Evaluation of a newly developed HIV antigen test

A new monoclonal antibody-based enzyme immunoassay (Innogenetics) for the detection and quantification of p24 core antigens of HIV-1 (group M and group O) and of HIV-2 was evaluated on 2745 serum samples and 18 culture supernatants and compared with a reference (Coulter) HIV-1 p24 antigen assay. Positive results were confirmed by neutralization with the reagents of the respective tests. As demonstrated by dilution series of HIV cocultures, the new test recognizes p24 antigen of the most common HIV genetic subtypes, including group O and HIV-2. Titres ranged from 729 to 531441. Therefore p24 antigen assay is but very weakly reactive with HIV-2 (titres from 9 to 81). The new test is considerably more sensitive than the reference. In a population of 365 follow-up samples from 86 different patients, representing all stages of infection, the new test detected p24 antigen at least once in 52% (45/86) of these patients, whereas the reference was positive in 31% (27/86). The newly designed test detected antigen in 40% (145/365) of the samples, while the reference was positive in 21% (75/365). In a group of PCR and/or culture positive neonates, 33% (9/27) of the samples were positive with the new test versus 18% (5/27) with the reference. The specificity of the new test, as determined on 2,000 blood donor samples, was 99.65% (initially), 99.80% (after repetition), and 100% (with neutralization). The reference scored 99.95%, 100%, and 100%, respectively. In 300 seronegative samples from persons at risk, the initial specificity of the new test was 98.67% (the reference, 99.00%). With neutralization, both assays were 100% specific. J. Med. Virol. 53:31–35, 1997. © 1997 Wiley-Liss, Inc.     

The Diversity of Antigen-Specific TCR Repertoires Reflects the Relative Complexity of Epitopes Recognized

Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 K^d. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252–260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170–179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant H-2 K^d molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/K^d complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.     

Combined detection of preoperative serum CEA,CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients

We assessed the prognostic significance of preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) levels in surgically treated colorectal cancer patients. The relationship of preoperative serum CEA, CA19-9 and CA242 levels with disease characteristics was investigated in 310 patients. Correlation between tumor markers was investigated using Pearson correlation test. Univariate and multivariate survival analyses were used to study the relationship between preoperative tumor markers and prognosis [disease free survival (DFS) and overall survival (OS)]. Kaplan-Meier analysis with log rank test was used to assess the impact of tumor marker levels on survival. Positive rate of preoperative serum CEA, CA19-9 and CA242 were 54.84%, 47.42% and 37.10%, respectively. High preoperative CEA level was associated with tumor size (P = 0.038), T stage (P < 0.001) and AJCC stage (P = 0.002). High preoperative CA19-9 level was associated with tumor AJCC stage (P = 0.023). Preoperative CA242 positively correlated with CEA (P < 0.001) and CA19-9 (P < 0.001). Combining the three markers was of independent prognostic value in CRC (HR = 2.532, 95% CI: 1.400-4.579, P = 0.002 for OS; and HR = 2.366, 95% CI: 1.334-4.196, P = 0.003 for DFS). Combined detection of preoperative serum CEA, CA19-9 and CA242 is of independent prognostic value for management of CRC patients treated surgically.     

Expression of mucin antigens and Lewis X-related antigens in carcinomas and dysplasia of the pharynx and larynx

Recent studies have Identified that much antigens and Lewis X (Le^x)-related antigens behave like oncodevelopmental tumor-asnoclated antigens in several human adenocarcino-mas. However, the expression of these antigens In pharyn-geal and latyngeal squamous cell carcinomas (SCC) and in the precursor lesion is not fully elucidated yet. In the present study, the expression of mucin core protein antigens associated with the MUC1 gene product (DF3 antigen, mammary-type apomucin) and the MUC2 gene product (intestinal-MRP antigen, Intestinal-type apomucin) much carbohydrate antigens that are associated with the earliest steps in mucin glycosylation (Tn, sialyl-Tn and T), and Le^x -related antigens (Le^x, Leγ and slayl Le^x-1) In biopsy or resected specimens from 26 normal squamous epithelia (NSE), 49 dysplastic squamous epithelia (DSE) and 51 SCC were examined. The DF3 antigen was not expressed In NSE (0%), whereas it was expressed in 20 DSE (41%) and in 31 SCC (61%). The intestinal-MRP antigen showed no expression in NSE, DSE or SCC. The Tn antigen showed no expression in NSE, but showed low expression rates In DSE (14%) and in SCC (16%). The sialyl-Tn and T antigens were expressed in NSE, as well as in DSE and SCC. The T antigen expression increased with progression from NSE to DSE to SCC, while the sialyl-Tn antigen did not show such a tendency. Any of the three Le^x-related antigens showed no characteristic expression in DSE and SCC. In the eight antigens examined, only DF3 antigen was an effective marker for DSE and SCC in the pharyngeal and laryngeal region. Cytoplasmic expression of DF3 and slalyl- Tn antigens were more frequently seen In SCC than in DSE, and might be useful to differentiate SCC from DSE.     

Differential up-regulation of HLA-DM, invariant chain, and CD83 on myeloid and plasmacytoid dendritic cells from peripheral blood

Two main dendritic cell (DC) subsets have been described in peripheral blood, the myeloid subset or DC1 that is characterized by the presence of CD11c and the plasmacytoid subset or DC2 negative for this marker. The two subsets may perform different functions and have been defined as immunogenic (the myeloid subset) or tolerogenic (the plasmacytoid subset). The expression of human leukocyte antigen (HLA)-DM molecules, which act as peptide editors in the antigen presentation process, was studied in freshly isolated plasmacytoid and myeloid DCs from peripheral blood. The expression of the invariant chain (Ii), the major histocompatibility complex class II (MHC-II) : class II-associated Ii peptide (CLIP) complex, and CD83 was also investigated. The results showed that intracellular expression of HLA-DM and the Ii was significantly higher in the plasmacytoid than in the myeloid DC subset. In contrast, a higher fraction of cell expressing MHC-II : CLIP complex was found in the myeloid than in the plasmacytoid DC subpopulation. CD83 was not detected in any of these two subsets. Following culture of these cells with interleukin-3 (IL-3), tumor necrosis factor-alpha (TNFalpha) and/or heat shock protein-70 (HSP-70), the expression of intracellular HLA-DM was up-regulated in the myeloid DCs to levels similar to those found in the plasmacytoid DCs, whilst the Ii was down-regulated in the plasmacytoid subset to similar levels to those expressed in the myeloid DCs. In addition, CD83 was up-regulated in the myeloid (CD11c+) but not in the plasmacytoid (CD11c-) DCs. The expression pattern of these antigen-processing molecules could be related to the immaturity and function attributed to these DC subsets.     

抗巨细胞病毒早晚期抗原单克隆抗体制备及在病毒培养物鉴定中的初步应用

目的 制备抗CMV早晚期抗原单克隆抗体并在病毒培养物鉴定中初步应用.方法 CMV感染MRC-5细胞24h、48h和72h后甲醛灭活的可溶性抗原免疫BALB/c小鼠,小鼠脾细胞与骨髓瘤细胞NS-1进行融合.酶免法筛查阳性杂交瘤并有限性稀释法进行克隆.免疫荧光及印迹对筛选后的克隆进行鉴定,最终获得的杂交瘤制备腹水并使用Protein G进行纯化.纯化后单抗应用于CAP室间质评标本以及临床标本CMV培养物的鉴定.结果 3只小鼠脾细胞与骨髓瘤细胞融合后初步筛查出约110株阳性克隆.剔除与其它抗原有交叉反应、抗体效价低、非全覆盖早晚期抗原的克隆最终获得抗CMV单抗杂交瘤1株,即23B5-1.免疫荧光显示23B5-1株单抗与CMV感染后3h-120h的MRC-5细胞均反应,即覆盖即刻、早期和晚期抗原.免疫印迹试验显示23B5-1株单抗与CMV抗原25KD-50KD之间的5个蛋白条带结合.23B5-1株单抗免疫球蛋白亚型为IgG1.Protein G纯化腹水后的单抗效价≥1∶12800.纯化单抗染色鉴定6份室间质评及10份临床标本CMV培养物全部符合.结论 初步应用显示制备的抗CMV早晚期抗原单克隆抗体性能良好.     

Development and Characterisation of Recombinant Hepatitis Delta Virus-like Particles

Injection of particulate hepatitis B virus surface antigen (HBsAg) in mice leads to the induction of a HBsAg-specific class-I-restricted cytotoxic T lymphocyte (CTL) response. It is proposed that any protein internal to HBsAg will also be able to elicit a specific CTL response. In this study, several carboxy-terminal truncations of hepatitis C virus (HCV) core protein were fused to varying lengths of amino-terminal truncated large hepatitis delta antigen (L-HDAg). These constructs were analysed for their ability to be expressed and the particles secreted in the presence of HBsAg after transfection into HuH-7 cells. The secretion efficiency of the various HCV core-HDAg chimeric proteins was generally poor. Constructs containing full length HDAg appeared to be more stable than truncated versions and the length of the inserted protein was restricted to around 40 amino acids. Thus, the use of L-HDAg as a chimera to package foreign proteins is limited. Consequently, a polyepitope (polytope) containing a B-cell epitope from human papillomavirus (HPV 16) and multiple T-cell epitopes from the HCV polyprotein was used to create the construct, L-HDAg-polyB. This chimeric protein was shown to be reliant on the co-expression of HBsAg for secretion into the cell culture fluid and was secreted more efficiently than the previous HCV core-HDAg constructs. These L-HDAg-polyB virus-like particles (VLPs) had a buoyant density of approximately 1.2 g/cm3 in caesium chloride and approximately 1.15 g/cm3 in sucrose. The VLPs were also immunoprecipitated using an anti-HBs but not an anti-HD antibody. Thus, these recombinant VLPs have similar biophysical properties to L-HDAg VLPs.     

The Fertilization Antigen (FA-1): Applications in Immunocontraception and Infertility in Humans

ABSTRACT: GB24 is a mouse monoclonal antibody (IgG1) raised against human term placental microvilli. This antibody displayed pan-trophoblast reactivity pattern. In addition, GB24 recognized normal peripheral leukocytes and transformed cell lines (Daudi, HL-60, Jurkat, AV₃, BeWo, HT-29) by using membrane immunofluorescence and flow cytometry. By SDS-polyacrylamide gel electrophoresis, this antibody immunoprecipitated two proteins of 62 kilodaltons (kDa) and 75 kDa from placental microvilli. Isoelectrofocusing analysis revealed that these two bands exhibited different isoelectric points: 4.7 for the 62 kDa protein, 4.6 and 4.4 for the two spots corresponding to the 75 kDa protein. Microvilli from different placentae revealed substantial differences regarding the intensity of the labeling of these two bands, suggesting that the antigens recognized by GB24 are probably allotypic.     

Identification of a dominant immunogenic epitope of the nucleocapsid (HBc) of the hepatitis B virus

Four monoclonal antibodies to hepatitis B core antigen are described. The antibodies bind to the same or a very closely related epitope. Antibodies to this dominant epitope are present in the sera of patients with either acute or chronic hepatitis B virus (HBV) infection. A high percentage of inhibition of the binding of these antibodies to the core antigen by these four monoclonal antibodies suggests that the core antigen has a restricted antigenicity in man. Radiolabeled or peroxidase labeled forms of these monoclonal antibodies can be used to assay IgM and total anticore in serum.     

tPSA和cPSA对前列腺疾病诊断的临床价值

为了进一步探讨血清总前列腺特异性抗原(tPSA)和复合前列腺特异性抗原(cPSA)对前列腺疾病诊断的临床价值,用CLIA检测良性前列腺增生(BPH)组30例、前列腺癌(Pca)组30例患者和对照组45名血清tPSA和cPSA水平,比较各组间差异。结果表明:Pca组患者血清tPSA和cPSA水平较对照组及BPH组有显著性差异(P<0.01)。血清tPSA在低水平(4.0~10.0ng/mL),即“灰色区域”内,cPSA与tPSA对Pca组的阳性预测值比较有显著性差异(P<0.01)。Pca组联检tPSA cPSA的阳性率与单检tPSA或cPSA的阳性率比较有显著性差异(P<0.05)。本研究认为:tPSA、cPSA均是诊断与鉴别诊断Pca和BPH的重要指标。对Pca的诊断,血清tPSA在4.0~10.0ng/mL时,cPSA优于tPSA。联检tPSA cPSA可明显提高对早期Pca诊断的准确率。     

Exponential Rise in Prostate-Specific Antigen (PSA) during Anti-Androgen Withdrawal Predicts PSA Flare after Docetaxel Chemotherapy in Patients with Castration-Resistant Prostate Cancer

PurposeTo investigate the relationship between rising patterns of prostate-specific antigen (PSA) before chemotherapy and PSA flare during the early phase of chemotherapy in patients with castration-resistant prostate cancer (CRPC).ResultsThere were two growth patterns of PSA doubling time: 22 patients (40.0%) had a steady pattern with a more prolonged PSADT2 than PSADT1, while 33 (60.0%) had an accelerating pattern with a shorter PSADT2 than PSADT1. During three cycles of chemotherapy, PSA flare occurred in 11 patients (20.0%); of these patients, 3 were among 33 (9.1%) patients with an accelerating PSA growth pattern and 8 were among 22 patients (36.4%) with a steady PSA growth pattern (p=0.019). Multivariate analysis showed that only PSA growth pattern was an independent predictor of PSA flare (p=0.034).ConclusionAn exponential rise in PSA during anti-androgen withdrawal is a significant predictor for PSA flare during chemotherapy in CRPC patients.     

Characterization of a monoclonal antibody (BG3C8) that reacts with basal cells of stratified epithelia

Monoclonal antibodies were produced against a suspension of formaldehyde fixed human epidermal cells. The supernatant fluid of one clone (BG3C8) yielded a bright immunofluorescent staining of basal cells both in cryostat sections of human split skin and in preparations of purified basal cells. As determined by one- and two-dimensional gel immunoblotting of epidermal basal cell proteins the antibody recognized a minor basic polypeptide of 55,000 apparent molecular weight that was not present in extracts of cultured cell lines of epithelial, fibroblast and lymphoid origin. The distribution of the 55,000 molecular weight protein in normal human tissue was determined by immunohistological staining of cryostat tissue sections that included: central nervous, endocrine, female and male reproductive, alimentary, lymphatic-haemopoietic, respiratory and urinary systems, skin and its appendages, mesenchymal tissue (bone, cartilage, muscle, connective tissue, blood vessels, nerves and synovia) as well as placenta and umbilical cord. The results showed a restricted distribution of this antigen which was found only in basal cells of most stratified or pseudostratified epithelia and in myoepithelial cells. This antibody may be useful in the study of normal and pathological differentiation in various epithelial disorders.     

Combined immunohistochemical study of tissue polypeptide antigen and cancer antigen 125 in human ovarian tumours

An indirect immunoperoxidase method was used to study the expression of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA 125) in 47 benign and malignant ovarian tumours. Tissue polypeptide antigen and CA 125 antigen were expressed respectively in 22 (73%) and 16 (53%) of the 30 adenocarcinomas and in five (29%) and four (23%) of the 17 benign tumours. Co-expression of TPA and CA 125 antigen occurred in 12 (40%) malignant and four (23%) benign tumours. Ultrastructurally, TPA and CA 125 antigens were located at the cell surface and microvillous surfaces. Evaluation of combined TPA and CA 125 antigen results revealed a remarkable improvement in the positivity rate and a significant decrease (P less than 0.05) in the negativity rate of ovarian carcinomas as compared with the result of each one separately. These findings provide complementary evidence for the previous results on the plasma levels of TPA and CA 125 antigen and suggest that specific combinations of tumour markers may be more effective for the diagnosis and monitoring of ovarian carcinomas, than the use of any single marker.     

Physicochemical heterogeneity of hepatitis B e antigen detected in asymptomatic carriers and carriers in a hemodialysis unit.

Physicochemical studies of hepatitis B e antigen (HBeAg) revealed a clear cut difference between e1 and e2 antigen. The e1 antigen was found to have a MW of Ca 150,000 and a pI of 6.4-7.2, whereas both the MW and pI of the e2 antigen were heterogeneous depending upon the source of serum. Sera obtained from asymptomatic carriers were characterized by low titers of HBs antigen, HBc antigen and DNA polymerase and contained e2 antigen of larger molecular weight (200,000-300,000) with a narrow distribution range and a pI of 4.8 to 5.2 (type 1). On the other hand, the sera from patients in a hemodialysis unit who were HBs antigen carriers and had high titers of HBs antigen, HBc antigen and DNA polymerase contained e2 antigen of heterogeneous distribution in MW (from 300,000 to 70,000) and pI (type 2 and 3). The e2 antigen obtained from the higher MW type 3 serum had lower isoelectric points (pI 4.5 to 5.2) as was the case with e2 antigen obtained from asymptomatic carriers whereas relatively wide range of isoelectric points (pI 5.1 to 8.2) was found with the lower molecular weight e2 antigen.     

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections

Gondak R O, Alves D B, Silva L F F, Mauad T & Vargas P A
(2012) Histopathology  60, 497–503
Depletion of Langerhans cells in the tongue from patients with advanced‐stage acquired immune deficiency syndrome: relation to opportunistic infections Aims: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non‐AIDS patients with normal tongues, using autopsy material. Methods and results: Human leucocyte antigen D‐related (HLA‐DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)‐negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a⁺ cells (P < 0.001), HLA‐DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non‐AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. Conclusions: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.     

Epstein-Barr virus serology in bone marrow transplantations: a one-year retrospective study with detection of EBV IgM-VCA-specific antibodies

The specific antibody response to Epstein-Barr virus (EBV) antigens of 41 bone marrow transplant recipients with leukemia or aplastic anemia was examined retrospectively by immunofluorescence test (IF) over 1 year. We observed high titers (greater than 640) of IgG-viral capsid antigen (VCA) with emergence of IgG-early antigen (EA) and frequent absence or low levels of Epstein-Barr nuclear antigen (EBNA) antibodies. After absorption to remove rheumatoid factor (RF), five of the 41 recipients had IgM-VCA antibody to EBV, which appeared between weeks 26 and 48 after BMT and persisted for 1-4 months. No heterophil antibodies were detected in these sera, and none of the five recipients had a history of infectious mononucleosis.     

Altered expression of Lewis blood group and related antigens in fetal,normal adult and malignant tissues of the uterine endometrium

Summary The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronouned in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues.Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium.Supported in part by a Grant-in-Aid for Scientific Research (62480346) from the Ministry of Health and Welfare     

Extraction,purification of prostate-specific antigen (PSA), and establishment of radioimmunoassay system as a diagnostic tool for prostate disorders

This study aimed to provide an easy and effective method for extraction and purification of prostate-specific antigen (PSA) from human seminal fluid with high quantity (14 mg) and high purity (98%). The obtained PSA was injected into rabbits for production of anti-PSA polyclonal antibody (titer 1/1000), labeled with radioactive iodine-125 for preparation of radioactive PSA tracer (purity 98 ± 1.8% and specific activity 64 ± 1.9 µCi/µg), and used in preparation of PSA standards. All prepared components can be used in PSA immunoassays specially radioimmunoassay (RIA) kit preparation as a diagnostic tool for prostatic diseases.     

Rapid production of monoclonal antibodies to T lymphocyte functional antigens

Brief immunization of rats with mouse lymphoid cells was combined with the rat/mouse hybridoma technology and functional hybridoma screening to yield a rapid method for the production of monoclonal antibodies (MAb) against functionally important T lymphocyte cell surface antigens. Two protocols were used. In one, rats were immunized once with mouse thymocytes followed by fusion and screening of the hybridomas for interference with the thymocyte co-stimulator (interleukin 1) assay. The resultant hybridomas included producers of MAbs against the L3T4-antigen (inhibitory), the Ly-1-antigen (stimulatory), and the Thy-1-antigen (inhibitory?). In the second protocol, rats were immunized twice with a T cell hybridoma. The resultant hybridomas were screened for inhibition of polyclonal T cell activation, induced by an anti-Thy-1 (MAb G7). A panel of MAbs against the Thy-1 antigen with different reactivity profiles was generated by this procedure. Most of the MAbs were of the IgM class. Short-term immunization may lead to less selection of response to highly immunogenic determinants than a protocol involving several boosters. Thus, this alternative may be useful for producing MAbs against rare or weakly immunogenic cell surface molecules, as suggested by the ease with which we were able to make MAbs against the L3T4-molecule.     

IL-6、CEA、CA19-9和CA72-4对胃癌的诊断价值

探讨血清IL-6、CEA、CA19-9和CA72-4单独或联合检测对胃癌诊断的临床价值。采用电化学发光法分别检测73例胃癌患者（胃癌组）、50例良性胃病患者（良性胃病组）、52名健康者（对照组）血清中IL-6、CEA、CA19-9和CA72-4水平,分析4种指标对胃癌诊断的临床价值及其与临床病理因素之间的关系。在胃癌组,4种标志物血清浓度均显著高于良性胃病组和对照组,并且与肿瘤的组织学分型、浸润深度、淋巴结转移以及远端转移相关。4种标志物平行法联合检测可使诊断的灵敏度提高至86.3%,系列法联合检测可使特异性提高至98.1%。血清IL-6、CEA、CA19-9和CA72-4水平对胃癌的诊断和临床分期具有重要意义,联合检测可提高诊断灵敏度和特异性。