Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients

AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP) in these patients was also determined.RESULTS:The positive rate of MAGE-1,SSX-1 and CTp11 transcripts was 37.7%,34.4%,31.1% in PBMC samples,and 74.4%,73.3%,62.2% in their resected tumor samples,respectively.The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples.MAGE-1,SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1,SSX-1 and/or CTp11 mRNA negative,nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients.Among the 90 patients,the serum AFP in 44 patients met the general diagnostic standard(AFP > 400 μg/L) for HCC,and was negative(AFP ≤ 20 μg/L) or positive with a low concentration(20 μg/L < AFP ≤ 400 μg/L) in the other patients.The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%,respectively.Of the 90 patients,71(78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP.Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage or was obviously higher than that in PBMC samples from 37 patients at stage or(77.9% vs 51.4%,P = 0.010),the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages andrespectively.CONCLUSION:Detecting MAGE-1,SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.

Early gastric cancer frequently has high expression of KKLC-1, a cancer-testis antigen

AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

Expression of Cancer-testis Antigen in Multiple Myeloma

Recently, the immunotherapy has been highlighted among cancer treatments. Cancer-testis antigen （CTA） has been studied in a variety of solid tumors because of its specific expression in tumors, and testis, ovary and placenta tissues, but not in other normal tissues. In order to provide a new ap- proach for multiple myeloma （MM） immunotherapy, we examined the CTA expression in MM cell lines, and primary myeloma cells in patients with MM. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in MM cell lines of RPMI-8226 and U266, and bone marrow （BM） Cells of 25 MM patients and 18 healthy vol- unteers. The results showed that the 4 CTAs were expressed in RPMI-8226 and U266 cell lines. The positive expression rate of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in the BM cells of 25 MM patients was 28% （7/25）, 80% （20/25）, 40% （10/25） and 68% （17/25）, respectively. In contrast, the expression of any member of the CTAs was not detected in BM cells of 18 healthy volunteers. The expression of two or more CTAs was detected in 80% （20/25） MM patients, and that of at least one CTA in 88% （22/25）. The mRNA expression levels of SSX1 and SSX4 were significantly higher in patients with MM at stage III than in those at stage I and II （P〈0.05）. No statistically significant differences were observed in the mRNA expression levels of MAGE-C 1/CT7 and SSX2 in further stratified analyses by age, gender, MM types and percentage of MM cells in BM （P〉0.05）. In conclusion, our present study showed that MAGE-C1/CT7, SSX1, SSX2 and SSX4 were co-expressed in MM cell lines and the primary myeloma cells in MM patients, but not expressed in BM cells of healthy subjects. The mRNA levels of SSX1 and SSX4 are associated with MM clinical stage. This work may provide a new insight into MM immuno- therapy in the future.

Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma

Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

Prostate cancer with elevated free prostate-specific antigen density:A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide,and prostate-specific antigen(PSA)is often used in clinical practice to screen for prostate cancer.Normal total PSA(tPSA)level initially excludes prostate cancer.Here,we report a case of prostate cancer with elevated free PSA density(fPSAD).CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy,and the postoperative pathological results showed acinar adenocarcinoma of the prostate.The patient is currently undergoing endocrine chemotherapy.CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

Antigen epitopes of animal coronaviruses:a mini-review

Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.

Prevalence and Factors Associated with Positivity of Antinuclear Antibodies (ANA) Patterns, Native Anti-DNA and Extractable Nuclear Antigens (ENA) Antibodies: Experience from a Laboratory in Dakar

Background: Diagnosis of autoimmune diseases (AID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA) are sensitive screening tests but anti-deoxyribonucleic acid-antibody (anti-DNA), and anti-extractable nuclear antigens (anti-ENA) are specific for AIDs. We aimed to look at ANA patterns in our patients and correlated them with anti-ENA for proper interpretation and better patient management cost-effectively. Methods: A retrospective study was conducted over 1 year from January to December 2022 who were tested for ANA at biology medical laboratory of Pasteur Institute of Dakar. Anti-ENA and anti-DNA results were also analyzed for ANA-positive patients. Statistical analysis was performed using STATA 14.0, p Results: 216 patients were analyzed. Women predominated at 79.2% and mean age was 48 years [CI 95%, 46 - 50], with extremes of 10 and 89. Most represented age group was [41 - 60] with 38%. ANA was positive in 27 (12.5%) of patients, 59.2% of whom were strongly positive (titer of 1/1000, 1/3200 or 1/6400). The most common pattern was nuclear speckled, which was found in 77.8% of samples. Anti-ENA and anti-DNA positivity in ANA-positive patients was found respectively in 63% (17/27) and 1.4% (3/27) of the samples analyzed. Most commonly identified anti-ENA was anti-Sm 29.6%, anti-SSA 29.6%, anti-Ro-52 25.9%, anti-RNP 18.5% and anti-SSB 14.8% which was associated with speckled pattern. Association results indicated a significant relationship between both tests and between ANA titer in the anti-ENA- and ANA-positive patients (p 0.001). Conclusions: ANA, Anti-ENA and anti-DNA antibodies are essential for AIDS diagnosis. However, the testing repertoire should follow an algorithm comprising of clinical features, followed by ANA results with nuclear, mitotic, and cytoplasmic patterns, anti-ENA, and anti-DNA for a more meaningful, and cost-effective diagnostic approach.

Carcinoembryonic antigen in the diagnosis,treatment,and follow-up of focal liver lesions

In this editorial review,we comment on the article published in the recent issue of the World Journal of Gastrointestinal Surgery.Carcinoembryonic antigen(CEA)is a fetal glycoprotein and can be secreted in very small amounts from healthy adults after birth.CEA is widely used not only for diagnostic tumor markers but also importantly for the management of some gastrointestinal tumors.The most common clinical use is surveillance for the monitoring of colorectal carcinoma.However,CEA can become elevated in several malign or benign characterized pathologies.Serum CEA level may vary depending on the location of the lesion,whether it metastasizes or not,and its histopathological characteristics.It has been determined that cases with high preoperative CEA have a more aggressive course and the risk of metastasis to the lymph tissue and liver increases.In this editorial review,we focused on evaluating the role of CEA in clinical practice with a holistic approach,including the diagnostic and prognostic significance of CEA in patients with focal liver lesions,the role of CEA in follow-up after definitive surgery,and also hepatic resection for metastasis,and the management of all patients with raised CEA.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.

Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells in the complex milieu of the liver.In this section,we will comment on the importance of donorspecific anti-human leukocyte antigen(HLA)antibodies(DSA)as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor(KIR)genotypes in the evolution of liver transplantation.Thus,HLA compatibility,viral infections,and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival.There have been reports of increased risk of acute and chronic rejection with ductopenia,faster graft fibrosis,biliary problems,poorer survival,and even de novo autoimmune hepatitis when DSAs are present in the recipient.Higher mean fluorescence intensity(MFI)values of the DSAs and smaller graft size were associated with poorer patient outcomes,implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods,according to the investigators.Similarly,in a combined kidney-liver transplant,a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment.The renal graft was lost owing to antibody-mediated rejection(AMR).The HLA antigens expressed by the transplanted liver graft influenced antibody elimination.Pathologists are increasingly diagnosing AMR in liver transplants,and desensitization therapy has even been employed in situations of AMR,particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex.In conclusion,after revealing the negative impacts of DSAs with high MFI,pretransplant virtual crossmatch techniques may be appropriate to improve evolution;however,they may extend cold ischemia periods by requiring the donor to be typed.

Carcinoembryonic antigen,carbohydrate antigen 199 and carbohydrate antigen 724 in gastric cancer and their relationship with clinical prognosis

BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

Tumor neoantigens: Novel strategies for application of cancer immunotherapy

Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.

Immune responses of six-transmembrane epithelial antigen of the prostate 4 functions as a novel biomarker in gastric cancer

BACKGROUND Immune cells play an important role in regulating the behavior of tumor cells.According to emerging evidence,six-transmembrane epithelial antigen of the prostate 4(STEAP4)performs a crucial part in tumor microenvironmental immune response and tumorigenesis,and serves as the potential target for cellular and antibody immunotherapy.However,the immunotherapeutic role of STEAP4 in gastric cancer(GC)remains unclear.AIM To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells,and explore the potential value of STEAP4 as an immune prognostic indicator in GC.METHODS The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients.Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature.R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC(GSE62254)by the ESTIMATE algorithm,and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis.RESULTS Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues,and STEAP4 expression was positively correlated with the clinical stage of GC.In GC,the expression of STEAP4 was positively correlated with the infiltration levels of B cells,CD4+T cells,macrophages,neutrophils,and dendritic cells.The expression level of STEAP4 was strongly correlated with most of the immune markers.In addition,STEAP4 expression was inversely correlated with tumor purity,but correlated with stromal score(r=0.43,P<0.001),immune score(r=0.29,P<0.001)and estimate score(r=0.39,P<0.001).Moreover,stromal,immune,and estimate scores were higher in the STEAP4 high expression group,whereas tumor purity was higher in the STEAP4 Low expression group.The relationship between STEAP4 expression and prognosis of patients with GC was further investigated,and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival.In addition,Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC.CONCLUSION The current findings suggest an oncogenic role for STEAP4 in GC,with significantly high levels being associated with poor prognosis.Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells,which may contribute to the regulation of the tumor microenvironment.In conclusion,STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration,as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.

Expression and Evaluation of Wb-SXP-1 and Wb-123 Recombinant Antigens as Potential Diagnostic Biomarkers for Lymphatic Filariasis

Lymphatic filariasis (LF) remains a public health concern as it can cause permanent morbidity and disability to those infected. While the global elimination of LF in these endemic areas is ongoing through mass drug administration, there is the need to develop diagnostic tools that would be utilized to track the progress of total global eradication as well as perform surveillance for the recurrence of lymphatic filariasis transmission. Currently, approved LF diagnosis tools are faced with lack of specificity, low sensitivity, and periodicity dependence. Recombinant filarial antigen-based assays can address these drawbacks and offer practical instruments for LF diagnosis and surveillance. This present study, evaluated rWb-SXP-1 and rWb-123 antigens as potential diagnostic biomarker tools for Wuchereria banchrofti in human sera using microspheres-based multiplex serological assay. Based on statistical analysis using XLSTAT 2019 (Addinsoft) on data generated from multiplex technology assay, generated ROC curves for both rWb-SXP-1 and rWb-123 demonstrated 87.1% sensitivity to Wuchereria banchrofti human sera with rWb-SXP-1 antigens having the highest specificity of 96%. Indication that rWb-SXP-1 and rWb-123 antigens are capable of detecting immunoglobulin G4 (IgG4) antibodies in human sera synthesized specifically against W. banchrofti infections. Therefore, rWb-SXP-1 and rWb-123 antigens can be utilized to detect W. banchrofti infections by antibody profiling with excellent diagnostic sensitivity and specificity using microsphere-based multiplex serological tests. This method can be particularly practical for screening a large number of sera samples and/or for quick, extensive field-testing due to the high-throughput and quick formats applied.

Association of Haplotypes in Exon 4 of KLK2 Gene with Raised Serum Prostate-Specific Antigen

The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X2 = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.

Contribution of Automated Antigen Tests, the LumiraDx Ag Test in the Response during the Second Wave of the COVID-19 Pandemic in Bangui

Context and objective: The COVID-19 pandemic has become a major public health problem and has mobilized many innovative means of diagnosis. The Central African Republic is not spared. The emergence of variants and their impact require health monitoring despite the obligation of vaccination. The purpose of this campaign was to determine the circulation of pending second-wave variants. Patients and Methods: A second mass screening campaign took place from 02 to 22 July 2021 in the main land and river entry points of Bangui (Exit North-PK12, Exit South-PK9, Port Beach) and at the LNBCSP. Antigenic and RT-PCR tests carried out on nasopharyngeal samples made it possible to select strains which were finally sequenced. Results: Of 2687 participants included in the study, 53 (1.97%) were positive for SARS-CoV-2. Thirteen (1.53%) were male and 40 (2.18%) female. The analyses carried out on the LumiraDx analyzer were positive for 109 samples against 53 on the RT-PCR. The prevalence was higher in the most tested age groups (30 to 50 years) with two clusters identified. B.1.617.2 (Delta) variants were predominant (57%). Conclusion: SARS-CoV-2 continues to circulate. The acquisition of automated antigenic tests (LumiraDx&#174) with sensitivity and specificity close to those of the reference test (RT-PCR) will allow better mass diagnosis for an optimization of the surveillance of COVID-19 in our countries with limited resources. The predominance of the B.1.617.2 (Delta) variant would suggest a third wave in the Central African Republic.

Significance of carcinoembryonic antigen detection in the early diagnosis of colorectal cancer:A systematic review and metaanalysis

BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor involving adenomas that develop into malignant lesions.Carcinoembryonic antigen(CEA)is a non-specific serum biomarker upregulated in CRC.The concentration of CEA is modulated by tumor stage and grade,tumor site in the colon,ploidy status,and patient smoking status.This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.AIM To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.METHODS A systematic search was performed using four databases:MEDLINE,Cochrane Trials,EMBASE,and the Web of Science.The inclusion criteria were as follows:Adult patients aged≥18 years who had completed CRC curative treatment and were followed up postoperatively;reporting the number of CRC recurrences as an outcome;and randomized,clinical,cohort,and case-control study designs.Studies that were not published in English and animal studies were excluded.The following data were extracted by three independent reviewers:Study design,index tests,follow-up,patient characteristics,and primary outcomes.All statistical analyses were performed using the RevMan 5.4.1.RESULTS A total of 3232 studies were identified,with 73 remaining following the elimination of duplicates.After screening on predetermined criteria,12 studies were included in the final analysis.At a reference standard of 5 mg/L,CEA detected only approximately half of recurrent CRCs,with a pooled sensitivity of 59%(range,33%–83%)and sensitivity of 89%(range,58%–97%).CONCLUSION CEA is a significant marker for CRC diagnosis.However,it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence,with an essential proportion of false negatives.