Pathology, research and practice最新文献

{"title":"PESI-MS combined with AI to build a prediction model for lymph node metastasis of papillary thyroid cancer","authors":"Qixin Huang ,&nbsp;Zhenhe Chen ,&nbsp;Lingyu Zhao ,&nbsp;Lichao Jiang ,&nbsp;Ye Wang ,&nbsp;Qianqian Feng ,&nbsp;Yajuan Lei ,&nbsp;Xiaodong Li ,&nbsp;Dingrong Zhong","doi":"10.1016/j.prp.2025.155952","DOIUrl":"10.1016/j.prp.2025.155952","url":null,"abstract":"<div><h3>Objective</h3><div>Construct a prediction model for lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) using Probe Electrospray Ionization Mass Spectrometry (PESI - MS) combined with artificial intelligence (AI), to assist in the preoperative prediction of lymph node metastasis in thyroid carcinoma by intraoperative frozen pathology.</div></div><div><h3>Methods</h3><div>A total of 78 fresh tissue samples of PTC and their adjacent normal tissues were collected. After proper processing, these samples were subjected to detection and analysis using PESI - MS. Subsequently, a classification prediction model was established based on the mass spectrometry test results integrated with AI algorithms. Support vector machine (SVM), random forest (RF), multi - layer perceptron (MLP), and Gradient boosting classifier (GBC) were employed for model building. Employing Support Vector Machine (SVM), Random Forest (RF), and Multilayer Perceptron (MLP) to conduct a single-blinded test on 10 independent PTC samples with unknown lymph node metastasis status.</div></div><div><h3>Results</h3><div>The SVM, and MLP algorithms achieved an accuracy of 100 % in differentiating PTC with or without LNM, while the RF and GBC algorithm reached an accuracy of 92 %. All four algorithms demonstrated an accuracy of 100 % in distinguishing PTC from adjacent normal tissues.</div></div><div><h3>Conclusion</h3><div>The combination of PESI - MS and AI exhibits high accuracy in predicting LNM in PTC and performs remarkably well in the rapid diagnosis of PTC. This approach can effectively assist in the rapid diagnosis of intraoperative pathology, assist in determining the surgical scope of thyroid lymph node dissection, and offer more precise treatment for patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155952"},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-HER2Net: A Generative Self-Supervised Framework for HER2 Classification in IHC Histopathology of Breast Cancer","authors":"Genevieve Chyrmang ,&nbsp;Barun Barua ,&nbsp;Kangkana Bora ,&nbsp;Gazi N Ahmed ,&nbsp;Anup Kr. Das ,&nbsp;Lopamudra Kakoti ,&nbsp;Bernardo Lemos ,&nbsp;Saurav Mallik","doi":"10.1016/j.prp.2025.155961","DOIUrl":"10.1016/j.prp.2025.155961","url":null,"abstract":"<div><div>Breast cancer is a significant global health concern, where precise identification of proteins like Human Epidermal Growth Factor Receptor 2 (HER2) in cancer cells via Immunohistochemistry (IHC) is pivotal for treatment decisions. HER2 overexpression is evaluated through HER2 scoring on a scale from 0 to 3+ based on staining patterns and intensity. Recent efforts have been made to automate HER2 scoring using image processing and AI techniques. However, existing methods require large manually annotated datasets as these follow supervised learning paradigms. Therefore, we proposed a generative self-supervised learning (SSL) framework “Self-HER2Net” for the classification of HER2 scoring, to reduce dependence on large manually annotated data by leveraging one of best performing four novel generative self-supervised tasks, that we proposed. The first two SSL tasks HER2_hsl and HER2_hsv are domain-agnostic and the other two HER2_dab and HER2_hae are domain-specific SSL tasks focusing on domain-agnostic and domain-specific staining patterns and intensity representation. Our approach is evaluated under different budget scenarios (2%, 15%, &amp; 100% labeled datasets) and also out distribution test. For tile-level assessment, HER2_hsv achieved the best performance with AUC-ROC of 0.965  ±  0.037. Our self-supervised learning approach shows potential for application in scenarios with limited annotated data for HER2 analysis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155961"},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMARCD1 is a dual regulator of PD-L1 expression and cell proliferation facilitating tumor evasion","authors":"Gang Fu ,&nbsp;Yutong Liu ,&nbsp;Chen Qian ,&nbsp;Zheyu Yang ,&nbsp;Maocai Luo ,&nbsp;Wei Cai","doi":"10.1016/j.prp.2025.155975","DOIUrl":"10.1016/j.prp.2025.155975","url":null,"abstract":"<div><h3>Purpose</h3><div>Cancer cells often evade immune responses by overexpressing immune checkpoint regulators, such as programmed cell death ligand 1 (PD-L1). Identifying targets that regulate PD-L1 is a promising approach for anti-tumor therapy.</div></div><div><h3>Methods</h3><div>Based on our previous CRISPR-Cas9 screening, we identified SMARCD1, a subunit of the mating-type switching/sucrose fermentation (SWI/SNF) complex, as a factor that promotes tumor evasion by inducing PD-L1-mediated immune checkpoint responses. Immunohistochemical staining (IHC) was used to assess SMARCD1 expression levels in colorectal cancer (CRC) and normal tissues. CRISPR-Cas9 technology was employed to generate SMARCD1 knockout (KO) cell lines. Western blotting and flow cytometry were used to evaluate PD-L1 expression. Cell proliferation, invasion, migration, and apoptosis were also assessed. A tumor model was established to examine the in vivo effects of SMARCD1. RNA-seq and ChIP-seq analyses were conducted to investigate the potential mechanisms.</div></div><div><h3>Results</h3><div>SMARCD1 was significantly upregulated in CRC tissues. In vitro, SMARCD1 regulated PD-L1 expression and significantly promoted tumor growth. The SWI/SNF inhibitor FHT-1015 reversed the effects of SMARCD1 knockout. Mechanistically, SMARCD1 may maintain chromatin accessibility at the PD-L1 transcriptional regulatory element and promote cancer cell proliferation via the PI3K-Akt signaling pathway.</div></div><div><h3>Conclusion</h3><div>SMARCD1 regulates PD-L1 transcription and facilitates tumor cell proliferation, making it a promising target for CRC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155975"},"PeriodicalIF":2.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SFPQ::TFE3-rearranged PEComa: Differences and analogies with renal cell carcinoma carrying the same translocation","authors":"Stefano Marletta ,&nbsp;Anna Caliò ,&nbsp;Francesco Pierconti ,&nbsp;Shuko Harada ,&nbsp;George J. Netto ,&nbsp;Pietro Antonini ,&nbsp;Diego Segala ,&nbsp;Serena Pedron ,&nbsp;Lisa Marcolini ,&nbsp;Lavinia Stefanizzi ,&nbsp;Guido Martignoni","doi":"10.1016/j.prp.2025.155963","DOIUrl":"10.1016/j.prp.2025.155963","url":null,"abstract":"<div><div>Among perivascular epithelioid cell neoplasms (PEComas), some tumors have been found to carry rearrangements of the <em>TFE3</em> gene. Such tumors can rarely occur in the kidney, closely resembling TFE3<em>-</em>rearranged renal cell carcinoma. This study describes one additional case of TFE3-rearranged PEComa, two TFE3-rearranged renal cell carcinomas, and a detailed literature review. All three tumors were composed of nested clear to eosinophilic cells with peculiar morphological findings in each case. By immunohistochemistry, PEComa expressed cathepsin K, HMB45, and CD68 (PG-M1), while labeling negative for PAX8, Melan-A, S100, smooth muscle actin, desmin<strong>,</strong> CD10, CD13, and keratins 7 and AE1/AE3. Conversely, both TFE3<em>-</em>rearranged renal cell carcinomas were positive for PAX8, HMB45, and CD10, alongside staining negative for CD68 (PG-M1), Melan-A, CD13, and keratins. One of them expressed cathepsin K. <em>TFE3</em> gene rearrangement was identified in all three cases by FISH, along with SFPQ::TFE3 fusion by molecular analysis. Our cases, combined with a comprehensive literature review, highlight several key differences and similarities: SFPQ::TFE3-rearranged PEComas lack the pseudorosettes frequently observed in SFPQ::TFE3-rearranged renal cell carcinoma, although both may exhibit nested epithelioid morphology. Both tumor types can be positive for cathepsin K and melanogenesis markers and negative for smooth muscle markers. However, PAX8, keratins, and CD10 were expressed in TFE3-rearranged renal cell carcinoma while CD68(PG-M1) was positive in PEComa. Notably, the <em>SFPQ</em> gene is the most common fusion partner in TFE3-rearranged PEComas, while it is the third most frequent one in TFE3-rearranged renal cell carcinoma. Nevertheless, the exon breakpoints are analogous in both tumor types.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155963"},"PeriodicalIF":2.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting KRAS-G12C in lung cancer: The emerging role of PROTACs in overcoming resistance","authors":"Kumarappan Chidambaram ,&nbsp;A. Rekha ,&nbsp;Ahsas Goyal ,&nbsp;Mohit Rana","doi":"10.1016/j.prp.2025.155954","DOIUrl":"10.1016/j.prp.2025.155954","url":null,"abstract":"<div><div>In lung cancer, KRAS mutations, especially the G12C, favor aggressive tumor growth and resistance to standard therapies. Although first-generation inhibitors of KRAS G12C, such as sotorasib and adagrasib, are highly effective in early-phase studies, resistance invariably develops under selective inhibition pressure and rarely leads to sustained long-term treatment benefits. As a novel approach to targeting KRAS mutations in lung cancer, PROTAC (Proteolysis Targeting Chimera) technology is explored in this review. The PROTACs take advantage of the cell’s ubiquitin-proteasome system to selectively degrade KRAS proteins, overcoming the dilemma of a lack of traditional binding sites and the means of resistance. We review recent progress with KRAS-specific PROTACs and their mechanisms, clinical application, and effectiveness at targeting primary KRAS oncogenes and secondary drivers and signaling pathways contributing to therapeutic resistance. Also, the synergies between PROTACs and immunotherapies or chemotherapies are further amplified. This review also underscores PROTAC technology’s promise to advance precision medicine by providing durable treatment options for KRAS-driven lung cancers. It addresses future directions for optimizing PROTAC efficacy, bioavailability, and patient-specific applications.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155954"},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the impact of chromosome 3p mutations in advanced renal cell carcinoma treated with immune-based combinations or targeted therapy: A single-center experience","authors":"Matteo Rosellini ,&nbsp;Veronica Mollica ,&nbsp;Andrea Marchetti ,&nbsp;Sara Coluccelli ,&nbsp;Francesca Giunchi ,&nbsp;Elisa Tassinari ,&nbsp;Linda Danielli ,&nbsp;Thais Maloberti ,&nbsp;Costantino Ricci ,&nbsp;Michelangelo Fiorentino ,&nbsp;Dario de Biase ,&nbsp;Francesco Massari","doi":"10.1016/j.prp.2025.155964","DOIUrl":"10.1016/j.prp.2025.155964","url":null,"abstract":"<div><h3>Background</h3><div>Immune-based combinations have transformed first-line treatment for metastatic renal cell carcinoma (mRCC), but reliable biomarkers for patient selection remain elusive. Chromosome 3p mutations (e.g., <em>VHL, PBRM1, SETD2, BAP1</em>) have shown inconsistent prognostic and predictive value. This retrospective study assessed the prognostic impact of tissue-based biomarkers, focusing on 3p mutations in mRCC.</div></div><div><h3>Patients and methods</h3><div>A single-center retrospective analysis included mRCC patients treated with immunocombinations or tyrosine kinase inhibitors (TKIs). We evaluated mutations in 14 genes, including <em>VHL, PBRM1, SETD2</em>, and <em>BAP1</em>. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Prognostic factors were analyzed using univariate and multivariate models.</div></div><div><h3>Results</h3><div>Among the included 38 patients, the most common mutations were in <em>VHL</em> (45 %), <em>PBRM1</em> (42 %), and <em>SETD2</em> (26 %), with these latter more frequent in males (<em>p</em> = 0.012). Most patients (74 %) received immune-based combinations; 26 % received TKIs. <em>SETD2</em> mutations were associated with primary refractoriness (30 %). Median OS was not reached; brain metastases (<em>p</em> = 0.001) and <em>BAP1</em> mutations (<em>p</em> = 0.025) predicted worse OS, while <em>PBRM1</em> mutations trended toward improved OS (<em>p</em> = 0.845). Median PFS was 14.1 months. Higher tumor grade (<em>p</em> = 0.038) and worse ECOG PS (<em>p</em> = 0.008) negatively impacted PFS, while 3p mutations showed no significant effect on PFS.</div></div><div><h3>Conclusions</h3><div>ECOG PS and brain metastases were confirmed as poor prognostic factors. <em>VHL</em> and <em>PBRM1</em> mutations may suggest a better prognosis, while <em>SETD2</em> and <em>BAP1</em> mutations portend worse outcomes. Larger studies are needed to confirm these findings.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155964"},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of combined loss of RB1, p53 and p21 in muscle-invasive bladder cancer","authors":"Benedikt Ebner ,&nbsp;Lennert Eismann ,&nbsp;Julian Hermans ,&nbsp;Marc Kidess ,&nbsp;Nikolaos Pyrgidis ,&nbsp;Marie Semmler ,&nbsp;Yannic Volz ,&nbsp;Alexander Buchner ,&nbsp;Michael Chaloupka ,&nbsp;Marie-Lisa Eich ,&nbsp;Philipp Weinhold ,&nbsp;Christian G. Stief ,&nbsp;David Horst ,&nbsp;Gerald B. Schulz ,&nbsp;Simon Schallenberg","doi":"10.1016/j.prp.2025.155960","DOIUrl":"10.1016/j.prp.2025.155960","url":null,"abstract":"<div><h3>Introduction</h3><div>Muscle-invasive bladder cancer (MIBC) represents a genetically heterogeneous disease with limited prognostic markers. This study aimed to validate the prognostic relevance of combined alterations in cell cycle regulators RB1, p53, and p21 in a broad cohort of MIBC patients undergoing radical cystectomy (RC).</div></div><div><h3>Material and Methods</h3><div>We analyzed formalin-fixed paraffin-embedded material from MIBC patients who underwent RC at the Department of Urology, University Hospital, Ludwig-Maximilians-University Munich. Tissue microarrays (TMAs) from 251 MIBC patients (pT2-pT4) were constructed, incorporating triplicate cores from tumor center and front. Immunohistochemical expression of RB1, p53, and p21 was assessed using a four-grade scoring system. Prognostic associations with overall survival (OS) and cancer-specific survival (CSS) were evaluated using multivariable Cox regression, Kaplan-Meier curves, and log-rank tests.</div></div><div><h3>Results</h3><div>We assessed 4518 stainings from 251 patients. Single marker analysis revealed no significant association between the loss of RB1, p53, or p21 and OS or CSS. However, the loss of two or three markers was significantly associated with worse OS (HR 3.49, 95 % CI 1.28–9.50; <em>p</em> = 0.01) and CSS (HR 11.2, 95 % CI 1.46–86.04; <em>p</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>RB1, p53, and p21 are insufficient as single prognostic markers in MIBC but demonstrate significant prognostic relevance when analyzed in combination. These findings underscore the need for multi-marker approaches in prognostic modeling and personalized treatment strategies for MIBC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155960"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating clinicopathological and molecular data to assess the biological behavior of uterine inflammatory myofibroblastic tumors","authors":"Quang Hiep Bui ,&nbsp;Michaela Krausová ,&nbsp;Nikola Hájková ,&nbsp;Jan Hojný ,&nbsp;Michaela Kendall Bártů ,&nbsp;Romana Vránková ,&nbsp;Marta Kalousová ,&nbsp;Filip Frühauf ,&nbsp;Michael Michal ,&nbsp;Kristýna Němejcová ,&nbsp;Ivana Stružinská ,&nbsp;Pavel Dundr","doi":"10.1016/j.prp.2025.155959","DOIUrl":"10.1016/j.prp.2025.155959","url":null,"abstract":"<div><div>Assessing the biological behavior of uterine inflammatory myofibroblastic tumors (IMTs) remains challenging. This study evaluated previously proposed risk schemes and features in 9 IMTs (6 indolent, 3 aggressive) by integrating clinicopathological features, immunohistochemistry, and next-generation sequencing (NGS). High-risk features (necrosis, infiltrative growth, nuclear atypia) were present in both groups, with LVSI in 1/3 of aggressive IMTs. Aberrant p16 expression and <em>CDKN2A/2B</em> deletions were noted in 2/3 aggressive cases. All cases harbored <em>ALK</em> fusions, wild-type p53, and lacked pathogenic gene mutations. Aggressive cases harbored arm-level and segmental copy number gains/losses at chr 1, 2, X, and had significantly reduced <em>AR</em> expression. The clinicopathological risk stratification score (CRSS) predicted the biological behavior correctly in cases with complete clinicopathological data (size, mitoses, age, infiltrative growth). Two morcellated cases (one indolent and one aggressive) would have been predicted as low risk based solely on the absence of pathogenic mutations. Hereby, the reliability of the proposed CRSS was confirmed. Aberrant p16 expression predicted malignant behavior in 2/3 aggressive cases. Absence of pathogenic mutations or presence of large scale CNVs does not seem to be a predictor of clinical behavior. Additional studies and NGS analyses of more cases may improve risk stratification for patients with incomplete clinicopathological information and may reveal additional risk stratifiers (such as the suggested large-scale CNVs or <em>AR</em> downregulation) for IMTs.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155959"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential: Receptor-mediated targeted drug delivery in cancer therapy","authors":"Balaji Palanisamy ,&nbsp;Abul Kalam Azad Mandal","doi":"10.1016/j.prp.2025.155955","DOIUrl":"10.1016/j.prp.2025.155955","url":null,"abstract":"<div><div>Receptor-mediated targeted drug delivery has emerged as a pivotal strategy in cancer therapy, offering precision and specificity in combating malignant diseases while minimizing systemic toxicity. This review explores the multifaceted role of receptors in cancer biology, emphasizing their contributions to cancer progression, metastasis, and their potential as therapeutic targets. Ligand-based targeting approaches highlight the utility of small molecules, peptides, and antibodies, as well as the development of novel targeting ligands. A critical focus is placed on engineering receptor-targeted nanoparticles and advanced drug delivery systems. Innovations in dual-targeting strategies and the targeted delivery to the tumour microenvironment (TME) and metastatic niches are discussed, underscoring their potential to enhance therapeutic efficacy. Additionally, receptor-targeted imaging is reviewed for its dual role in diagnosis and real-time treatment monitoring. To address the challenges of side effects and off-target toxicity, strategies that minimize these risks while targeting overexpressed receptors in solid tumours are explored. Finally, the review outlines future directions in receptor-targeted cancer therapy, emphasizing the need for interdisciplinary research to refine these strategies further. This comprehensive analysis aims to provide a roadmap for advancing receptor-based therapeutic approaches, ultimately improving outcomes for cancer patients.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155955"},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular pathways of advanced rectal cancer: A focus on genetic, RNA, and biological technique","authors":"Ameeduzzafar Zafar ,&nbsp;Mohammad Khalid ,&nbsp;Omar Awad Alsaidan ,&nbsp;Md Ali Mujtaba","doi":"10.1016/j.prp.2025.155956","DOIUrl":"10.1016/j.prp.2025.155956","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most frequently diagnosed cancer, with rectal cancer (RC) accounting for approximately 35 % of cases, posing a significant health burden. The early phase of R progression is characterized by the accumulation of genetic and epigenetic changes that promote cell growth. These rapidly dividing cells form a benign adenoma, which can eventually transform into malignant tumors and metastasize to other organs. Among the key molecular alterations, a mutation in the Wnt/β-catenin signaling pathway plays a crucial role. Additionally, BRAF mutation contributes to 8–10 % of CRC cases, while mutation in PIK3C pathways is responsible for 20–25 % of cases. The RC involves complex biological mechanisms. This review article highlights the pivotal role of mRNA in diagnosing and predicting the prognosis of RC, explores the various functions of non-coding RNAs (ncRNA,s), and examines the impact of RNA editing and modification on the progression of tumor genesis. Furthermore, we discuss the cellular signaling pathways and microenvironment interaction and pathways like PI3K/Akt/mTOR and Wnt/β-catenin. Advancements in molecular, RNA, and genetic research have evolved the treatment of cancer. Techniques like next-generation sequencing have tremendously opened the biological field of research. Along with this, techniques like CRISPR/Cas9 aid in the developing therapeutic strategies. Proteomics and metabolomics approach further contribute to novel research direction in oncology.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"270 ","pages":"Article 155956"},"PeriodicalIF":2.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}