Pathology, research and practice最新文献

{"title":"Cuproptosis: A new mechanism for anti-tumour therapy","authors":"Dong Wang ,&nbsp;Haoran Guan","doi":"10.1016/j.prp.2024.155790","DOIUrl":"10.1016/j.prp.2024.155790","url":null,"abstract":"<div><div>As an indispensable trace metal element in the organism, copper acts as a key catalytic cofactor in a wide range of biological processes. Copper homeostasis disorders can be caused by either copper excess or deficiency, and copper homeostasis disorders will affect the normal physiological functions of cells and induce cell death through a variety of mechanisms, such as the emerging cuproptosis model. The imbalance of copper homeostasis will lead to the occurrence of cancer, and copper is a key factor in cell signalling, so copper is involved in the development of cancer by promoting cell proliferation, angiogenesis and metastasis, etc. The therapeutic role of Cuproptosis as a hotspot of research in cancer has also attracted much attention. Therefore, this paper comprehensively searches the literature to review the roles and mechanisms of Cuproptosis in the treatment of malignant tumours, aiming to provide new insights into the role and mechanism of Cuproptosis in anti-malignant tumour therapy and present novel ideas and methods.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155790"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896664","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":"Loss of tumor cell surface hepatocyte growth factor activator inhibitor-1 predicts worse prognosis in esophageal squamous cell carcinoma","authors":"Yoshiko Umekita ,&nbsp;Takumi Kiwaki ,&nbsp;Makiko Kawaguchi ,&nbsp;Koji Yamamoto ,&nbsp;Makoto Ikenoue ,&nbsp;Shinsuke Takeno ,&nbsp;Tsuyoshi Fukushima ,&nbsp;Yuichiro Sato ,&nbsp;Hiroaki Kataoka","doi":"10.1016/j.prp.2025.155809","DOIUrl":"10.1016/j.prp.2025.155809","url":null,"abstract":"<div><div>Hepatocyte growth factor activator inhibitor-1 (HAI-1) is an epithelial type-1 transmembrane protease inhibitor that regulates the pericellular activities of hepatocyte growth factor activator and type-2 transmembrane serine proteases. It is strongly expressed in the stratified squamous epithelium and functions on the cell surface. We previously reported that the cell surface immunoreactivity of HAI-1 was reduced at the invasion front of oral squamous cell carcinoma. In this study, we investigate the relationship between cell surface HAI-1 (csHAI-1) and prognosis of esophageal squamous cell carcinoma (ESCC) after surgery. The effect of HAI-1 knockdown on cultured ESCC cells was also analyzed <em>in vitro</em>. HAI-1 exhibited distinct cell surface immunoreactivity in normal esophageal epithelium. In contrast, alterations in HAI-1 immunoreactivity were frequent in cancer cells, which exhibited aberrant intracytoplasmic localization and decreased cell surface immunoreactivity. The preservation of csHAI-1 immunoreactivity was a sign of a well-differentiated phenotype of ESCC cells. The decreased csHAI-1 was associated with shorter overall survival (OS) and disease-free survival (DFS) in the patients. In 55 cases of early (T1) ESCC cases, decreased csHAI-1 also predicted poor OS and DFS. The loss of HAI-1 enhanced migration and invasion of ESCC cells <em>in vitro</em>. These results suggest that the decreased cell surface immunoreactivity of HAI-1 is associated with a less differentiated phenotype and worse prognosis in ESCC. The cell surface-localized HAI-1 may serve as a promising marker for predicting recurrence and prognosis of ESCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155809"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTEN regulation in virus-associated cancers","authors":"Shaian Tavakolian ,&nbsp;Zahra Shokati Eshkiki ,&nbsp;Abolfazl Akbari ,&nbsp;Ebrahim Faghihloo ,&nbsp;Seidamir Pasha Tabaeian","doi":"10.1016/j.prp.2024.155749","DOIUrl":"10.1016/j.prp.2024.155749","url":null,"abstract":"<div><div>Despite advancements in science, researchers still face challenges in curing patients with malignancies. This health issue is linked to various risk factors, including alcohol consumption, age, sex, and infectious diseases. Among these, viral agents play a significant role in cancer-related health problems and are currently a subject of ongoing research. In this review, we summarize how several viruses—such as herpesviruses, human papillomavirus, hepatitis B virus, hepatitis C virus, and adenovirus—impact cancer signaling pathways through their effects on the tumor suppressor PTEN.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155749"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792218","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":"Lipid-laden uterus: Investigating uterine fibroids and lipid association","authors":"Sandeepa KN ,&nbsp;Shilpa S. Shetty ,&nbsp;Prasannakumar Shetty","doi":"10.1016/j.prp.2024.155772","DOIUrl":"10.1016/j.prp.2024.155772","url":null,"abstract":"<div><div>Uterine Fibroids (UF) are the most common (about 70 % cases) benign gynecological smooth muscle tumors of the uterus in women of reproductive age, characterized by abnormal cholesterol, lipoproteins, and triglyceride levels, and are a major public health concern. Despite its high prevalence, this condition remains complex and poorly understood. These tumors are hormone-dependent and hormones and lipid levels are inversely related. This review delves into the existing literature and critically evaluates studies that explore the potential relationship between lipids in the pathogenesis of uterine fibroids. This review concludes by critically appraising the research gaps in the involvement of lipids and signaling pathways in the pathogenesis of uterine fibroids and future directions for investigating this intriguing biological connection. By elucidating the potential link between uterine fibroids and lipids, this review paves the way for an improved understanding of fibroid pathogenesis, personalized risk assessment, and novel lipid-lowering therapeutic strategies.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155772"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877819","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":"The functional role of LncRNA HOXA-AS2 in multiple human cancers","authors":"Mohadeseh khoshandam ,&nbsp;Nikolaos Sideris ,&nbsp;Amirhossein Ahmadieh-Yazdi ,&nbsp;Mohsen Sheykhhasan ,&nbsp;Hamed Manoochehri ,&nbsp;Hamid Tanzadehpanah ,&nbsp;Hanie Mahaki ,&nbsp;Mona Ghadam ,&nbsp;Shermin lak ,&nbsp;Naser Kalhor ,&nbsp;Mohammad Rabiei ,&nbsp;Sharafaldin Al-Musawi ,&nbsp;Paola Dama","doi":"10.1016/j.prp.2024.155795","DOIUrl":"10.1016/j.prp.2024.155795","url":null,"abstract":"<div><div>Humans have more than 270,000 lncRNAs. Among these, lncRNA HOXA-AS2 is considered a transformative gene involved in various cellular processes, including cell proliferation, apoptosis, migration, and invasion. Thus, it can be regarded as a potential tumor marker for both diagnosis and prognosis. Aberrant expression of lncRNAs is associated with many cancers, including hepatocellular carcinoma (HCC), gallbladder carcinoma (GBC), acute promyelocytic leukemia (APL), lung cancer (LC), prostate cancer (PC), osteosarcoma (OS), colorectal cancer (CRC), cervical cancer (CC), and acute myeloid leukemia (AML). Targeting lncRNAs could be a promising strategy to complement or replace current cancer treatments. As a non-coding oncogene, lncRNA HOXA-AS2 is implicated in multiple cancers and could serve as a potential biomarker for various malignancies. The tumor size and disease stage of several cancers are correlated with HOXA-AS2 expression. Silencing HOXA-AS2 effectively suppresses tumor cell proliferation and promotes apoptosis, thereby inhibiting the progression of multiple cancer types. The regulatory mechanisms of HOXA-AS2 include inducing epithelial-mesenchymal transition (EMT), overexpressing B-cell lymphoma-2 (Bcl-2) and MYC proto-oncogene (c-Myc), gene silencing, activating AKT-MMP signaling pathways, EZH2 and LSD1, and functioning within a competing endogenous RNA (ceRNA) regulatory network by competitively binding miRNAs. This review surveys recent research on the structure, biological functions, abnormal expression, regulatory mechanisms, and diagnostic and therapeutic potential of HOXA-AS2 in various cancers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155795"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932434","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":"Clinicopathologic and genomic characteristics of biliary tract carcinomas with TERT promoter mutations among East Asian population","authors":"Inwoo Hwang ,&nbsp;So Young Kang ,&nbsp;Deok Geun Kim ,&nbsp;Kee‑Taek Jang ,&nbsp;Kyoung-Mee Kim","doi":"10.1016/j.prp.2024.155806","DOIUrl":"10.1016/j.prp.2024.155806","url":null,"abstract":"<div><div>Telomerase reverse transcriptase gene promoter (<em>TERT</em>) mutations are biomarkers that predict survival and responses to immune checkpoint inhibitors in various malignancies. However, their prevalence and clinicopathologic characteristics in biliary tract carcinomas are largely unknown. We performed a comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 485 carcinomas, including intrahepatic (n = 220), perihilar (n = 54), distal biliary tract (n = 110), and gallbladder (n = 101) cancers, using next-generation sequencing. <em>TERT</em> mutations were observed in 50 out of 485 biliary tract cancers (10.3 %) consisting of 39 C228T (78.0 %) and 11 C250T (22.0 %) variants. Among the different anatomic locations, <em>TERT</em> mutations were most frequent in the gallbladder (20.8 %), followed by perihilar (9.3 %), intrahepatic (7.7 %), and distal bile ducts (6.4 %) (<em>p</em> &lt; 0.01). Genetically, <em>TERT</em> mutations were significantly associated with <em>TP53</em> mutations (<em>p</em> = 0.04), <em>ERBB2</em> amplification (<em>p</em> &lt; 0.01), and high tumor mutational burdens (TMB) (<em>p</em> &lt; 0.01); moreover, they were negatively correlated with <em>KRAS</em> (p &lt; 0.01), <em>SMAD4</em> (<em>p</em> = 0.01), and <em>PBRM1</em> mutations (<em>p</em> = 0.01). In addition, <em>TERT</em> mutations were associated with a poor progression-free survival (PFS, <em>p</em> = 0.01). Specifically, in cases of intrahepatic cholangiocarcinoma, <em>TERT</em> mutations were more frequent in patients with cirrhosis (<em>p</em> = 0.01), hepatitis B virus infection (<em>p</em> = 0.04), and advanced disease stages (<em>p</em> &lt; 0.01). In gallbladder carcinoma, <em>TERT</em> mutations were also associated with poor PFS. In conclusion, <em>TERT</em> mutations in biliary tract carcinomas had unique clinicopathologic and genetic characteristics. Despite its poor PFS, the concomitant presence of <em>ERBB2</em> amplification and a high TMB indicated a potential for targeted therapy and immunotherapy in this specific subtype.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155806"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allelic variants in xenobiotic metabolism genes predict susceptibility and worse prognosis of urothelial bladder cancer","authors":"Isabely Mayara da Silva ,&nbsp;Flora Troina Maraslis ,&nbsp;Julia Ayumi Ikeda Kawasaki ,&nbsp;Natieli Kazue Aida ,&nbsp;Gustavo Rafael Mazzaron Barcelos ,&nbsp;Alexsandro Koike ,&nbsp;Paulo Emílio Fuganti ,&nbsp;Ilce Mara de Syllos Cólus ,&nbsp;Roberta Losi Guembarovski ,&nbsp;Juliana Mara Serpeloni","doi":"10.1016/j.prp.2024.155767","DOIUrl":"10.1016/j.prp.2024.155767","url":null,"abstract":"<div><div>Biomarkers that identify tumors with better/worse prognosis can help reduce treatment costs and contribute to patient survival. In urothelial bladder cancer (UBC), accurate prediction of recurrence and progression is essential to inform therapeutic management. Herein, we explore the role of genetic variants of xenobiotic metabolic pathways in UBC susceptibility and prognosis. In total, 295 participants with UBC and 295 controls were genotyped using TaqMan® probes. <em>CYP1A1 (rs1048943), CYP3A4 (rs4646437), CYP3A5 (rs4646450), UGT2B7 (rs7438135),</em> and <em>UGT2B15 (rs3100)</em> allele frequencies were compared between UBC patients and controls and were analyzed concerning tumor grade, invasion, and recurrence. <em>CYP3A4</em> (AA) increased susceptibility to UBC 3-fold when interacting with <em>CYP3A5</em> (AA+AA). The susceptibility was higher in <em>CYP3A4</em> (AA) males (OR=3.189) and individuals exposed to pesticides (OR=5.492). When interacting with hypertension, the allele C of <em>CYP1A1</em> also increased UBC susceptibility by 2-fold. The <em>UGT2B15</em> mutant allele was associated with high-grade tumors (OR=2.196) and recurrences (OR=2.561), as well as tumor grade when associated with mutated alleles of <em>CYP3A4</em> (OR=6.171) and <em>CYP3A5</em> (OR=3.492). Genes-encoding proteins were further analyzed using the STRING program, demonstrating that the proteins had known interactions in databases and were co-expressed. This study is a pioneer in evaluating these variants in a Latin American population from Brazil and confirms occupational pesticide exposure as a risk factor for UBC, mainly in genetically susceptible individuals. Furthermore, these variants may have additional clinical value for predicting susceptibility and prognostic stratification in patients with exposure-related cancers such as UBC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155767"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896663","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":"LncRNA CRNDE and HOTAIR: Molecules behind the scenes in the progression of gastrointestinal cancers through regulating microRNAs","authors":"Mohamed J. Saadh ,&nbsp;Soumya V. Menon ,&nbsp;Rajni Verma ,&nbsp;G.V. Siva Prasad ,&nbsp;Omer Qutaiba B. Allela ,&nbsp;Morug Salih Mahdi ,&nbsp;Nabeel Ahmad ,&nbsp;Beneen Husseen","doi":"10.1016/j.prp.2024.155778","DOIUrl":"10.1016/j.prp.2024.155778","url":null,"abstract":"<div><div>Gastrointestinal (GI) cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and esophageal cancer, pose a significant medical and economic burden globally, accounting for the majority of new cancer cases and deaths each year. A lack of knowledge about the molecular mechanisms of GI cancers is reflected in the low efficacy of treatment for individuals with late stage and recurring illness. Understanding the molecular pathways that promote the growth of GI cancers may open doors for their therapy. Numerous long non-coding RNAs (lncRNAs) that are produced differently in normal and malignant tissues have been discovered by genome-wide techniques. The role of lncRNAs in the diagnosis, proliferation, metastasis, and drug resistance of different GI cancers has been investigated in recent research. LncRNAs may affect transcription, epigenetic modifications, protein/RNA stability, translation, and post-translational modifications via their interactions with DNA, RNAs, and proteins. Also, by functioning as competing endogenous RNAs (ceRNAs), they control the synthesis of certain microRNAs (miRNAs), which in turn modify the downstream target molecules of these miRNAs. Based on recent studies, lncRNAs in particular, CRNDE and HOTAIR, sponge different miRNAs and their downstream genes, which in turn regulate GI cancers development, including cell proliferation, invasion, migration, and chemoresistance. In this comprehensive review, we present an overview of the biological roles of CRNDE and HOTAIR and their associated mechanisms, miRNAs/mRNA pathways, in various GI cancers, encompassing colorectal cancer, hepatocellular carcinoma, esophageal cancer, and gastric cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155778"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896665","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":"Novel therapeutic approaches targeting cancer stem cells: Unveiling new frontiers in breast cancer treatment","authors":"Deeptha T.C. ,&nbsp;Nabeela N.K. ,&nbsp;Charumathi Pushparaj ,&nbsp;Arul Narayanasamy ,&nbsp;Paulpandi Manickam ,&nbsp;Saranya Thiruvenkataswamy ,&nbsp;Ramya Sennimalai","doi":"10.1016/j.prp.2024.155800","DOIUrl":"10.1016/j.prp.2024.155800","url":null,"abstract":"<div><div>Breast cancer remains the leading cause of mortality among women with cancer. This article delves into the intricate relationship between breast cancer and cancer stem cells (CSCs), emphasizing advanced methods for their identification and isolation. The key isolation techniques, such as the mammosphere formation assay, surface marker identification, Side Population assay, and Aldehyde Dehydrogenase assay, are critically examined. Furthermore, the review analyzes CSC-specific molecular signaling pathways, focusing on actionable targets like CD44/CD24, Nanog, and Oct4. The potential of targeted therapies and small molecules that disrupt these pathways is explored. Additionally, the review highlights immunotherapy strategies against CSCs, focusing on resistance mechanisms and the critical role of precision medicine. The study investigates how precision medicine enhances therapeutic outcomes by targeting specific CSC biomarkers. This comprehensive analysis offers insights into recent advancements and emerging strategies in breast cancer treatment, pointing toward future therapeutic innovations.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155800"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984372","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":"Elevated expression of REV7 correlates with poor prognosis in lung adenocarcinoma and its inactivation in carcinoma cells enhances chemosensitivity","authors":"Shoko Hayashi ,&nbsp;Masaaki Ichinoe ,&nbsp;Yasutaka Sakurai ,&nbsp;Yurika Kesen ,&nbsp;Takuya Kato ,&nbsp;Itaru Sanoyama ,&nbsp;Akiyoshi Hoshino ,&nbsp;Kazu Shiomi ,&nbsp;Masashi Mikubo ,&nbsp;Yukitoshi Satoh ,&nbsp;Yoshiki Murakumo","doi":"10.1016/j.prp.2024.155779","DOIUrl":"10.1016/j.prp.2024.155779","url":null,"abstract":"<div><div>REV7 is a multifunctional protein involved in the DNA damage response, cell cycle regulation, gene expression, or primordial germ cell maintenance. REV7 expression in tumor cells is associated with clinical aggressive features and chemoresistance in several human malignancies, however, the clinicopathological significance of REV7 in lung adenocarcinoma (LUAD) has not been studied yet. In this study, we investigated the significance of REV7 expression in LUAD using clinical materials and cell lines. REV7 expression in 142 invasive LUADs were determined using immunohistochemistry, and the relationship between REV7 expression and clinicopathological features was analyzed. High levels of REV7 expression in tumor tissues were positively associated with progressive tumor behavior as assessed by Ki-67 labeling indexes (<em>p</em> &lt; 0.001), maximum standardized uptake values on positron emission tomography (<em>p</em> = 0.005), pathological stage (<em>p</em> = 0.031), N factor (<em>p</em> = 0.048), recurrence (<em>p</em> = 0.038), and disease-specific death (<em>p</em> = 0.020). The REV7-high-expression group showed poorer relapse-free survival (RFS) (<em>p</em> = 0.025) and overall survival (OS) (<em>p</em> = 0.019) compared to the REV7-low-expression group, and REV7 was a significant prognostic factor for RFS and OS. CRISPR/Cas9-mediated <em>REV7</em>-knockout and siRNA-mediated <em>REV7</em> knockdown were carried out using the LUAD cell lines A549 and H1975, respectively, and it was demonstrated that REV7 inactivation led to slower cell growth, attenuated activation of AKT signaling, and enhanced chemosensitivity compared with control cells. These results suggest that REV7 is a potential predictive biomarker for poor prognosis in invasive LUAD and a possible molecular target for LUAD management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155779"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872717","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}