Pathobiology最新文献

{"title":"Hepatic Progenitor Cells in the Form of Ductular Structures within a GIST Liver Metastasis: Supporting a Putative Role in the Hepatic Metastatic Niche.","authors":"João Lobo, João Gama, Rita Luis, Dina Tiniakos, Maria Augusta Cipriano","doi":"10.1159/000531456","DOIUrl":"10.1159/000531456","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have highlighted the presence of hepatic progenitor cells (HPCs) in metastatic liver carcinomas. We provide further evidence of this phenomenon, presenting a case of a gastrointestinal stromal tumour (GIST) liver metastasis with evidence of intra- and peritumoral HPC.</p><p><strong>Case description: </strong>A 64-year-old man presented with a gastric mass diagnosed as a high-risk KIT-mutated GIST. The patient was treated with imatinib, recurring 5 years later with a liver mass. Liver biopsy disclosed a GIST metastasis, hallmarked by a proliferation of ductular structures without cytological atypia intermingled with the tumour cells, with a CK7/CK19/CD56-positive immunophenotype and rare CD44 positivity. The patient underwent liver resection, and the same ductular structures were present in the tumour interior and at its periphery.</p><p><strong>Conclusion: </strong>We document for the time the presence of HPC in the form of ductular structures in a GIST liver metastasis, further supporting their role in the liver metastatic niche.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"417-421"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598919","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":"Senescent Tumor Cells Are Frequently Present at the Invasion Front: Implications for Improving Disease Control in Patients with Locally Advanced Prostate Cancer.","authors":"Sebastian Schwarz,&nbsp;Cathleen Nientiedt,&nbsp;Elena-Sophie Prigge,&nbsp;Adam Kaczorowski,&nbsp;Christine Geisler,&nbsp;Carlota Lucena Porcel,&nbsp;Magnus von Knebel Doeberitz,&nbsp;Markus Hohenfellner,&nbsp;Stefan Duensing","doi":"10.1159/000530430","DOIUrl":"10.1159/000530430","url":null,"abstract":"<p><strong>Introduction: </strong>Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular, seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease.</p><p><strong>Methods: </strong>The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer. Prostate cancer specimens were stained by double-immunohistochemistry for the proliferation marker Ki-67 and the senescence marker p16INK4A. The migratory properties of senescent prostate cancer cells were analyzed in vitro using a wound healing assay and immunofluorescence microscopy for p16INK4A.</p><p><strong>Results: </strong>We confirm the notion that patients with SVI have a more unfavorable prognosis than patients with extraprostatic extension alone. Surprisingly, we found that the tumor invasion front frequently harbors p16INK4A-positive and Ki-67-negative, i.e., senescent, tumor cells. While the intraprostatic tumor periphery was a hotspot for both proliferation and expression of p16INK4A, the area of SVI showed less proliferative activity but was at the same time a hotspot of cells with increased nuclear p16INK4A expression. Senescence was associated with an accelerated migration of prostate cancer cells in vitro.</p><p><strong>Conclusion: </strong>This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"312-321"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227777","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":"Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.","authors":"Diogo Sousa Marques, Irene Gullo, Luís Mascarenhas-Lemos, João Ricardo Silva, Catarina Neto do Nascimento, Patrícia Pontes, Lídia Pinho, Luis Cirnes, Xiaogang Wen, Marília Cravo, Fátima Carneiro","doi":"10.1159/000530997","DOIUrl":"10.1159/000530997","url":null,"abstract":"<p><strong>Introduction: </strong>Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative.</p><p><strong>Methods: </strong>In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0.</p><p><strong>Results: </strong>PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla.</p><p><strong>Conclusion: </strong>IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"389-399"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9565366","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":"Lymphocyte Subsets in Cervicovaginal Lavage Specimens of HIV-Infected Women: A Surrogate Risk Marker of HPV-Associated Cervical Lesions.","authors":"Maria Jose Brito,&nbsp;Ana Quintas,&nbsp;Filipa Passos,&nbsp;Ana Teresa Alves,&nbsp;Ana Félix,&nbsp;Catarina Gregório Martins","doi":"10.1159/000526965","DOIUrl":"https://doi.org/10.1159/000526965","url":null,"abstract":"<p><strong>Introduction: </strong>To better understand the role of mucosa immunity in the development of cervical carcinoma in HIV infection, cervical lymphocyte subsets were characterized in HIV+ and HIV- women, as well as their relation to HPV-associated cervical lesions.</p><p><strong>Methods: </strong>Eighty-three (52 HIV+, 31 HIV-) cell suspensions of cervicovaginal lavage (CVL) and 52 HIV+ peripheral blood (PB) samples were assessed by flow cytometry to evaluate lymphoid populations. High-risk (HR) HPV was assessed in liquid-based cytology and HIV mRNA in PB in the same patients.</p><p><strong>Results: </strong>Cervical CD4+ T cells and CD4+/CD8+ ratio were decreased (p < 0.0001) and cervical CD8+ T cells were increased (p = 0.0080) in HIV+ women. These patients had lower CD4+ T-cell percentages in CVL compared to PB (p = 0.0257), and the opposite was true for CD8+ T cells (p = 0.0104). They also had a higher prevalence of high-grade squamous intraepithelial lesions (SILs) with an increased prevalence of HR HPV. Cervical CD8+ T cells were increased in HR HPV+ patients (p = 0.0300) and related to higher prevalence of SILs (p = 0.0001).</p><p><strong>Discussion/conclusion: </strong>Cervical lymphoid populations can be characterized by flow cytometry, showing a distinct cervical T-cell compartment in HIV+ women. This may represent a surrogate risk marker of HPV-associated cervical lesions in this population and prompt further research on this subject, contributing to improving patients' management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 3","pages":"176-186"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572269","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":"A Comparison of Tissue Dissection Techniques for Diagnostic, Prognostic, and Theragnostic Analysis of Human Disease.","authors":"Elise M Walsh, Marc K Halushka","doi":"10.1159/000525979","DOIUrl":"10.1159/000525979","url":null,"abstract":"<p><p>Histopathology has historically been the critical technique for the diagnosis and treatment of human disease. Today, genomics, transcriptomics, and proteomics from specific cells, rather than bulk tissue, have become key to understanding underlying disease mechanisms and rendering useful diagnostic information. Extraction of desired analytes, i.e., nucleic acids or proteins, from easily accessible formalin-fixed paraffin-embedded tissues allows for clinically relevant activities, such as sequencing biomarker mutations or typing amyloidogenic proteins. Genetic profiling has become routine for cancers as varied as non-small cell lung cancer and prostatic carcinoma. The five main tissue dissection techniques that have been developed thus far include: bulk scraping, manual macrodissection, manual microdissection, laser-capture microdissection, and expression microdissection. In this review, we discuss the importance of tissue dissection in clinical practice and research, the basic methods, applications, as well as some advantages and disadvantages for each modality.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 3","pages":"199-208"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650414","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":"Autoimmune Thyroiditis Induced by Bartonella henselae (Cat-Scratch Disease) Might Be Reversible.","authors":"Marek Niedziela,&nbsp;Jarosław Szydlowski,&nbsp;Michal Dopierala,&nbsp;Jadwiga Maldyk,&nbsp;Iwona Klimecka,&nbsp;Pawel Kurzawa","doi":"10.1159/000525399","DOIUrl":"https://doi.org/10.1159/000525399","url":null,"abstract":"<p><strong>Introduction: </strong>Bartonella henselae infection leads to development of cat-scratch disease (CSD) but may also trigger of autoimmune thyroiditis (AIT).</p><p><strong>Case presentation: </strong>We describe a 4-year-old boy with a severe fever of unknown etiology, disseminated neck lymphadenopathy, and a headache. Treatment with antibiotics was employed, but finally a left tonsillectomy, selective left lymphadenectomy, and immunophenotyping were performed to exclude lymphoma. Histologic examination excluded lymphoma but revealed CSD. IgG against B. henselae and Bartonella quintana was positive. A goiter was also found and positive anti-thyroid antibodies confirmed AIT. Two months later, the thyroid was not palpable, normal on ultrasound, and both anti-thyroid antibodies were negative. The full reversibility was documented, and 6-year follow-up showed that the patient remains disease free.</p><p><strong>Conclusion: </strong>This is the first report that AIT triggered by B. henselae/B. qunitana might be reversible if the pathogenetic factor is eliminated at an early stage of disease.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 2","pages":"131-137"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9676411","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":"Low-Dose Alcohol-Induced Inhibition of Mouse Orthotopically Transplanted Tumors Is Associated with T-Cell Response.","authors":"Akiko Kimoto,&nbsp;Shoma Kunisho,&nbsp;Ryohei Morita,&nbsp;Minako Onishi,&nbsp;Qian Zhou,&nbsp;Atsushi Ono,&nbsp;Daiki Miki,&nbsp;Fumio Shimamoto,&nbsp;Yasuhiko Kitadai","doi":"10.1159/000524478","DOIUrl":"https://doi.org/10.1159/000524478","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers and heavy drinkers. This phenomenon has been labeled the \"J-curve effect\" of alcohol. This study examined the effects of low-dose alcohol (0.5%, 1%, and 2%) on tumor growth in a transplant colon cancer model.</p><p><strong>Methods: </strong>BALB/c and BALB/c nude mice were used to analyze T-cell immunity. Syngeneic CT26 murine colon cancer cells were implanted into the cecal wall, and the resulting T-cell immune effects were monitored.</p><p><strong>Results: </strong>The growth of orthotopic tumors was markedly inhibited upon ingestion of low-dose (0.5%) alcohol compared with that in the control mice. In contrast, cells from the same line were injected into the cecal wall of nude mice, and tumor growth inhibition was not observed. Histopathological and RNA sequence analyses were performed to elucidate the mechanisms underlying tumor growth inhibition. An increase in tumor CD8+ T lymphocytes and changes in cytokine levels were observed. Microbiome analysis using 16S rRNA gene sequencing of cecal contents was performed and revealed Mucispirillum schaedleri and Clostridium cocleatum showed decreased and increased abundance, respectively, in the alcohol group.</p><p><strong>Discussion/conclusion: </strong>Ingesting a threshold amount of alcohol results in the infiltration of T lymphocytes, which may enhance immune responsiveness in mouse colorectal cancer models.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 1","pages":"22-30"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10620523","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":"Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine.","authors":"Eiichi Morii,&nbsp;Yutaka Hatanaka,&nbsp;Noriko Motoi,&nbsp;Akihiko Kawahara,&nbsp;Shinji Hamakawa,&nbsp;Takeshi Kuwata,&nbsp;Tadasuke Nagatomo,&nbsp;Yoshinao Oda,&nbsp;Aikou Okamoto,&nbsp;Ryota Tanaka,&nbsp;Akira Iyoda,&nbsp;Maeda Ichiro,&nbsp;Yukiko Matsuo,&nbsp;Nobuyuki Nakamura,&nbsp;Tokiko Nakai,&nbsp;Mei Fukuhara,&nbsp;Kazuya Tokita,&nbsp;Tomohiko Yamaguchi,&nbsp;Masataka Takenaka,&nbsp;Ayako Kawabata,&nbsp;Kanako C Hatanaka,&nbsp;Kaho Tsubame,&nbsp;Yukitoshi Satoh","doi":"10.1159/000528346","DOIUrl":"10.1159/000528346","url":null,"abstract":"<p><p>Rapid advances are being made in cancer drug therapy. Since molecularly targeted therapy has been introduced, personalized medicine is being practiced, pathological tissue from malignant tumors obtained during routine practice is frequently used for genomic testing. Whereas cytological specimens fixed mainly in alcohol are considered to be more advantageous in terms of preservation of the nucleic acid quality and quantity. This article is aimed to share the information for the proper handling of cytological specimens in practice for genomic medicine based on the findings established in \"Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine (in Japanese)\" published by the Japanese Society of Clinical Cytology in 2021. The three-part practical guidelines are based on empirical data analyses; Part 1 describes general remarks on the use of cytological specimens in cancer genomic medicine, then Part 2 describes proper handling of cytological specimens, and Part 3 describes the empirical data related to handling of cytological specimens. The guidelines indicated proper handling of specimens in each fixation, preparation, and evaluation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"289-311"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10674953","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":"Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2.","authors":"Yue-E Chen,&nbsp;Fu-le Ren,&nbsp;Xing Gu,&nbsp;Hong-Jun Zhang,&nbsp;Wen-Jie Li,&nbsp;Han Yang,&nbsp;Fen-Qing Shang","doi":"10.1159/000528318","DOIUrl":"https://doi.org/10.1159/000528318","url":null,"abstract":"<p><strong>Introduction: </strong>The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta.</p><p><strong>Methods: </strong>This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization.</p><p><strong>Results: </strong>Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta.</p><p><strong>Conclusion: </strong>Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 4","pages":"241-250"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940264/pdf/pat-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959930","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":"Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer.","authors":"Narutaka Katsuya,&nbsp;Akira Ishikawa,&nbsp;Aya Kido,&nbsp;Takafumi Fukui,&nbsp;Go Kobayashi,&nbsp;Yohei Sekino,&nbsp;Naohiro Uraoka,&nbsp;Takashi Babasaki,&nbsp;Wataru Yasui,&nbsp;Kazuhiro Sentani,&nbsp;Naohide Oue","doi":"10.1159/000525590","DOIUrl":"https://doi.org/10.1159/000525590","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) is a leading cause of cancer-related death worldwide. This study focused on minichromosome maintenance 4 (MCM4), a DNA helicase component that functions in DNA replication. Using spheroid colony formation, having a colony rich in cancer stem cells, this study aimed to investigate the clinicopathological importance of MCM4.</p><p><strong>Methods: </strong>We examined MCM4 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analysis in 10 and 113 GC cases, respectively. MCM4 function in GC was also investigated by RNA interference in GC cell lines.</p><p><strong>Results: </strong>In qRT-PCR and IHC analysis, high MCM4 expression was found in 60% and 83% of GC cases, respectively. MCM4-positive GC cases were significantly associated with higher T grade and tumor stage. Additionally, high MCM4 expression was significantly associated with poor prognosis and was an independent prognostic factor in multivariate analysis. MCM4 was significantly coexpressed with CD133, matrix metalloproteinase 7 (MMP7), epidermal growth factor (EGFR), and mesenchymal-epithelial transition factor (cMET). In GC cell lines, MCM4 knockdown affected cell growth and protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and EGFR pathways.</p><p><strong>Conclusion: </strong>These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 3","pages":"147-154"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007487","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}