Risk factors for intraocular metastasis of primary liver cancer in diabetic patients:Alpha-fetoprotein and cancer antigen 125

BACKGROUND In rare instances,primary liver cancer can be associated with intraocular metastasis(IOM).AIM To investigate the correlation between a diverse range of clinical characteristics and IOM in diabetic patients with primary liver cancer,and to determine potential risk factors in predicting IOM.METHODS We recruited a total of 722 diabetic patients with primary liver cancer.The differences between the IOM and non-intraocular metastasis(NIOM)groups in these patients were assessed using the chi-squared test and Student’s t-test.Binary logistic regression analysis was subsequently used to determine risk factors.Finally,the diagnostic value of IOM in this cohort with primary liver cancer was analyzed by receiver operating characteristic(ROC)curve analysis.RESULTS In all,13 patients had IOM.There were no remarkable intergroup differences with respect to age,sex,histopathological sub-types,or blood biochemical parameters.However,the IOM group had significantly higher alpha-fetoprotein(AFP)and cancer antigen 125(CA125)values than the NIOM group.Binary logistic regression identified AFP and CA125 to be significant risk factors for IOM in diabetic patients with primary liver cancer.ROC curve analysis showed that the area under the curve values for AFP and CA125 were 0.727 and 0.796,with the cut-off values of 994.20 ng/mL and 120.23 U/mL,respectively.The sensitivity and speci
city for AFP were 92.3%and 59.9%,while those for CA125 were 84.6%and 70.1%,respectively.CONCLUSION Elevated AFP and CA125 represent significant risk factors for IOM in diabetic patients with primary liver cancer.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers

BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.

Prostate cancer antigen-1 as a cancer potential novel marker for prostate

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.

Expression and significance of carcinoembryonic antigen, cancer antigen 153, and cyclooxygenase-2 in breast cancer

Objective This study aimed to evaluate serum and nipple discharge levels of carcinoembryonic antigen(CEA) and cancer antigen 153(CA153) and tissue cyclooxygenase-2(COX-2) expression in breast cancer cases and associations of these proteins with breast cancer metastasis.Methods The immunohistochemical Ultra Sensitive^(TM) S-P method was used to detect COX-2 expression in 77 cases of invasive breast carcinoma. Of these cases, 52 exhibited CEA and CA153 in both serum and nipple discharge(electrochemiluminescence method), and associations of these biomarkers with breast cancer prognosis were studied. Sixty cases of benign breast lesion were selected as a control group. Overall survival of breast carcinoma patients was evaluated. COX-2 expression was evaluated relative to clinicopathological features and CEA and CA153 levels, and its role in invasiveness was investigated.Results Among cases of invasive breast cancer, 72.7%(56/77) were COX-2 immunopositive, compared to 16.7% of benign lesions(χ2 = 66.745, P = 0.000) percentage of positive cells. COX-2 overexpression in breast cancer correlated positively with histological grade(II vs III; χ2 = 4.064, P = 0.043), lymph node metastasis(χ2 = 9.135, P = 0.003), and distant metastasis(χ2 = 8.021, P = 0.003). However, COX-2 expression did not correlate with age(≤ 50 vs 50 years) or tumor size(≤ 5 vs > 5 cm)(χ2 = 0.081, P = 0.776 and χ2 = 3.702, P = 0.054, respectively). Among breast cancer patients, COX-2 overexpression in tumors also correlated with shorter overall survival(P < 0.05). In brief, increased COX-2 expression correlates with worse prognosis and shorter overall survival. Malignant lesions were associated with significantly higher serum and nipple discharge levels of biomarkers, relative to benign lesions(P < 0.05). These biomarkers were present at significantly higher levels in nipple discharge than in serum(P < 0.05). Furthermore, significantly higher nipple discharge levels of CEA and CA153 were observed in COX-2-positive breast carcinoma patients, compared to COX-2-negative patients(P <0.05). Shorter overall survival in cancer patients group related to COX-2 overexpression in tumors(P < 0.05).Conclusion The study suggests that COX-2 overexpression correlates with poor clinicopathological parameters in breast cancers and might be an important biological marker of invasion and metastasis. The findings of the present study suggest that combined detection of COX-2 tissue expression and CEA and CA153 in serum and nipple discharge could facilitate clinical monitoring and diagnosis of metastasis in patients with breast cancer.

Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

AIM: To investigate the effects of our tumor vaccines on reversing immune tolerance and generating therapeutic response.METHODS: Vaccines were synthesized by solid phase using an Fmoc strategy,where a small molecule toll-like receptor-7 agonist(T7) was conjugated to a monoclonal gastric cancer 7 antigen mono-epitope(T7-MG1) or tri-epitope(T7-MG3).Cytokines were measured in both mouse bone marrow dendritic cells and mouse spleen lymphocytes after exposed to the vaccines.BALB/c mice were intraperitoneally immunized with the vaccines every 2 wk for a total of three times,andthen subcutaneously challenged with Ehrlich ascites carcinoma(EAC) cells.Three weeks later,the mice were killed,and the tumors were surgically removed and weighed.Serum samples were collected from the mice,and antibody titers were determined by ELISA using an alkaline phosphate-conjugated detection antibody for total Ig G.Antibody-dependent cell-mediated cytotoxicity was detected by the lactate dehydrogenase method using natural killer cells as effectors and antibody-labeled EAC cells as targets.Cytotoxic T lymphocyte activities were also detected by the lactate dehydrogenase method using lymphocytes as effectors and EAC cells as targets.RESULTS: Vaccines were successfully synthesized and validated by analytical high performance liquid chromatography and electrospray mass spectrometry,including T7,T7-MG1,and T7-MG3.Rapid inductions of tumor necrosis factor-α and interleukin-12 in bone marrow dendritic cells and interferon γ and interleukin-12 in lymphocytes occurred in vitro after T7,T7-MG1,and T7-MG3 treatment.Immunization with T7-MG3 reduced the EAC tumor burden in BALB/c mice to 62.64% ± 5.55% compared with PBS control(P < 0.01).Six or nine weeks after the first immunization,the monoclonal gastric cancer 7 antigen antibody increased significantly in the T7-MG3 group compared with the PBS control(P < 0.01).As for antibody-dependent cell-mediated cytotoxicity,antisera obtained by immunization with T7-MG3 were able to markedly enhance cell lysis compared to PBS control(31.58% ± 2.94% vs 18.02% ± 2.26%; P < 0.01).As for cytotoxic T lymphocytes,T7-MG3 exhibited obviously greater cytotoxicity compared with PBS control(40.92% ± 4.38% vs 16.29% ± 1.90%; P < 0.01).CONCLUSION: A successful method is confirmed for the design of gastric cancer vaccines by chemical conjugation of T7 and multi-repeat-epitope of monoclonal gastric cancer 7 antigen.

Improved detection Of the MUC1 cancer antigen CA 15-3 by ALYGNSA fluorimmunoassay

Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed;this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy

Prostate cancer antigen 3 （PCA3） is a biomarker for diagnosing prostate cancer （PCa） identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic （ROC） curve （AUC） and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA （0.750 vs 0.622, P = 0.046） in patients with a PSA of 4.0-10.0 ng ml-I, but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1. However, the AUC of the PCA3 score （0.712） is not superior to %fPSA （0.698） or PSAD （0.773） in patients with a PSA 〉10.0 ng ml-1. Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1.

Prostate cancer antigen 3 test for prostate biopsy decision： a systematic review and meta analysis

Background The specificity for early interventions of prostate-specific antigen （PSA） in prostate cancer （PCa） is not satisfactory.It is likely that prostate cancer antigen 3 （PCA3） can be used to predict biopsy outcomes more accurately than PSA for the early detection of PCa.We systematically reviewed literatures and subsequently performed a meta-analysis.Methods A bibliographic search in the database of Embase,Medline,Web of Science,NCBI,PubMed,CNKI,and those of health technology assessment agencies published before April 2013 was conducted.The key words used were ＂prostatic neoplasms＂,＂prostate＂,＂‘prostate,＇ ‘carcinoma＇ or ‘cancer＇ or ‘tumor＇,or ‘PCa,＇＂ and free terms of ＂upm3＂,＂pca3＂,＂dd3＂,＂aptimapca 3＂,and ＂prostate cancer antigen 3＂.All patients were adults.The intervention was detecting PCA3 in urine samples for PCa diagnosis.We checked the quality based on the QUADAS criteria,collected data,and developed a meta-analysis to synthesize results.Twenty-four studies of diagnostic tests with moderate to high quality were selected.Results The sensitivity was between 46.9％ and 82.3％; specificity was from 55％ to 92％; positive predictive value had a range of 39.0％-86.0％; and the negative predictive value was 61.0％-89.7％.The meta-analysis has heterogeneity between studies.The global sensitivity value was 0.82 （95％ Cl 0.72-0.90）; specificity was 0.962 （95％ Cl 0.73-0.99）; positive likelihood ratio was 2.39 （95％ Cl 2.10-2.71）; negative likelihood ratio was 0.51 （95％ Cl 0.46-0.86）; diagnostic odds ratio was 4.89 （95％ Cl 3.94-6.06）; and AUC in SROC curve was 0.744 1.Conclusion PCA3 can be used for early diagnosis of PCa and to avoid unnecessary biopsies.

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.

Cancer/testis antigens： novel tools for discerning aggressive and non-aggressive prostate cancer

The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.

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.

Value of ^(18)F-FDG PET-CT in surveillance of postoperative colorectal cancer patients with various carcinoembryonic antigen concentrations

AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)concentrations.METHODS:One hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose(FDG)PET/CT within one week were included in this study.The final diagnosis was confirmed by histological examination or clinicalfollow-up over at least six months.RESULTS:The sensitivity,specificity,and accuracy of FDG PET/CT were 95.2%,82.6%,and 92.5%,and94.8%,81.4%and 92.8%,respectively,in the caseand lesion-based analyses.The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses(χ2=8.186,P=0.004;χ2=6.201,P=0.013;χ2=13.445,P=0.000;χ2=11.194,P=0.001).In the lesion-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT in the abnormal CEA group were97.8%,82.6%,and 95.6%,compared with 81.3%,80%,and 80.6%for patients with normal CEA levels.In case-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT were 97.2%,77.8%,and 95%in abnormal CEA group.Only in lesion-based analysis,the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group(χ2=6.432,P=0.011;χ2=7.837,P=0.005).FDG PET/CT changed the management in 45.8%of patients with positive scans.CONCLUSION:FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.

Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection

AIM:To determine whether serum levels of carcinoembryonic antigen(CEA) correlate with the presence of primary colorectal cancer(CRC),and/or recurrent CRC following radical resection.METHODS:A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study.The median follow-up period was 69 mo(range,3-118 mo),and CRC recurrence was experienced by 90/413(21.8%) patients.Serum levels of CEA were assayed preoperatively,and using a cutoff value of 5 ng/mL,patients were divided into two groups,those with normal serum CEA levels(e.g.,≤ 5 ng/mL) and those with elevated CEA levels(> 5 ng/mL).RESULTS:The overall sensitivity of CEA for the detection of primary CRC was 37.0%.The sensitivity of CEA according to stage,was 21.4%,38.9%,and 41.7% for stagesⅠ-Ⅲ,respectively.Moreover,for stageⅡandstageⅢcases,the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels(P < 0.05).The overall sensitivity of CEA for detecting recurrent CRC was 54.4%,and sensitivity rates of 36.6%,66.7%,and 75.0% were associated with cases of local recurrence,single metastasis,and multiple metastases,respectively.In patients with normal serum levels of CEA preoperatively,the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection(32.6% vs 77.3%,respectively,P < 0.05).CONCLUSION:CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence,especially in cases of local recurrence vs cases of metastasis.

High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer

AIM:To assess the clinical significance and the prognostic value of preoperative serum carbohydrate antigen 19-9(CA 19-9)level in gastric cancer.METHODS:Between January 2005 and December2006,1960 patients underwent surgery for histologically confirmed gastric cancer.Of these,163 patients had elevated serum levels of CA 19-9 preoperatively,and1628 patients had normal serum levels of CA 19-9 preoperatively.For this study,325 patients were selected from the group of 1628 patients by age,sex,and cancer stage to serve as controls.Statistically significant differences in survival rates were calculated using the log-rank test.A P value less than 0.05 was considered statistically significant and was determined using SAS software.RESULTS:The baseline characteristics showed some differences between the two groups with regard to histology.Overall survival(OS)in the elevated and nonelevated group was 37.90 and 68.67 mo,respectively(P<0.001).N stage(P=0.001)was a significant predictor of disease-free survival by multivariate analysis.Also,N stage(P<0.001),and the presence of peritoneal metastasis(P<0.001)remained independent factors in predicting OS by multivariate analysis.Additionally,preoperative serum CA 19-9 levels were significantly associated with OS in univariate(P=0.009)and multivariate(P=0.021)analyses.CONCLUSION:Serum CA 19-9 can be considered an independent prognostic factor in predicting OS in patients anticipating surgery for gastric cancer.

Chimeric antigen receptor-engineered T-cell therapy for liver cancer

Background: Chimeric antigen receptor-engineered T-cell(CAR-T) therapy is a newly developed immunotherapy used in the treatment of cancers. Because CAR-T therapy has shown great success in treating CD19-positive hematological malignancies, its application has been explored in the treatment of solid tumors, such as liver cancer. In this review, we discuss the immune characteristics of liver cancer, the obstacles encountered during the application of CAR-T therapy, and preclinical and clinical progress in the use of CAR-T therapy in patients with liver cancer.Data sources: The data on CAR-T therapy related to liver cancers were collected by searching Pub Med and the Web of Science databases prior to December 2017 with the keywords "chimeric antigen receptor","CAR-T", "liver cancer", "hepatocellular carcinoma", and "solid tumor". Additional articles were identified by manual search of references found in the primary articles. The data for clinical trials were collected by searching Clinical Trials.gov.Results: The liver has a tolerogenic nature in the intrahepatic milieu and its tumor microenvironment significantly affects tumor progression. The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment. To overcome these obstacles, several strategies have emerged. In addition, several strategies have been developed to manage the side effects of CAR-T, including enhancing the selectivity of CARs and controlling CAR-T activity. To date, no clinical trials of CAR-T therapy against HCC have been completed. However, preclinical studies in vitro and in vivo have shown potent antitumor efficacy. Glypican-3, mucin-1, epithelial cell adhesion molecule, carcinoembryonic antigen, and other targets are currently being studied.Conclusions: The application of CAR-T therapy for liver cancer is just beginning to be explored and more research is needed. However, we are optimistic that CAR-T therapy will offer a new approach for the treatment of liver cancers in the future.

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.

Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression:A Hypothesis

Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

Inhibition of host immune response in colorectal cancer:Human leukocyte antigen-G and beyond

Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class&#x02005;I&#x02005;human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.