The diagnostic value of multiple tumor markers in malignantovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

Study on combined assay for serum tumor markers in patients,with hepatic carcinoma

INTRODUCTIONSince the hepatic solid-occupying lesion (HSOL) wasfound by both ultrasonoscopy (US) and computed tomography(CT).If the customary alpha-fetoprotin (AFP) standard fordiagnosis primary hepatic carcinoma is used,those cancerswith lower AFP concentration may miss the diagnosis.Onthe other hand,the use of the standard:AFP-positive(≥20μg/L)+HSOL=primary hepatocellular carcinoma(PHCC),may yield false positive results.In order to ele-vate both the preoperative and differential diagnosis levels forhepatic carcinoma,we assayed combindedly the preoperativelevels of serum AFP,carbohydrate antibody (CA) 19-9 andcarcinoembryonic antigen (CEA) in the patients with HSOL.

Evaluation of the diagnostic value of tumor markers with ROC and logistic regression in gastrocolic tumors

Objective: The aim of the study was to evaluate the clinical significance of multiple tumor markers (CEA, AFP, CA72-4 and CA19-9) in patients with gastrocolic tumors by receiver operating characteristic (ROC) curve and stepwise logistic regression (LR) analysis. Methods: The serum concentrations of CEA, AFP, CA72-4 and CA19-9 were measured with electrochemiluminescence immunoassay in 126 patients with gastrocolic tumors, 137 patients with benign gastrocolic disorders and 109 healthy controls. The area under the ROC curve (AUC) of CEA, AFP, CA72-4 and CA19-9 and stepwise LR results were compared by sensitivity, specificity, Youden's index and positive likelihood ratio/negative likelihood ratio. Results: The levels of four tested tumor markers in patients with gastrocolic tumors were significantly higher than those in benign gastrocolic group and normal controls. In the benign gastrocolic group, the AUC from stepwise logistic regression was larger than the AUC of four tumor markers respectively. Sensitivity, Youden's index and positive likelihood ratio/negative likelihood ratio were the highest in the combination assay of CA72-4, CEA, and CA19-9, as compared with one of the tumor markers alone. Conclusion: The use of ROC established by LR analysis model improved the diagnostic accuracy of gastrocolic tumors. For the screening of gastrocolic tumors, the AUC value of the combination probability index (sensitivity and specificity) was significantly higher than the values of the different tumour markers.

Multiple biomarkers of colorectal tumor in a differential diagnosis model:A quantitative study

AIM:To evaluate the multiple biomarkers of colorectal tumor and their potential usage in early diagnosis of colorectal cancers. METHODS:Multiple biomarkers (DNA contents,AgNOR, PCNA,p53,c-erbB-2) in 10 normal colorectal mucosae,37 colorectal adenomas and 55 colorectal cancers were analyzed quantitatively in the computed processing imaging system. Discrimination patterns were employed to evaluate the significance of single and multiple indices in diagnosis of colorectal cancers. RESULTS:The mean values of the analyzed parameters increased in order of the normal mucosa,adenoma and adenocarcinoma,and this tendency reflected the progression of colorectal malignancy.The parameters including DNA index,positive rates,densities of AgNOR,c-erbB-2,and p53, shape and density of nucleus were relatively valuable for diagnoses.Then a diagnostic discrimination model was established.The samples were confirmed with the model, the sensitivity rates in cancer group and adenoma group were 96.36% and 89.19%,respectively.The value of proliferating cell nuclear antigen (PCNA) in early diagnosis of colorectal cancers was uncertain. CONCLUSION:The quantitative evaluation of some parameters for colorectal tumor can provide reproducible data for differential diagnosis.The established diagnostic discrimination model may be of clinicopathological value, and can make the early diagnosis of colorectal cancer possible.

CT Texture Analysis: A Potential Biomarker for Evaluating KRAS Mutational Status in Colorectal Cancer

Objective Texture analysis is deemed to reflect intratumor heterogeneity invisible to the naked eyes.The aim of this study was to evaluate the feasibility of assessing the KRAS mutational status in colorectal cancer(CRC)patients using CT texture analysis.Methods This retrospective study included 92 patients who had histopathologically confirmed CRC and underwent preoperative contrast-enhanced CT examinations.The patients were assigned into a training cohort(n=51)and a validation cohort(n=41).We placed the region of interest in the tumour regions on the selected axial images using software of lexRad to extract a series of quantitative parameters based on the spatial scaling factors(SSFs),including mean,standard deviation(SD),entropy,mean of positive pixels(MPP),skewness,and kurtosis.The texture parameters and clinical characteristics(age,gender,tumour location,histopathology;tumour size,1 N,M stages)were compared between the mutated and wild-type KRAS patient groups in training cohort and validation cohort.Before building the multiple feature classifier,we calculated the correlations of the features using Pearsons correlation coefficient,and if any two features were significantly correlated,the one with lower AUC was removed.Ultimately,only the most discriminative isolated features were combined to train a supporting vector machine(SVM)classifier.The receiver operating characteristic(ROC)curve was processed for evaluating the diagnostic efficiency of texture parameters in differentiating CRC patients with mutated KRAS from those with wild-type KRAS.Results None of the clinical characteristics were significant different between CRC patients with wild-type KRAS and mutated KRAS in both cohorts.For predicting the expression of mutated KRAS in CRC patients,the perfect model which combined skewness on SSF 5 by unenhanced CT,entropy on SSF 2,skewness and kurtosis on SSF 0,and kurtosis and mean on SSF 3 by enhanced CT,showed a desirable AUC of 0.951(95%CI:0.895-1,P<0.001),with a sensitivity of 88.9%and a specificity of 91.7%,when the cut-off value was 0.46 in the training cohort;while in the validation cohort,the AUC value was 0.995(95%CI:0.982-1,P<0.001),the sensitivity was 100%,and the specificity was 93.7%when the cut-off value was 0.28.Conclusion It is feasible to evaluate the KRAS mutational status in CRC using CT texture analysis.

Combined measurement of serum tumor markers in patients with hepatocellular carcinoma

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The prognostic molecular markers in hepatocellular carcinoma

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.

Cell-free plasma hypermethylated CASZ1, CDH13 and ING2 are promising biomarkers of esophageal cancer

Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma(ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450 K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1,CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.

Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer

Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia

AIM： To determine DNA aneuploidy in mucosal biopsies of achalasia patients for subsequent rapid diagnosis. METHODS： Biopsies from the middle third of the esophagus were obtained in 15 patients with achalasia. Immunohistochemical staining was carried out with monoclonal antibodies MIB-1 for Ki67 and PAb 1801 for p53, in addition to the conventional histologic examination for dysplasia. Nuclei of fresh biopsy material were enzymatically and mechanically isolated, and the DNA content was determined with image cytometry after Feulgen staining. DNA grading of malignancy was assessed according to Boecking to determine the variability of DNA values noted around the normal diploid peak. Further indices measured included the aneuploid rate, and the 5c-, 7c- and 9c-exceeding rate. RESULTS： The histological examination did not demonstrate dysplasia; while MIB-1 （basal） showed a positive reaction in 8/15 achalasia specimens, p53 was negative in all specimens. Image cytometric DNA analysis detected aneuploidy in 4/15 （26.7%） specimens. Samples from 15 patients with squamous cell carcinoma as well as specimens obtained exclusively 2 cm proximal to the tumor served as reference tests. All carcinomas （15/15） as well as 9 of the peritumoral samples （9/15） were aneuploid. The comparison of biopsies from achalasia patients with peritumoral and carcinoma specimens revealed statistically significant differences regarding the aneuploid rate （diploid： P 〈 0.0001; tetraploid： P = 0.001）, grading of malignancy according to Boecking （P 〈 0.0001） and the 5c- （P 〈 0.0001）, 7c-（P 〈 0.0001）, and 9c- （P = 0.0001） exceeding rate with progredient DNA alterations in the respective order. CONCLUSION： The finding that DNA aneuploidy was identified by image cytometry in esophageal specimens of patients with achalasia, which may be due to specific chromosomal alterations presenting as precancerous lesions in 27% of patients, leads us to conclude that image cytometry represents a valuable screening tool.

miR-93-5p/FOXJ2轴介导胃癌细胞的生物学功能

目的:评估miR-93-5p对胃癌细胞的调节和功能。方法:采用qPCR检测miR-93-5p在胃癌组织、胃癌细胞系中表达,MTT、克隆形成、Transwell实验检测miR-93-5p对胃癌细胞增殖、侵袭的影响,双荧光素酶报告基因实验检测miR-93-5p与FOXJ2的靶向关系。结果:miR-93-5p在胃癌细胞系和胃癌组织中表达升高,抑制miR-93-5p表达后胃癌细胞增殖和侵袭能力受抑。双荧光素酶报告基因检测显示,miR-93-5p mimic显著降低MKN28和MKN45细胞Wt-FOXJ2相对荧光素酶活性,FOXJ2为胃癌细胞中miR-93-5p的直接靶基因。结论:miR-93-5p靶向FOXJ2促进胃癌细胞的增殖和侵袭,miR-93-5p/FOXJ2轴可能是判断胃癌预后的生物标志物和治疗靶点。

叶酸受体阳性循环肿瘤细胞结合肿瘤标志物对肺癌诊断的研究

目的探讨叶酸受体阳性循环肿瘤细胞(FR^(+)-CTC)单独及联合肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)辅助诊断肺癌的有效性。方法收集2019年12月至2022年10月于四川省人民医院就诊的肺部结节患者的临床资料,根据结节的病理性质分为良性组188例和恶性组412例。分析FR^(+)-CTC与肺癌之间的关系,探讨联合检测肿瘤标志物对肺癌的诊断价值。结果恶性组FR^(+)-CTC水平高于良性组;恶性组中不同病理类型、TNM分期、临床分期患者的FR^(+)-CTC水平比较,差异有统计学意义(P<0.05)。FR^(+)-CTC在单独诊断肺癌的灵敏度、特异性均显著优于两种肿瘤标志物,联合诊断后FR^(+)-CTC在诊断肺癌的特异性方面有提升(P<0.05)。结论FR^(+)-CTC对于肺癌的诊断能力突出,可对患者病情进展、预后评估提供参考;联合肿瘤标志物能够提升诊断肺癌的特异性。

P53 immunohistochemical scoring:an independent prognostic marker for patients after hepatocellular carcinoma resection

AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (【10% -, 10-30% +, 31-50% ++, 】50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P【0.05) and capsule (P【0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P【0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P【0.01), vascular invasion (RI 0.5271, P【0.01) and capsule (RI-0.8691, P【0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P【0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.

DNA ploidy and c-Kitmutation in gastrointestinal stromal tumors

AIM: To investigate the prognostic significance of c-Kitgen emutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.

不同病理分级腹膜假黏液瘤:^(18)F-FDG PET/CT双时相显像表现及血清肿瘤标志物水平

目的对比不同病理分级腹膜假黏液瘤(PMP)^(18)F-FDG PET/CT双时相显像表现及血清肿瘤标志物水平。方法回顾性分析31例经病理确诊阑尾来源PMP患者,根据病理结果分为低级别、高级别及高级别伴印戒细胞PMP。对比不同级别PMP^(18)F-FDG PET/CT常规和延迟显像表现,以及PET/CT检查前1个月内血清癌胚抗原(CEA)、糖类抗原(CA)125及CA 19-9水平。结果31例PMP包括14例低级别、12例高级别及5例高级别伴印戒细胞PMP。^(18)F-FDG PET/CT延迟显像中,低、高级别PMP病灶最大标准摄取值(SUV_(max))、病灶SUV_(max)与肝脏平均标准摄取值之比(SUV_(max)/SUV_(livermean))及PET-腹膜癌指数(PCI)均高于常规^(18)F-FDG PET/CT显像(P均<0.05);延迟显像中,高级别伴印戒细胞PMP病灶SUV_(max)、SUV_(max)/SUV_(livermean)和PET-PCI均与常规显像差异均无统计学意义(P均>0.05)。不同病理分级PMP患者之间,CEA、CA 125及CA 19-9水平差异均无统计学意义(P均>0.05)。结论不同病理分级PMP的^(18)F-FDG PET/CT双时相显像表现具有一定特征性,血清肿瘤标志物水平与PMP病理分级无明显相关。

DNA倍体分析对液基细胞学在良恶性胸腹水诊断中的支持价值

目的:探讨液基细胞学、肿瘤标志物和DNA倍体分析单独和联合在良恶性胸腹水诊断中的鉴别价值。方法:收集312例同时做过胸腹水液基细胞学检查、DNA倍体分析和血清肿瘤标志物检测的病例,且所有病例都有组织病理诊断结果,对这些指标及人口统计学特征进行分析;基于液基细胞学、肿瘤标志物、DNA倍体分析单独及其组合的诊断,通过Logistic回归建立组合模型,并通过ROC曲线下面积(AUC)进行比较,以及计算其对应的敏感度(SE)、特异度(SP)、阳性预测值(PPV)和阴性预测值(NPV)。结果:以组织病理诊断结果为金标准,液基细胞学、肿瘤标志物和DNA倍体分析的AUC值分别是0.702、0.512、0.776;模型1(液基细胞学联合肿瘤标志物)AUC值为0.722,SE为49.8%,SP为90.6%,PPV为79.5%,NPV为24.5%;模型2(液基细胞学联合DNA倍体分析)AUC值为0.783,SE为68.7%,SP为83.00%,PPV为95.2%,NPV为35.2%;模型3(模型2联合肿瘤标志物)AUC值0.776,SE为58.7%,SP为88.7%,PPV为85.3%,NPV为29.8%;模型2表现出对良恶性胸腹水最高的诊断效率,液基细胞学和DNA倍体分析组合的AUC值高于液基细胞学(P<0.0001)和DNA倍体分析(P=0.3998)。结论:DNA倍体分析的诊断价值高于液基细胞学和传统肿瘤标志物;DNA倍体分析对液基细胞学在良恶性胸腹水的诊断中具有支持价值,提供了一种鉴别良恶性胸腹水的可靠模式。

肿瘤标志物在非小细胞肺癌诊断及病理分析中的应用研究

目的探究四种肿瘤标志物:癌胚抗原(CEA)、细胞角蛋白19血清片段21-1(CYFRA21-1)、糖类抗原(CA125)、鳞状细胞癌相关抗原(SCC)在非小细胞肺癌诊断及病理分析中的应用价值。方法选择2017年4月—2018年4月本院收治的700例肺部疾病患者为研究对象,根据患者病情分为对照组(良性肺部疾病,372例)和研究组(非小细胞肺癌,328例)两组。研究组根据患者不同病理类型又分为肺鳞癌组(201例)和肺腺癌组(127例)两组。观察比较两组患者体内四种肿瘤标志物的水平以及不同种类非小细胞肺癌内四种肿瘤标志物的阳性率。结果研究组患者体内的CEA、CA125、SCC肿瘤标志物的水平明显低于对照组,CYFRA21-1肿瘤标志物的水平明显高于对照组,差异有统计学意义(P<0.05);研究组中肺鳞癌患者中的SCC阳性率水平明显高于肺腺癌患者,差异有统计学意义(P<0.05)。结论根据癌胚抗原(CEA)、细胞角蛋白19血清片段21-1(CYFRA21-1)、糖类抗原(CA125)、鳞状细胞癌相关抗原(SCC)在不同患者血清内的水平差异使其作为4种血清肿瘤标志物检测非小细胞肺癌具有较高的特异性,能够提高对患者非小细胞肺癌诊断的敏感度,对非小细胞肺癌患者的诊断以及病理分析有较高的临床价值。因此,广大医学工作者应该加大对肿瘤标志物类型及其在不同疾病内含量水平差异的研究,不断创新非小细胞肺癌的检测方法,为临床上治疗非小细胞肺癌提供一种有效的检测依据。

TWIST2、SNAI1、TPX2及Aurora-A表达水平与喉鳞癌患者预后的相关性

目的对TWIST2、SNAI1、TPX2及Aurora-A表达水平与喉鳞癌患者预后的相关性进行分析。方法将2016年1月至2020年12月于我院诊治的103例喉鳞癌患者纳入研究,术前检测患者血TPX2水平,术中留取肿瘤组织,检查肿瘤组织中TWIST2、SNAI1及Aurora-A表达水平。根据患者2年随访结果将患者分为预后良好组(n=71)及预后不良组(n=29),比较并分析两组患者一般资料及实验室指标,绘制并应用受试者工作(ROC)曲线评估影响因素预测患者预后的诊断价值。结果预后良好组患者的年龄,肿瘤Ⅳ期、低分化-未分化及SNAI1、Aurora-A及TPX2表达水平均显著低于预后不良组,而TWIST2显著高于预后不良组(均P<0.05);CoX分析示,高SNAI1、Aurora-A及TPX2表达水平是患者预后的独立危险因素,而高TWIST2表达水平为预后独立保护因素;根据治疗方案及术式对患者进行分层,分析TWIST2、SNAI1、TPX2及Aurora-A水平对预后的影响差异有统计学意义(均P<0.05);随访1年时,ROC曲线示TWIST2、SNAI1、Aurora-A及TPX2表达水平联合预测患者预后的诊断效能与TWIST2、SNAI1、Aurora-A及TPX2单一诊断效能相比较,差异无统计学意义(均P<0.05),TWIST2、SNAI1、Aurora-A及TPX2表达水平联合预测患者预后的敏感度为100.0%,特异度为91.6%;随访2年时,ROC曲线示TWIST2、SNAI1、Aurora-A及TPX2表达水平联合预测患者预后的诊断效能显著高于TWIST2、SNAI1、Aurora-A及TPX2单一诊断(均P<0.05),TWIST2、SNAI1、Aurora-A及TPX2表达水平联合预测患者预后的敏感度为93.1%,特异度为87.3%。结论TWIST2、SNAI1、Aurora-A及TPX2联合诊断能有效预测患者预后,具有较高特异度及敏感度。

肿瘤标志物及EMT通路表达水平对黑色素瘤预后的影响

目的探讨上皮-间充质转化(EMT)通路对黑色素瘤患者预后的影响及黑色素瘤常见肿瘤标志物与EMT通路的相关性,为临床识别和随访高转移风险的黑色素瘤患者提供新思路。方法从TCGA数据库中获得461例黑色素瘤患者的转录及临床数据,通过GSVA包对每个样本的表达进行非参数的无监督分析,得到EMT通路的表达评分并分为低和高两组,使用Survival包进行生存分析。随后对肿瘤标志物的mRNA和EMT通路表达水平进行Spearman相关性分析,并根据年龄、性别和肿瘤分期进行亚组分析。进一步从TCGA数据库中下载黑色素瘤患者肿瘤标志物的蛋白表达水平,同样进行Spearman相关性分析,从mRNA和蛋白表达水平2个角度探讨常见肿瘤标志物与EMT通路的相关性。最后将上述肿瘤标志物、EMT通路表达水平和临床特征纳入多因素分析以明确对黑色素瘤预后的影响。结果EMT通路的高表达预示黑色素瘤患者的不良预后。黑色素瘤肿瘤标志物PMEL、MLANA、TYR和MITF的mRNA表达水平与EMT通路呈负相关(P<0.05),MKI67的mRNA表达水平与EMT通路呈正相关(P<0.05)。肿瘤标志物与EMT通路相关性的亚组分析结果与总样本中所得结果基本一致。肿瘤标志物PMEL高表达和EMT相关通路低表达时预示良好预后,EMT相关通路低表达时MLANA、MKI67低表达预示良好预后(P<0.05)。PMEL、MLANA和MITF的蛋白表达水平与EMT通路的表达呈负相关(P<0.05)。PMEL、年龄和病理分期是影响黑色素瘤预后的独立危险因素(P<0.05)。结论黑色素瘤的常见肿瘤标志物PMEL、MLANA和MITF较低表达可能与EMT通路的高表达相关;EMT相关通路低时,PMEL与MLANA高表达、MKI67低表达预示良好预后,随访中应给予一定程度重视。