified according to tumor type, tumor histological grade, proliferation index, and molecular subtypes. Gene expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and protein levels were determined using the Western Blot method. The results were analyzed using the delta-delta Ct method.</p><p><strong>Results: </strong>Findings showed that miR-484 expression levels were higher in malignant tumors than in benign tumors, and higher in tumor tissues than healthy tissues. Additionally, it was determined that as Ki-67 levels and histological grade and aggressiveness increased, miR-484 expression levels also increased. In tumor tissue compared with healthy adjacent tissue, there was an increase in BCL2 expression and a decrease in Casp3 and Casp9 expression. Therefore, a positive correlation was found between miR-484 expression and BCL2, and a negative correlation was found between CASP3 and CASP9 expression.</p><p><strong>Conclusion: </strong>Our results show that miR-484 may play a roll as an onco-miR in BC. Increased miR-484 and BCL2, and decreased Casp3, in breast tumor tissues suggest that Casp9 expression may increase uncontrolled cell proliferation by suppressing apoptosis in BC cells and may contribute to tumor progression.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":"2994-3008"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Li, Samuel S K Lam, Yonglin Gao, Emily Shore, David W Anderson, Tomas Hode, Robert C Martin
{"title":"Enhancing the Immunotherapeutic Effect by IP-001 and Irreversible Electroporation in Mouse Oligometastatic Models of Pancreatic Adenocarcinoma.","authors":"Yan Li, Samuel S K Lam, Yonglin Gao, Emily Shore, David W Anderson, Tomas Hode, Robert C Martin","doi":"10.1245/s10434-024-16742-3","DOIUrl":"10.1245/s10434-024-16742-3","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the immunotherapeutic effect of irreversible electroporation (IRE) and IP-001 in pancreatic adenocarcinoma with metastasis.</p><p><strong>Methods: </strong>Orthotopic models of pancreatic adenocarcinoma with hepatic oligometastasis were established by implantation of tumor tissues (derived from Pan02 or KPC cells) size 2 mm<sup>3</sup> into the pancreas and left liver lobe in C57BL/6J mice. One week after implantation, the tumor-burden mice were subjected to saline control, IRE, IP-001, and IRE+IP-001. For IRE therapy (1000 V, 0.1 ms, 10 pulses administered 10 times), the pancreas tumor was treated, whereas the oligometastasis was untreated as the IRE off-target tumor. Intratumoral administration of IP-001(0.4 ml/kg) was performed.</p><p><strong>Results: </strong>In the KPC oligometastatic model, IRE+IP-001 therapy significantly suppressed the growth of oligometastatic tumor. Flow cytometry showed significantly increased tumor-infiltrating lymphocytes (TILs) (e.g., CD8<sup>+</sup> cytotoxic T lymphocytes) and significantly increased monocytes/macrophages in the oligometastatic tumor tissues from IRE+IP-001 treatment compared with the sham control. Significantly decreased Treg cells and tumor-associated macrophages (TAMs) also were found in the oligometastatic tumor tissues from IRE+IP-001 treatment compared with the sham control. In the Pan02 oligometastatic model, both IRE+IP-001 therapy and IRE+anti-PD-L1 immunotherapy significantly suppressed the growth of oligometastatic tumor, which was associated with the increased CD8<sup>+</sup> cytotoxic T lymphocytes. However, increased monocytes/macrophages were found in the mice that had IRE+IP-001 therapy, but not in the mice that had IRE+anti-PD-L1 immunotherapy.</p><p><strong>Conclusion: </strong>The study provided compelling evidence for the efficacy of IRE&IP-001 therapy in suppressing pancreatic tumors, including off-target oligometastatic lesions. The observed off-target effect underscores the importance of systemic immune activation in achieving effective tumor control.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":"2786-2798"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nolan M Winicki, Shannon N Radomski, Yusuf Ciftci, Fabian M Johnston, Jonathan B Greer
{"title":"Predicting Postoperative Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Splenectomy.","authors":"Nolan M Winicki, Shannon N Radomski, Yusuf Ciftci, Fabian M Johnston, Jonathan B Greer","doi":"10.1245/s10434-024-16728-1","DOIUrl":"10.1245/s10434-024-16728-1","url":null,"abstract":"<p><strong>Background: </strong>Hematologic changes after splenectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) can complicate postoperative assessment of infection. This study aimed to develop a machine-learning model to predict postoperative infection after cytoreductive surgery (CRS) and HIPEC with splenectomy.</p><p><strong>Methods: </strong>The study enrolled patients in the national TriNetX database and at the Johns Hopkins Hospital (JHH) who underwent splenectomy during CRS/HIPEC from 2010 to 2024. Demographics, comorbidities, vital signs, daily laboratory values, and documented infections were collected. The patients were divided into infected and non-infected cohorts within 14 days postoperatively. Extreme gradient boost (XGBoost) machine-learning was used to predict postoperative infection. An initial model was generated using the TriNetX dataset and externally validated in the JHH cohort.</p><p><strong>Results: </strong>From TriNetX, 1016 patients were included: 802 in the non-infected group (79%) and 214 (21%) in the postoperative infection group. The mean age was 61 ± 13 years, and 597 (56%) of the patientswere female. Most of the patients underwent CRS/HIPEC with splenectomy for appendiceal cancer (n = 590, 56%), followed by colorectal malignancy (n = 299, 29%). The remainder (n = 127, 15%) underwent CRS/HIPEC with splenectomy for gastric, pancreatic, ovarian, and small bowel malignancies or peritoneal mesothelioma. In detecting any infection, XGBoost exhibited excellent prediction accuracy (area under the receiver operating characteristic curve [AUC], 0.910 ± 0.073; F1 score, 0.915 ± 0.040) and retained high accuracy upon external validation with 96 demographically similar JHH patients (AUC, 0.823 ± 0.08; F1 score, 0.864 ± 0.03).</p><p><strong>Conclusion: </strong>A novel machine-learning algorithm was developed to predict postoperative infection after CRS/HIPEC with splenectomy that could aid in the early diagnosis and initiation of treatment.</p>","PeriodicalId":8229,"journal":{"name":"Annals of Surgical Oncology","volume":" ","pages":"2903-2911"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}