BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening program...BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.展开更多
Hepatitis C virus(HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma(HCC), one of the most common fatal c...Hepatitis C virus(HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma(HCC), one of the most common fatal cancers worldwide- fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M(SCCA-Ig M), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-Ig M may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology.展开更多
BACKGROUND Squamous cell carcinoma antigen(SCCA)is regarded as a specific indicator of epithelial malignancies and is widely used in the diagnosis of squamous cell carcinoma(SCC).However,the expression of SCCA in gast...BACKGROUND Squamous cell carcinoma antigen(SCCA)is regarded as a specific indicator of epithelial malignancies and is widely used in the diagnosis of squamous cell carcinoma(SCC).However,the expression of SCCA in gastric adenocarcinoma has not been studied in detail.CASE SUMMARY A 52-year-old man was admitted to our hospital for a 2.5 cm x 2.5 cm ulcer at the antrum-body junction with dull pain and fullness in the upper abdomen for 2 mo.His pre-surgery serological testing results showed 0.51 ng/mL SCCA(reference interval,<1.5 ng/mL)and 9.9 ng/mL carcinoembryonic antigen(reference range,<4.7 ng/mL).He underwent radical distal gastrectomy and Roux-en Y anastomosis and was diagnosed with poorly differentiated mucinous adenocarcinoma(Lauren classification:Diffuse)by pathological examination of the resected lesion.Immunohistochemistry showed that SCCA was highly expressed in the cytoplasm of cancer cells.After surgery,the patient received an S-1 adjuvant chemotherapy regimen for six cycles containing tegafur,gimeracil,and oteracil potassium.He showed no sign of recurrence or metastasis within 24-mo follow-up.CONCLUSION This is a frontal report of SCCA overexpression in poorly differentiated adenocarcinoma of the stomach.展开更多
<b>Background:</b> Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefu...<b>Background:</b> Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefulness of serum tumor markers for lung squamous cell carcinoma (SQ). We aimed to examine the significance of serum tumor markers for lung SQ. <b>Methods:</b> Eighty-five lung SQ patients who underwent surgery and followed more than 5-year were included. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors, including tumor markers, were compared. We also compared the clinicopathologic factors between central type and peripheral type SQ. <b>Results:</b> The majority of patients were male gender and current/ former smokers. Age, pN status, cytokeratin-19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and comorbid interstitial pneumonia (IP) were associated with the ratio of 5-year survivors significantly. When patients were compared based on tumor location, high p-stage and CYFRA 21-1 were related to central type SQ. <b>Conclusion:</b> Both SCC and CYFRA 21-1 appeared to be useful prognostic markers for patients with lung SQ. Furthermore, CYFRA 21-1 was related to central type SQ.展开更多
Objective: To determine if an amniotic fluid (AF)-specific marker is present and if its concentration changes with the presence of labor. Study Design: Twenty-six healthy women who gave birth to healthy newborns at te...Objective: To determine if an amniotic fluid (AF)-specific marker is present and if its concentration changes with the presence of labor. Study Design: Twenty-six healthy women who gave birth to healthy newborns at term during the period from July 2009 to January 2010 were included in the study. Six candidate markers were assessed by commercially available ELISA kits: interleukin (IL)-6, squamous cell carcinoma (SCC) antigen, insulin-like growth factor (IGFBP)-1, osteopontin (OPN), CA125, and sialyl Tn (STN). Results: The AF/maternal serum (MS) measurement based on IL-6 or SCC has proved to be superior to IGFBP-1, CA125, OPN and STN. Women with spontaneous labor at term had significantly higher IL-6 and IGFBP-1 concentrations in AF compared with those without labor. No significant differences were observed in the AF concentrations of SCC, OPN, CA125 and STN between women with labor and those not in labor. Conclusion: Our observation of IL-6 and SCC in AF may open a new area of research to assess their usefulness as biological markers of obstetrical disorders.展开更多
Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective t...Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets.Dysregulated ribonucleotide reductase(RNR)expression has been confirmed to be causally linked to tumorigenesis.This study demonstrated that ribonucleotide reductase small subunit M2(RRM2)is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes.Mechanistically,HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine(AU)-rich elements(AREs)within the 3′UTR,resulting in persistent overexpression of RRM2.Furthermore,bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis.Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65,R97,I103,and R153 residues,resulting in reduced RRM2 expression.Furthermore,bifonazole exhibited antitumor effects on ESCC patient-derived xenograft(PDX)models by decreasing RRM2 expression and the dNTP pool.In summary,this study reveals the interaction network among HuR,RRM2,and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.展开更多
Background Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clin...Background Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis. Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P=0.001 and P=0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P=-0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P=0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P=0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P=0.007). Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.展开更多
Objective:To clarify whether the serum squamous cell carcinoma antigen(SCCA)levels of patients with inverted papilloma(IP)are different from patients with nasal polyps(NP)and rhinitis.Materials and methods:Serum SCCA ...Objective:To clarify whether the serum squamous cell carcinoma antigen(SCCA)levels of patients with inverted papilloma(IP)are different from patients with nasal polyps(NP)and rhinitis.Materials and methods:Serum SCCA levels were measured in 30 patients with IP and 30 patients with NP at one day before surgery and seven days after surgery and measured in 28 patients with rhinitis.Results:Elevated serum SCCA levels(>1.5 ng/ml)were found in 80.0%of patients in the IP group,6.7%of patients in the NP group and 14.3%of patients in the rhinitis group,which was a significant difference.The medians of serum SCCA levels in the IP,NP and rhinitis groups were 3.9,0.8 and 1.1 ng/ml,respectively,which was a significant difference.The SCCA level in IP group was not significantly correlated according to Krouse Staging.There was a significant difference in serum SCCA levels between the pre-and postoperative stages in the IP group,at 3.9 and 0.8 ng/ml,respectively,while in the NP group the levels were 0.8 and 1.0 ng/ml,not significantly different.With regard to the IP diagnosis in the IP and NP group based on the SCCA level(>1.5 ng/ml),sensitivity and specificity was 80.0%and 93.3%,respectively.Conclusions:The serum SCCA level in patients with IP was elevated and then it decreased after surgery.This was different from NP and rhinitis patients who mostly had normal levels,which did not change.展开更多
基金Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos Ⅲ to support ángela Rojas postdoctoral contract,Consejería de Salud y Familias,Junta de Andalucía supporting Antonio Gil-Gómez contract,PI19/01404 Grant from Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,PI19/00589/Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,and the Xeptagen,Italy,provided the ELISA kits for the measurements of SCCA-IgM.
文摘BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
文摘Hepatitis C virus(HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma(HCC), one of the most common fatal cancers worldwide- fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M(SCCA-Ig M), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-Ig M may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology.
基金The Six Top Talent Project of Jiangsu Province,No.WSW-004National Natural Science Foundation of China,No.81671836and Key Laboratory for Laboratory Medicine of Jiangsu Province of China,No.ZDXKB2016005.
文摘BACKGROUND Squamous cell carcinoma antigen(SCCA)is regarded as a specific indicator of epithelial malignancies and is widely used in the diagnosis of squamous cell carcinoma(SCC).However,the expression of SCCA in gastric adenocarcinoma has not been studied in detail.CASE SUMMARY A 52-year-old man was admitted to our hospital for a 2.5 cm x 2.5 cm ulcer at the antrum-body junction with dull pain and fullness in the upper abdomen for 2 mo.His pre-surgery serological testing results showed 0.51 ng/mL SCCA(reference interval,<1.5 ng/mL)and 9.9 ng/mL carcinoembryonic antigen(reference range,<4.7 ng/mL).He underwent radical distal gastrectomy and Roux-en Y anastomosis and was diagnosed with poorly differentiated mucinous adenocarcinoma(Lauren classification:Diffuse)by pathological examination of the resected lesion.Immunohistochemistry showed that SCCA was highly expressed in the cytoplasm of cancer cells.After surgery,the patient received an S-1 adjuvant chemotherapy regimen for six cycles containing tegafur,gimeracil,and oteracil potassium.He showed no sign of recurrence or metastasis within 24-mo follow-up.CONCLUSION This is a frontal report of SCCA overexpression in poorly differentiated adenocarcinoma of the stomach.
文摘<b>Background:</b> Several previous researchers have investigated the prognostic value of serum tumor markers, especially carcinoembryonic antigen (CEA). Only a limited number of studies reported the usefulness of serum tumor markers for lung squamous cell carcinoma (SQ). We aimed to examine the significance of serum tumor markers for lung SQ. <b>Methods:</b> Eighty-five lung SQ patients who underwent surgery and followed more than 5-year were included. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors, including tumor markers, were compared. We also compared the clinicopathologic factors between central type and peripheral type SQ. <b>Results:</b> The majority of patients were male gender and current/ former smokers. Age, pN status, cytokeratin-19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC), and comorbid interstitial pneumonia (IP) were associated with the ratio of 5-year survivors significantly. When patients were compared based on tumor location, high p-stage and CYFRA 21-1 were related to central type SQ. <b>Conclusion:</b> Both SCC and CYFRA 21-1 appeared to be useful prognostic markers for patients with lung SQ. Furthermore, CYFRA 21-1 was related to central type SQ.
文摘Objective: To determine if an amniotic fluid (AF)-specific marker is present and if its concentration changes with the presence of labor. Study Design: Twenty-six healthy women who gave birth to healthy newborns at term during the period from July 2009 to January 2010 were included in the study. Six candidate markers were assessed by commercially available ELISA kits: interleukin (IL)-6, squamous cell carcinoma (SCC) antigen, insulin-like growth factor (IGFBP)-1, osteopontin (OPN), CA125, and sialyl Tn (STN). Results: The AF/maternal serum (MS) measurement based on IL-6 or SCC has proved to be superior to IGFBP-1, CA125, OPN and STN. Women with spontaneous labor at term had significantly higher IL-6 and IGFBP-1 concentrations in AF compared with those without labor. No significant differences were observed in the AF concentrations of SCC, OPN, CA125 and STN between women with labor and those not in labor. Conclusion: Our observation of IL-6 and SCC in AF may open a new area of research to assess their usefulness as biological markers of obstetrical disorders.
基金funded by National Natural Science Foundation of China(grant numbers:81872335,82303891 and 82303119)The Central Plains Science and Technology Innovation Leading Talents(No.224200510015,China)+1 种基金Key scientific research project plan of colleges and universities in Henan Province(grant number:24A310025,China)Science and Technology Project of Henan Province(No.242102310414,China).
文摘Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets.Dysregulated ribonucleotide reductase(RNR)expression has been confirmed to be causally linked to tumorigenesis.This study demonstrated that ribonucleotide reductase small subunit M2(RRM2)is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes.Mechanistically,HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine(AU)-rich elements(AREs)within the 3′UTR,resulting in persistent overexpression of RRM2.Furthermore,bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis.Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65,R97,I103,and R153 residues,resulting in reduced RRM2 expression.Furthermore,bifonazole exhibited antitumor effects on ESCC patient-derived xenograft(PDX)models by decreasing RRM2 expression and the dNTP pool.In summary,this study reveals the interaction network among HuR,RRM2,and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.
文摘Background Patients with esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (CRT) seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival (OS) was estimated by univariate and multivariate analysis. Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment (P=0.001 and P=0.023, respectively). It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location (P=-0.041). By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 (P=0.002). The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels (P=0.001). In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS (P=0.007). Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.
文摘Objective:To clarify whether the serum squamous cell carcinoma antigen(SCCA)levels of patients with inverted papilloma(IP)are different from patients with nasal polyps(NP)and rhinitis.Materials and methods:Serum SCCA levels were measured in 30 patients with IP and 30 patients with NP at one day before surgery and seven days after surgery and measured in 28 patients with rhinitis.Results:Elevated serum SCCA levels(>1.5 ng/ml)were found in 80.0%of patients in the IP group,6.7%of patients in the NP group and 14.3%of patients in the rhinitis group,which was a significant difference.The medians of serum SCCA levels in the IP,NP and rhinitis groups were 3.9,0.8 and 1.1 ng/ml,respectively,which was a significant difference.The SCCA level in IP group was not significantly correlated according to Krouse Staging.There was a significant difference in serum SCCA levels between the pre-and postoperative stages in the IP group,at 3.9 and 0.8 ng/ml,respectively,while in the NP group the levels were 0.8 and 1.0 ng/ml,not significantly different.With regard to the IP diagnosis in the IP and NP group based on the SCCA level(>1.5 ng/ml),sensitivity and specificity was 80.0%and 93.3%,respectively.Conclusions:The serum SCCA level in patients with IP was elevated and then it decreased after surgery.This was different from NP and rhinitis patients who mostly had normal levels,which did not change.