This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry...This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry (IHC). The predominance of female breast cancer (30%) aligns with global trends, underscoring the need for robust diagnostic protocols, particularly in developing regions. Other prevalent cancers, including skin, stomach, and cervix uteri, reflect a mix of environmental, genetic, and infectious factors. The underrepresentation of gallbladder and thyroid cancers (<1%) suggests potential underdiagnosis or lower prevalence. Age distribution data indicate peak cancer incidence in individuals aged 31 - 45 years, with gender-specific cancers like breast and cervical cancer predominantly affecting females (63.4%). The analysis also highlights significant diagnostic gaps, as 61.2% of cases did not undergo IHC testing due to resource constraints, leading to potential biases in cancer prevalence and diagnostic accuracy. The study emphasizes the complementary role of IHC in confirming ambiguous H&E findings, with strong alignment observed when both methods were used. However, the absence of IHC in many cases limits the robustness of conclusions, suggesting the need for increased access to IHC testing. The findings advocate for integrating IHC into routine diagnostics, expanding diagnostic capabilities, and improving sample sizes to ensure more reliable and comprehensive cancer data.展开更多
BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited trea...BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.展开更多
BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in pa...BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
文摘This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry (IHC). The predominance of female breast cancer (30%) aligns with global trends, underscoring the need for robust diagnostic protocols, particularly in developing regions. Other prevalent cancers, including skin, stomach, and cervix uteri, reflect a mix of environmental, genetic, and infectious factors. The underrepresentation of gallbladder and thyroid cancers (<1%) suggests potential underdiagnosis or lower prevalence. Age distribution data indicate peak cancer incidence in individuals aged 31 - 45 years, with gender-specific cancers like breast and cervical cancer predominantly affecting females (63.4%). The analysis also highlights significant diagnostic gaps, as 61.2% of cases did not undergo IHC testing due to resource constraints, leading to potential biases in cancer prevalence and diagnostic accuracy. The study emphasizes the complementary role of IHC in confirming ambiguous H&E findings, with strong alignment observed when both methods were used. However, the absence of IHC in many cases limits the robustness of conclusions, suggesting the need for increased access to IHC testing. The findings advocate for integrating IHC into routine diagnostics, expanding diagnostic capabilities, and improving sample sizes to ensure more reliable and comprehensive cancer data.
基金Supported by Seoul National University Bundang Hospital Research Fund,No.06-2021-0140National Research Foundation of Korea,No.RS-2024-00335454.
文摘BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.
基金Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220521Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA147The National College Students’Innovation and Entrepreneurship Training Program,No.202310598042.
文摘BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.
文摘目的基于定量蛋白质组学探讨补肾益精方治疗2型糖尿病骨质疏松症(type 2diabetic mellitus osteoporosis,T2DOP)可能涉及的药理作用及机制。方法将60只SPF级雄性Wistar大鼠随机选取10只作空白组,其余50只大鼠参照唐辉的方法通过腹腔注射链脲佐菌素构建T2DOP大鼠模型。将符合T2DOP模型的大鼠随机分为模型组、阳性对照组、补肾益精方低、中、高剂量组,分别给予生理盐水、阿仑膦酸钠和低、中、高剂量补肾益精方灌胃干预8周。期间记录大鼠一般情况、血糖和体质量的变化;干预结束后取大鼠股骨使用Micro-CT进行扫描,并对骨松质进行3D重建和参数分析;苏木精—伊红染色观察大鼠股骨组织形态改变。根据Micro-CT及苏木精—伊红染色结果,选择补肾益精方中一组与模型组、空白组以稳定同位素二甲基化标记的方法运用定量蛋白质组学技术探究补肾益精方干预T2DOP的蛋白网络及作用机制筛选出差异蛋白,蛋白质印迹法、免疫组化检测验证差异蛋白。结果(1)Micro-CT扫描3D重建及苏木精—伊红染色结果显示,补肾益精方可以改善T2DOP大鼠模型的骨代谢平衡、改善骨微结构和增强骨力学性能。(2)通过蛋白质组学得出,空白组与模型组比较,筛选到107差异蛋白(上调蛋白82个,下调蛋白24个);补肾益精方高剂量组与模型组比较,筛选到78个差异蛋白(上调蛋白15个,下调蛋白63个)。对筛选的差异蛋白分别进行了基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(KyotoEncyclopedia of Genes and Genomes,KEGG)分析和蛋白质—蛋白质相互作用(Protein-ProteinInteraction,PPI)网络分析,发现23个差异蛋白之间存在相互作用,形成了一个复杂的调控网络,网络中的核心蛋白包括MMP9、TNF、Akt1,这些核心蛋白在PPI网络中处于枢纽位置。结论补肾益精方通过MMP9、TNF、Akt1等核心基因蛋白的表达,抑制骨吸收,促进骨形成,从而达到防治T2DOP目的。
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
