Tumor Markers AFP Research Articles

A case of complete response to radiotherapy combined with durvalumab and tremelimumab in a patient with unknown primary hepatocellular carcinoma arising in the lumbar spine.

A 58-year-old man visited an orthopedic clinic complaining of pain in his right lower back and numbness in his lower limbs for one month. Imaging tests revealed a tumorous lesion from the left side of the second lumbar vertebra to the paraspinal muscles. CT-guided biopsy of the tumor was performed, and immunostaining results diagnosed hepatocellular carcinoma (HCC). Although the liver showed signs of chronic liver damage, no primary tumor was found within the liver or in other organs. Blood tests showed negative hepatitis virus markers for both HBV and HCV. The tumor markers AFP, AFP-L3, and DCP were high. Because he developed spinal cord compression syndrome due to a lumbar tumor, radiation therapy and denosumab administration were performed. Subsequently, systemic therapy with durvalumab plus tremelimumab was started. In the year following the start of treatment, the tumor has shrunk, and no new lesions have been observed. Tumor markers have also decreased. We have experienced a case of HCC in the lumbar spine without a primary tumor in the liver. This is a very rare case, and the combination therapy with durvalumab and tremelimumab resulted in a complete response, which we consider to be a valuable case.

Validity of Prothrombin-induced Vitamin K antagonist versus Alpha-Fetoprotein (Tumor Markers) in Diagnosis of Hepatocellular Carcinoma, Using Computed Tomography scan as Gold Standard

Biomarkers like alpha-fetoprotein and prothrombin-induced Vitamin K deficiency/ antagonist are used in the early diagnosis and staging of hepatocellular carcinoma and are useful for better outcomes in the treatment and overall survival of the patient. Objective: To compare the diagnostic accuracy of alpha-fetoprotein and prothrombin-induced Vitamin K antagonist in the diagnosis of hepatocellular carcinoma using a computed tomography scan as a gold standard. Methods: A cross-sectional study was conducted in the Liver Transplant Unit of Shaikh Zayed Postgraduate Medical Complex, Lahore from July 2023 to January 2024. A total of 94 patients older than 12 years old with cirrhosis and CT scan suggestive of hepatocellular carcinoma were selected. Blood was collected to test for AFP and PIVKA-II. The samples were sent to the labs after labeling them properly and the results were collected and entered in the data sheet. Patients were advised to have a multiphase contrast-enhanced CT scan. Patients were followed up in the clinic after 7 days. Results: The diagnostic accuracy of AFP was 78% with a 74.7% sensitivity, 100% specificity, 100% positive predictive value, and 41.67% negative predictive value. The diagnostic accuracy of PIKVA-II was found to be 87.76% with 89% sensitivity, 80% specificity, 96.1% PPV, and 57.14% NPV. Conclusions: On comparing the tumor markers AFP with PIVKA-II against the gold standard multiphase CT scan it was found that PIVKA-II has better diagnostic accuracy than AFP.

Diagnostic Efficacy of Tumor Markers AFP, CA19-9, and CEA in Hepatocellular Carcinoma Patients

Diagnostic Efficacy of Tumor Markers AFP, CA19-9, and CEA in Hepatocellular Carcinoma Patients

Prognostic value of dynamic changes of pre- and post-operative tumor markers in colorectal cancer.

Colorectal cancer (CRC) prognosis assessment is vital for personalized treatment plans. This study investigates the prognostic value of dynamic changes of tumor markers CEA, CA19-9, CA125, and AFP before and after surgery and constructs prediction models based on these indicators. A retrospective clinical study of 2599 CRC patients who underwent radical surgery was conducted. Patients were randomly divided into training (70%) and validation (30%) datasets. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and nomograms were constructed. A total of 2599 CRC patients were included in the study. Patients were divided into training (70%, n = 1819) and validation (30%, n = 780) sets. Univariate and multivariate Cox regression analyses identified age, total number of resected lymph nodes, T stage, N stage, the preoperative and postoperative changes in the levels of CEA, CA19-9, and CA125 as independent prognostic factors. When their postoperative levels are normal, patients with elevated preoperative levels have significantly worse overall survival. However, when the postoperative levels of CEA/CA19-9/CA125 are elevated, whether their preoperative levels are elevated or not has no significance for prognosis. Two nomogram models were developed, and Model I, which included CEA, CA19-9, and CA125 groups, demonstrated the best performance in both training and validation sets. This study highlights the significant predictive value of dynamic changes in tumor markers CEA, CA19-9, and CA125 before and after CRC surgery. Incorporating these markers into a nomogram prediction model improves prognostic accuracy, enabling clinicians to better assess patients' conditions and develop personalized treatment plans.

Radiomics and Clinicopathological Characteristics for Predicting Lymph Node Metastasis in Testicular Cancer

Accurate prediction of lymph node metastasis (LNM) in patients with testicular cancer is highly relevant for treatment decision-making and prognostic evaluation. Our study aimed to develop and validate clinical radiomics models for individual preoperative prediction of LNM in patients with testicular cancer. We enrolled 91 patients with clinicopathologically confirmed early-stage testicular cancer, with disease confined to the testes. We included five significant clinical risk factors (age, preoperative serum tumour markers AFP and B-HCG, histotype and BMI) to build the clinical model. After segmenting 273 retroperitoneal lymph nodes, we then combined the clinical risk factors and lymph node radiomics features to establish combined predictive models using Random Forest (RF), Light Gradient Boosting Machine (LGBM), Support Vector Machine Classifier (SVC), and K-Nearest Neighbours (KNN). Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the decision curve analysis (DCA) was used to evaluate the clinical usefulness. The Random Forest combined clinical lymph node radiomics model with the highest AUC of 0.95 (±0.03 SD; 95% CI) was considered the candidate model with decision curve analysis, demonstrating its usefulness for preoperative prediction in the clinical setting. Our study has identified reliable and predictive machine learning techniques for predicting lymph node metastasis in early-stage testicular cancer. Identifying the most effective machine learning approaches for predictive analysis based on radiomics integrating clinical risk factors can expand the applicability of radiomics in precision oncology and cancer treatment.

Altered expression of activated induced hepatocellular carcinoma markers (HCCmk) in murine model treated with Portulaca oleracea L.

Hepatocellular carcinoma (HCC) is a wan prognosis and is highly resistant to cancer therapy, pushing the search for safe drugs as an essential issue. Plant-based bioproducts may reduce the negative side effects of cancer treatment. By the present study, we evaluated the ability of a defatted methanol and hexane extracts from Portulaca oleracea to regulate HCC in an animal model. The anticancer activity of Portulaca oleraceae L. (PO) extract was evaluated against HepG2 cell line where IC50 was 241.79 µg/ml for PO MeOH extract and 122.19 µg/ml for PO Hex extract. Overall, treatment with DEN+ PO Hex 200 mg/kg shows 100% survival rate. Furthermore, it improved the preservation of hepatocyte architecture in animals with small hepatocyte alterations but interspersed with foci of hepatocyte apoptosis as well as liver enzymes ALP (11.77±4.02 IU/L), AST (114.15±11.79 IU/L), ALT (22.11±2.66 IU/L) and TBILR (0.4±0.20 IU/L). The relative expression of serum TNF-α was significantly up-regulated in DEN induced HCC mice to reach (322.44±11.2) compared to normal mice (0.07±0.02). Besides the TNF-α in DEN/ PO groups were significantly down-regulated to be (73.98±2.7), so the relative expression level of tumor markers BCl-2 and AFP. In addition, apoptotic markers BAX and Cas-8 were significantly increased in DEN/ P. oleracea treated mice. Chemical profiling of methanol and hexan extracts using GC–MS and HPLC analysis revealed that 9,12,15 octadecatrienoic acid, (2-phenyl-1,3-dioxolan-4-yl) methyl ester, mesitylene, 2-Hydroxy-3-[(9E)-9-octadec-enoylox] propyl(9E) octadecenoate, and 2-(phenymethylene) octanal are the major compounds that were identified by GC_MS analysis of PO Hex extract. While, HPLC clarified the presence of pyrogallol, Syringenic acid, Caffeic acid, P-coumaric acid and Cinnamic acid as major phenolic compounds besides Catechin, Luteolin, and rutin as major flavonoid compounds in PO MeOH extract. Taken together, these results provide the first visualization of the action effects of several compounds in PO and represent potential anti HCC therapy.

Association between serum alpha-fetoproteinlevel and liver function parameters in hepatocellular carcinoma patients: A case-control study

: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer occurs in people with liver diseases like chronic hepatitis B and hepatitis C virus. Early diagnosis and monitoring of HCC is possible with the help of tumor marker AFP. The aim of the study was to assess whether AFP level is associated with selected liver function tests in hepatocellular carcinoma patients.: Total 90 individuals are selected, 50 HCC patients with AFP >20ng/ml and 40 subjects (normal LFT and AFP value <10ng/ml) with an age between 40-70. Serum is used for analysis of AFP, SGOT, SGPT, ALP by Maglumi 1000 and Siemen biochemistry analyzer (using principle Chemiluminescence immunoassay) respectively. Unpaired T test (IBM SPSS 22.0) were used. Elevated levels of AFP (p value <0.05), SGOT (p value < 0.001), SGPT (p value < 0.001), ALP (p value < 0.001) shows statistical significance within study population and also indicated the risk of developing HCC with respect to AFP level in liver disease patients with elevated LFT parameters.: From the study, it is concluded that LFT and AFP are comparatively elevated in HCC. Treatment is usually not possible with advanced HCC due to failure of not doing proper screening at appropriate time. Early diagnosis and monitoring of HCC are possible with the help of tumor marker AFP.

Assessing Epstein–Barr virus in gastric cancer: clinicopathological features and prognostic implications

BackgroundEpstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) was a unique molecular subtype of gastric cancer (GC). However, the clinicopathological characteristics and prognostic role of EBV infection remains unclear. We aimed to evaluate the clinicopathological features of EBVaGC and its role on prognosis.MethodsEBV-encoded RNA (EBER) in situ hybridization method was used to evaluate the EBV status in GC. The serum tumor markers AFP, CEA, CA19-9 and CA125 of patients were detected before treatment. HER2 expression and microsatellite instability (MSI) status was evaluated according to established criteria. The relationship between EBV infection and clinicopathological factors as well as its role on prognosis were investigated.Results420 patients were enrolled in the study and of 53 patients (12.62%) were identified as EBVaGC. EBVaGC was more common in males (p = 0.001) and related to early T stage (p = 0.045), early TNM stage (p = 0.001) and lower level of serum CEA (p = 0.039). No association could be found between EBV infection and HER2 expression, MSI status and other factors (p all > 0.05). Kaplan–Meier analysis revealed that both the overall survival and disease-free survival of EBVaGC patients were similar to that of EBV-negative GC (EBVnGC) patients (p = 0.309 and p = 0.264, respectively).ConclusionEBVaGC was more common in males and in patients with the early T stage and TNM stage as well as patients with lower serum CEA level. Difference in overall survival and disease-free survival between EBVaGC and EBVnGC patients cannot be detected.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients’ cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

S2993 Extensive Hepatic Fibrosis Mimicking Primary Liver Malignancy

Introduction: Liver cirrhosis is a pathophysiological outcome of sustained liver inflammation. Sustained hepatic insults generate a process of fibrogenesis, in which an excessive extracellular matrix deposition replaces normal liver parenchyma. We present a patient with newly diagnosed liver cirrhosis who was found to have a liver mass suggestive of primary liver malignancy on imaging; however, multiple biopsies confirmed the mass to be fibrosis with mild hepatitis. Case Description/Methods: A 40-year-old male presented for the evaluation of new bilateral lower extremity edema. He reported a long history of alcohol use but otherwise denied prior medical history and no medication use. Laboratory work on admission was pertinent for a total bilirubin of 3.5, AST 162, ALT 57, alkaline phosphatase 176, albumin 3.0, and a non-reactive viral hepatitis panel. CT abdomen/pelvis revealed a heterogeneous liver suggestive of cirrhosis along with a 6.8 cm x 8.7 cm mass with irregular margins situated between the right and left lobes of the liver. On 3-phase MR imaging, the lesion demonstrated progressive enhancement in the portal venous phase and hepatic venous phase, with retention of contrast on 5-minute delayed images [Image 1a, b, c]. Overall, these findings suggested infiltrative cholangiocarcinoma. Additional imaging ruled out multifocal disease, and tumor markers CEA and AFP were unremarkable. Subsequently, a diagnostic laparotomy with liver biopsy was performed. The biopsy demonstrated fibrosis with atypical ductular proliferation, but the presence of low-grade infiltrative cholangiocarcinoma could not be ruled out. To rule out biopsy sampling error, two additional biopsies later that month concurred cirrhotic liver segments with areas of mild hepatitis. Tumor markers CK20 and CDX2 were negative, and no atypical cells were present. It was concluded that this liver lesion represented extensive hepatic fibrosis and mild hepatitis due to ongoing alcohol use, but no malignancy. Discussion: Liver cirrhosis is a major risk factor for the development of primary liver cancers such as hepatocellular carcinoma and cholangiocarcinoma. Triple-phase CT or MR imaging plays a key role in diagnosing these cancers; however, as demonstrated in our case, certain benign lesions such as liver fibrosis can mimic primary liver malignancy. Improved recognition of these benign lesions is necessary to avoid unnecessary and potentially harmful interventions.Figure 1.: 1a) Pre-contrast MR T2 weighted image showing a large central hepatic mass and lobular contour of liver consistent with cirrhosis. 1b) Post-gadolinium T1 fat-saturated MR image demonstrating enhancement of the liver lesion in the hepatic venous phase. The lesion showed high retention index of contrast on 5-minute delayed images (not included). 1c) Diffusion-weighted MR image showing the liver lesion with significantly restricted diffusion suggestive of infiltrative type of cholangiocarcinoma.

Testicular tumours from a clinical point of view : What urologists and oncologists need to know from the pathologist about testicular cancer

HintergrundKeimzelltumoren des Hodens sind die häufigste maligne Tumorerkrankung bei Männern im Alter von 15–40 Jahren. Die Unterscheidung von Seminomen und Nichtseminomen hat prognostische Bedeutung und ist für Therapieplanung und Nachsorge essenziell. Durch interdisziplinäre, stadiengerechte Therapie haben Keimzelltumoren generell eine sehr gute Prognose. Eine Übertherapie sollte wegen möglicher Langzeitfolgen vermieden werden. Hierbei hilft die Risikobeurteilung anhand klinischer und pathologischer Faktoren.Ziel der ArbeitDarstellung der (histo-)pathologischen Charakteristika, die die uroonkologische Therapieplanung maßgeblich beeinflussen.Material und MethodenNichtsystematischer Übersichtsartikel über die relevanten (histo-)pathologischen Befunde für die klinische Therapieplanung im interdisziplinären Kontext.ErgebnisseZentrale Pathologiebefunde für Kliniker:Innen sind: (i) Identifikation eines Keimzelltumors, ggf. durch Nachweis eines Chromosom-12p-Zugewinns, (ii) Subtypenspezifizierung und (iii) Angabe von Risikofaktoren (insbesondere Invasion von Lymphgefäßen und/oder Rete testis und Tumorgröße). Molekularpathologische Untersuchungen i. S. von Mutationsanalysen sind angesichts einer sehr geringen Mutationslast und bislang fehlender prädiktiver Marker und zielgerichteter Therapieoptionen nicht Teil der Routinediagnostik.DiskussionEin detaillierter, idealerweise synoptischer histopathologischer Befundbericht ist Grundlage der Planung und Durchführung einer leitlinienkonformen, risikoadaptierten Therapie und neben der bildgebenden Diagnostik und der Bestimmung der Serumtumormarker AFP und β‑HCG (letztere insbesondere bei Nichtseminomen) mitentscheidend, um die guten Heilungsaussichten zu wahren und eine Übertherapie zu vermeiden.Zusatzmaterial onlineZusätzliche Informationen sind in der Online-Version dieses Artikels (10.1007/s00292-022-01113-0) enthalten.

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer.

Objective The aim of this study was to analyze the association between the expression of chromatin assembly factor 1 subunit A (CHAF1A) in gastric cancer (GC) and clinicopathological features, disease prognosis, and expression of programmed cell death-ligand 1 (PD-L1). Material and Methods. A total of 140 GC tissue specimens were collected between January 2013 and December 2017. CHAF1A expression in GC and paracancerous tissues was determined. Then, the associations between CHAF1A expression level in the collected tissues and clinicopathological features as well as PD-L1 expression level were investigated. Cox regression analyses were carried out to determine whether CHAF1A is an independent prognostic factor for GC. Finally, the association between CHAF1A expression levels and survival of the GC patients was investigated. Results A significantly higher level of CHAF1A expression in GC tissues was found compared to that in paracancerous tissues (p=0.042). CHAF1A expression level in GC tissues was found to be strongly associated with family history (p=0.005), smoking history (p=0.016), T stage (p=0.001), tumor marker AFP (p=0.017), tumor marker CEA (p=0.027), and PD-L1 expression (p=0.029). CHAF1A expression was also found to be positively correlated to PD-L1 expression (p=0.012). Moreover, high CHAF1A expression levels were found to lead to poor prognosis (p=0.019). Univariate and multivariate analyses all showed that CHAF1A was an independent poorer prognostic factor for gastric cancer (p=0.021, HR = 1.175, 95% CI: 1.090–2.890 for univariate analyses; p=0.014, HR = 2.191, 95% CI:1.170–4.105 for multivariate analyses). A high level of CHAF1A expression was thus found to be an independent risk factor for GC prognosis. Conclusion High CHAF1A expression is associated with poor GC prognosis and positively correlated to PD-L1 expression. Thus, CHAF1A expression level may be used as a novel biomarker for GC diagnosis.

Surveillance after Complete Response to First-Line Chemotherapy in Patients with Metastatic Nonseminomatous Germ Cell Tumor.

The optimal management of patients with metastatic germ cell tumors who achieve a complete response (CR) after first-line chemotherapy remains unsettled. This study reports long-term outcomes of patients with metastatic germ cell tumor managed with surveillance after achieving a CR to first-line chemotherapy. Patients with metastatic nonseminomatous germ cell tumor treated at Indiana University between 1990 and 2017 who achieved a CR after first-line chemotherapy and were monitored with surveillance were retrospectively analyzed. CR was defined as normalization of tumor markers AFP and hCG, and no residual mass >1 cm in long axis. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Three hundred sixty-seven patients achieved a CR and were managed with surveillance. After a median followup of 4.97 years, 34 patients had disease progression. At most recent followup, 346 (94%) patients were alive with no evidence of disease, 10 patients (2.7%) died of their disease, 5 (1.4%) died of other causes and 6 (1.6%) were lost to followup. The estimated 2-year PFS was 91% (95% CI: 87%-94%) and 2-year OS was 98% (95% CI: 96%-99%). The estimated 2-year PFS by International Germ Cell Cancer Collaborative Group risk category was 92% for good vs 90% for intermediate vs 87% for poor risk (p=0.15), and the estimated 2-year OS was 99% for good vs 96% for intermediate vs 93% for poor risk disease (p=0.001). Patients with metastatic nonseminomatous germ cell tumor who achieve a CR after first-line chemotherapy can be observed. Most patients who relapse can be salvaged with surgery and/or chemotherapy.

The Significance of Serum Tumor Markers CEA, Ca 19-9, Ca 125, Ca 15-3, and AFP in Patients Scheduled for Orthotopic Liver Transplantation: Do Elevated Levels Really Mean Malignancy?

Preparation of the patients for liver transplantation is a meticulous process and includes evaluation of tumor markers to rule out occult malignancy. The present study evaluated the significance of serum tumor markers in patients bound for liver transplantation due to viral and other etiologies of liver failure. Three hundred eighty-one patients who underwent liver transplantation were included in the study. Demographic data, model for end stage liver disease (MELD) scores, and serum tumor marker levels were prospectively collected. AFP levels were significantly higher in viral etiologies when compared to other etiologies (p < 0.05). Ca 19-9 was significantly higher in viral etiologies (p < 0.05). Among the viral etiologies, HCV-related liver failure had higher carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (Ca 19-9) levels (p < 0.05). A correlation was found between increasing MELD scores and serum levels of tumor markers (p < 0.05). Tumor markers such as AFP, CEA, Ca 125, and Ca 19-9 can be elevated in end stage liver disease. Their levels vary according to etiology and severity of disease. The diagnostic capabilities of these markers are reduced in end stage liver disease setting but they contribute to the evaluation of the pathophysiology of chronic liver disease. Transplantation can be performed safely in cases with high tumor marker levels provided that any occult malignancy is ruled out by means of imaging and endoscopic techniques. Tumor markers can guide the physician in determining the severity of liver cirrhosis, and further studies are needed to validate such a relationship.

Efficacy of radioembolization with Yttrium-90 for treatment hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide. Radioembolization with Yttrium-90 is a safe, effective locoregional therapy for unresectable HCC.Purpose: This study aimed to evaluate the safety and efficacy of radioembolization with Yttrium-90 for the treatment of HCC.Materials and methods: A total of 93 patients were diagnosed with HCC and treated by radioembolization with Yttrium-90 from 2013 to 2021 at Bach Mai Hospital. Radiographic findings on computed tomography (CT) or magnetic resonance imaging (MRI) were assessed by using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Patient survival was assessed using the Kaplan-Meier method, and prognostic factors affecting survival were assessed using Cox proportional hazards regression.Results: The mean age of 93 patients was 59.0±9.8 years. Mean tumors diameter was 6.5 ± 2.7 cm, the mean of tumor marker AFP is 1812 ± 6577 ng/ml. Complete response and partial response to treatment were observed in 21 (40.4%) and 15 patients (28.8%) of 52 follow-up patients. The median overall survival (OS) was 12.0 [95% CI: 5.0-25.0] months. Factors associated with longer OS included BCLC stage A-B, ECOG 0 and no portal vein thrombosis.Conclusion: Radioembolization with Y-90 is safe and effective in patients with unresectable HCC. BCLC stage A-B, ECOG 0 and no portal vein thrombosis were positive prognostic factors

A highly sensitive silicon nanowire array sensor for joint detection of tumor markers CEA and AFP.

Liver cancer is one of the malignant tumors with the highest fatality rate and increasing incidence, which has no effective treatment plan. Early diagnosis and early treatment of liver cancer play a vital role in prolonging the survival period of patients and improving the cure rate. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) are two crucial tumor markers for liver cancer diagnosis. In this work, we firstly proposed a wafer-level, highly controlled silicon nanowire (SiNW) field-effect transistor (FET) joint detection sensor for highly sensitive and selective detection of CEA and AFP. The SiNWs-FET joint detection sensor possesses 4 sensing regions. Each sensing region consists of 120 SiNWs arranged in a 15 × 8 array. The SiNW sensor was developed by using a wafer-level and highly controllable top-down manufacturing technology to achieve the repeatability and controllability of device preparation. To identify and detect CEA/AFP, we modified the corresponding CEA antibodies/AFP antibodies to the sensing region surface after a series of surface modification processes, including O2 plasma treatment, soaking in 3-aminopropyltriethoxysilane (APTES) solution, and soaking in glutaraldehyde (GA) solution. The experimental results showed that the SiNW array sensor has superior sensitivity with a real-time ultralow detection limit of 0.1 fg ml-1 (AFP in 0.1× PBS) and 1 fg ml-1 (CEA in 0.1× PBS). Also, the logarithms of the concentration of CEA (from 1 fg ml-1 to 10 pg ml-1) and AFP (from 0.1 fg ml-1 to 100 pg ml-1) achieved conspicuously linear relationships with normalized current changes. The R2 of AFP in 0.1× PBS and R2 of CEA in 0.1× PBS were 0.99885 and 0.99677, respectively. Furthermore, the sensor could distinguish CEA/AFP from interferents at high concentrations. Importantly, even in serum samples, our sensor could successfully detect CEA/AFP. This demonstrates the promising clinical development of our sensor.

A Nonlinear Association between Tongue Fur Thickness and Tumor Marker Abnormality: A Cross-Sectional Study.

Background Many associations between tongue fur and different physiological and biochemical indexes have been revealed. However, the relationship between tongue fur and tumor markers remains unexplored. Methods We collected the medical examination reports of 1625 participants. Participants were residents of Chengdu, China, undergoing routine health checkups at the health management center of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. The participants' tongue fur thickness was measured using the DAOSH four-diagnostic instrument. Tumor marker levels, including t-PSA, AFP, CEA, CA125, and CA199, were measured in the clinical laboratory. Curve-fitting and multivariable logistic regression were used to analyze the association between tongue fur thickness and tumor marker abnormality. Results Curve-fitting showed that the relationship between tongue fur thickness and abnormal tumor marker rate was nonlinear, similar to a U shape. As the tongue fur thickness value increased, the abnormal tumor marker probability initially decreased and then increased. Logistic regression showed that, in the crude model, compared with the thin tongue fur group, the odds ratios (ORs) and 95% confidence intervals (CIs) of the less or peeling tongue fur group and thick tongue fur group for tumor marker abnormality were 1.79 (1.02–3.17) and 1.70 (1.13–2.54), respectively. After adjusting gender, age, body mass index (BMI), smoking history, drinking history, tongue color, the form of the tongue, and fur color, the ORs and 95% CIs of the less or peeling tongue fur group and thick tongue fur group were 1.93 (1.04–3.57) and 1.82 (1.17–2.81), respectively. Conclusions Excessive or very little tongue fur is associated with tumor marker abnormality. Further cross-sectional studies are needed to evaluate the clinical value of tongue fur for cancer diagnosis and screening.

Clinical Effect of Iodine-125 Seed Implantation in Patients with Primary Liver Cancer and Its Effect on Th1/Th2 Cells in Peripheral Blood.

Objective To investigate the clinical effect of iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer and the effect on peripheral blood Th1/Th2 cells. Methods A total of 136 patients with primary liver cancer from April 2017 to June 2018 were selected as subjects and randomly divided into the control group and observation group with 68 cases in each group. The control group was treated with chemotherapy, and the observation group was treated with iodine-125 seed implantation on the basis of the control group. After 3 months of treatment, the curative effect was investigated. Serum tumor markers, peripheral blood Th1/Th2 cells, and side effects and recurrence rate were compared between the two groups. Results The levels of serum tumor markers in both groups at 3 months after treatment were lower than before treatment (P < 0.05). Three months after treatment, the levels of tumor markers AFP, AFP-L3, and GP73 in the observation group were 14.61 ± 3.49 μg/L, 3.29 ± 0.41 ng/mL, and 51.24 ± 4.51 μg/L, respectively, which were lower than those in the control group, 32.53 ± 4.59 μg/L, 5.63 ± 0.63 ng/mL, and 71.52 ± 6.05 μg/L (P < 0.05). At 3 months after treatment, the level of including interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) in Th1 cells of the observation group was higher than that of the control group (P < 0.05), whereas the levels of IL-4, IL-6, and IL-10 in Th2 cells were lower than those in the control group (P < 0.05). There was no statistical significance in the incidence of leukopenia, thrombocytopenia, and gastrointestinal reactions between the two groups (P > 0.05). The recurrence rate of the observation group at 12, 24, and 36 months after treatment was lower than that of the control group (P < 0.05). Conclusion Iodine-125 seed implantation combined with chemotherapy in patients with primary liver cancer can reduce the level of serum tumor markers, improve the level of peripheral blood Th1/Th2 cells, and reduce the recurrence rate of patients without increasing the incidence of side effects, which is worthy of promoting the application of iodine-125 seed implantation.

Generation of Dual functional Nanobody-Nanoluciferase Fusion and its potential in Bioluminescence Enzyme Immunoassay for trace Glypican-3 in Serum.

Glypican-3 (GPC3) is a serological biomarker for the diagnosis of Hepatocellular carcinoma (HCC), but it is a challenging task to develop a bioassay for determination of the trace GPC3 in serum. In this study, Bioluminescense immunoassay based on bifunctional nanobody-nanoluciferase fusion was developed with the ultra-sensitive feature to achieve this goal. First, nanobodies special against GPC-3 binder as biological recognition element were generated by immunization and phage display technology. Second, The best clone GPN2 was fused with nanoluciferase as a dual-functional immunoreagent to establish an ultra-sensitive bioluminescence enzyme immunoassay (BLEIA), which is 30 and 5 times more sensitive than the traditional colorimetric assay and fluorescent assay, respectively. The cross-reactivity analysis of BLEIA showed that there was no cross-reactivity with HCC related tumor markers AFP, CEA, CA19-9 and GPC1/GPC2. The limit of detection (LOD) of developed BLEIA was 1.5 ng/mL, which assured its application in the diagnosis of GPC3 in 94 serum samples. This study indicates that BLEIA based on nanobody-nanoluciferase fusion could be used as a useful tool for the diagnosis of HCC patients.

To explore the curative effect of CT-guided Iodine-125 radioactive seed implantation in the treatment of stage Ⅳprimary hepatocellular carcinoma

ObjectivesTo explore the clinical efficacy and survival of CT-guided Iodine-125 radioactive seed implantation in the treatment of stage Ⅳ primary hepatocellular carcinoma. MethodsA retrospective study of 62 patients with primary hepatocellular carcinoma in our hospital from January 2017 to December 2018 [60 males, 2 females, age (52.76 ​± ​10.82) years old], All patients were implanted with Iodine-125 radioactive seeds under CT guidance, followed up regularly after operation to observe the clinical efficacy, including comparison of changes in cancer size before and after treatment, tumor marker AFP, and improvement in complications such as abdominal pain and ascites. Follow-up 3–36 months to assess patient survival. ResultsAmong the 62 patients, 3 months after Iodine-125 radioactive seed implantation, 5 cases (8.1%) had complete remission of cancer, 33 cases (53.2%) had partial remission, 12 cases (19.4%) had stable lesions, and 12 cases (19.4%) had disease progression. The effective rate was 61.3%. The tumor volume (31.44 ​± ​14.51cm3) was significantly smaller than before (50.96 ​± ​30.13cm3) (t ​= ​5.303, p ​< ​0.05). The tumor marker AFP (69.28 ​± ​50.99) ug/L of 3 months after implantation was significantly lower than that before treatment (90.63 ​± ​68.58) ug/L (t ​= ​3.702, P ​< ​0.05). The average survival time of Iodine-125 seed implantation for stageⅣhepatocellular carcinoma is 11.47 ​± ​0.85 months, and the median survival time is 9 months. The survival time of the group with better pathological differentiation (gradeⅠ+Ⅱ) was significantly better than that of the group with poor differentiation (grade Ⅲ+Ⅳ) (x2 ​= ​6.869 p ​< ​0.05). Among the 38 patients with different degrees of abdominal pain, 22 patients improved better than before; 15 of 28 patients with different degrees of ascites were better than before. All patients had no serious complications related to treatment. ConclusionsIodine-125 radioactive seed implantation therapy can safely and effectively treat hepatocellular carcinoma, and relieve the clinical symptoms of abdominal pain and ascites.