Low false-positive lymph nodes for 18F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer.

OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard. METHODS: Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities. RESULTS: For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9-97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055). CONCLUSION: 18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis.

Assessing osteoporosis and bone mineral density through 18F-NaF uptake at lumbar spine.

OBJECTIVES: The use of 18F-Sodium fluoride (NaF) PET/CT is established in the detection of metastatic bone disease, yet its utility in osteoporosis remains underexplored. This research aims to assess the variations in 18F-NaF uptake among individuals with differing bone mineral density (BMD) and to examine the relationship between 18F-NaF uptake and BMD. METHODS: In this retrospective study, 199 patients (average age 56 ± 6, comprising 52 males and 147 females) with a history of cancer were analyzed. Each participant underwent both 18F-NaF PET/CT and lumbar dual-energy X-ray absorptiometry (DXA) scans within a span of 7 days. Based on DXA outcomes, patients and their lumbar vertebrae were categorized into normal BMD, osteopenia, and osteoporosis groups. The lumbar 18F-NaF uptake across these groups were compared, and to explore the association between lumbar standardized uptake values (SUV) values and BMD. The efficacy of 18F-NaF uptake in diagnosing osteoporosis or osteopenia was also evaluated. Analysis was conducted using Mann-Whitney U tests, Spearman regression, and receiver operating characteristic (ROC) curve analysis through GraphPad Prism 10.0. RESULTS: A total of 796 lumbar vertebrae from 199 patients were measured. It was observed that osteoporotic patients had significantly lower 18F-NaF uptake than those with osteopenia and normal BMD across the L1-L4 lumbar vertebrae (P < 0.0001). In a vertebra-based analysis, normal BMD vertebrae exhibited the highest maximum SUV(SUVmax) compared to osteopenic (8.13 ± 1.28 vs. 6.61 ± 1.01, P < 0.0001) and osteoporotic vertebrae (8.13 ± 1.28 vs. 4.82 ± 1.01, P < 0.0001). There was a positive correlation between lumbar 18F-NaF uptake and BMD across all vertebrae, with correlation coefficients exceeding 0.5 (range: 0.57-0.8). The area under the ROC curve values were notably high, at 0.96 for osteoporosis and 0.83 for osteopenia diagnosis. CONCLUSION: This study demonstrates distinct 18F-NaF uptake patterns among individuals with varying BMD levels, with a positive correlation between 18F-NaF uptake and BMD. These findings highlight the potential of 18F-NaF PET/CT as a supportive diagnostic method in the management of osteoporosis.

Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An Open-Label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Single-cell transcriptome reveals a novel mechanism of C-Kit+-liver sinusoidal endothelial cells in NASH.

AIM: To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH). METHODS: We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+-LSECs were determined using coculture and bone marrow transplantation (BMT) methods. RESULTS: Three special clusters of single-LSEC were differentiated. C-Kit+-LSECs of cluster 0, Msr1+-LSECs of cluster 1 and Bmp4+Selp+-VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit+-primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit+-LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit+-LSECs or the livers of MCD mice receipting of C-Kit+-BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit+-endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH. CONCLUSIONS: Hence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit+-LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression.

Laparoscopic sleeve gastrectomy makes acid reflux symptoms worse or better?: a prospective short-term observational study in patients with morbid obesity.

BACKGROUND: Gastroesophageal reflux symptom (GERS) occur frequently in obese patients. Although some surgeons avoid laparoscopic sleeve gastrectomy (LSG) in these patients for fear of postoperative exacerbation of GERS, this notion is not supported by sufficient medical evidence. OBJECTIVES: This prospective study aimed to evaluate the impact of LSG on GERS. SETTING: Shanghai East Hospital, Shanghai, China. METHODS: Seventy-five LSG candidates were enrolled between April 2020 and October 2021. Only patients with completed preoperative and 6-month postoperative evaluation of GERS with the Reflux Symptom Score (RSS) and the Gastrointestinal Quality of Life index were included. Each patient's characteristics, including sex, age, drinking and smoking history, body mass index (BMI) at the time of surgery, recent BMI, comorbidities, glucose and lipid metabolism-related laboratory results, and uric acid and sex hormone levels were obtained. RESULTS: Sixty-five patients (33.8 ± 9.1 years) were finally included in our study. The mean preoperative BMI was 36.4 ± 6.8 kg/m2. Preoperative GERS were reported in 32 (49.2%) patients (RSS > 13), and 26 of them (81.3%) had dramatic remission at 6 months postoperatively. Four patients (12.1%) developed de novo GERS postoperatively, which were well-controlled with oral proton pump inhibitors. Furthermore, GERS were significantly correlated with preoperative BMI; the risk of developing new or worsening GERS postoperatively was positively associated with preoperative insulin resistance. CONCLUSIONS: A low incidence of de novo GERS and significant alleviation in preoperative GERS occurred in most obese patients after LSG. A patient with preoperative insulin resistance may not be suitable for LSG surgery owing to the increased risk of new or worsening of GERS postoperatively.

Assessment of Autologous Blood marker localIzation and intraoperative coLonoscopy localIzation in laparoscopic colorecTal cancer surgery (ABILITY): a randomized controlled trial.

BACKGROUND: Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy. METHODS: The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18-80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing. DISCUSSION: This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient's quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022.

Atrazine promotes breast cancer development by suppressing immune function and upregulating MMP expression.

There is evidence that the triazine herbicide atrazine, which is used extensively, is present in both surface water and groundwater, and its interfering effect on immune systems, endocrine systems, and tumours has been reported by laboratory and epidemiological studies. This study explored how atrazine affected 4T1 breast cancer cell development in vitro and in vivo. The obtained results showed that after exposure to atrazine, the cell proliferation and tumour volume were significantly increased and the expression of MMP2, MMP7, and MMP9 was upregulated. The thymus and spleen indices, the CD4 + and CD3 + lymphocyte percentages which from the spleen and inguinal lymph nodes, and the CD4 + /CD8 + ratio were noticeably lower than they were in the control group. Importantly, tumour-infiltrating lymphocytes such as CD4 + , CD8 + , and NK cells were decreased while Treg cells were increased. Moreover, IL-4 was increased and IFN-γ and TNF-α were decreased in the serum and tumour microenvironment. These results suggested that atrazine can suppress systemic as well as local tumour immune function and upregulate MMPs to promote breast tumour development.

LncRNA LINC01871 sponging miR-142-3p to modulate ZYG11B promotes the chemoresistance of colorectal cancer cells by inducing autophagy.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor in the digestive tract. Increasing evidence indicated that chemoresistance leads to a poor prognosis of CRC. Herein, we aimed to uncover the potential mechanism by which long intergenic noncoding RNA-1871 (LINC01871) affects the chemoresistance of CRC cells. METHODS: Relative level of LINC01871 in CRC tissues was assessed by reverse transcription quantitative PCR (RT-qPCR). Kaplan-Meier analysis was conducted to determine the relevance of LINC01871 and the prognosis of CRC patients. Cell Counting Kit-8 (CCK-8) and colony formation assay were used to evaluate the proliferation of SW480 cells. Expression levels of proteins and their genes were assessed by western blot, immunofluorescence staining and RT-qPCR. In addition, the interaction of LINC01871, miR-142-3p and protein zyg-11 homolog B (ZYG11B) were analyzed via dual-luciferase reporter assays. RESULTS: LINC01871 was low-expressed in CRC tissues and cell lines. Patients with a low level of LINC01871 showed significantly lower survival rate. pcDNA-LINC01871 significantly reduced the viability of SW480 cells ( P < 0.01), elevated SW480 cells sensitivity to 5-FU ( P < 0.01), reduced LC3 punctate aggregates ( P < 0.01) and downregulated the relative mRNA expression level of autophagy related protein 9A, autophagy related protein 4B and high mobility group box 1 ( P < 0.01) in SW480 cells. Moreover, LINC01871 was found to sponge miR-142-3p, and ZYG11B was the target of miR-142-3p. MiR-142-3p mimic significantly recovered the effect of pcDNA-LINC001871, whereas pcDNA-ZYG11B reversed the recovery effect of the miR-142-3p mimic. CONCLUSION: LINC01871/miR-142-3p/ ZYG11B axis regulates the chemoresistance of CRCs by inducing autophagy.

KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma.

Background: The incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC. Methods: The mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1. Results: KNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes. Conclusion: KNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC.

Cu2+-mediated turn-on fluorescence biosensor based on DNA-templated silver nanoclusters for label-free and sensitive detection of adenosine triphosphate.

A Cu2+-mediated turn-on fluorescence biosensor based on the DNA-templated green-emitting silver nanoclusters (DNA@g-AgNCs) was developed for label-free and sensitive detection of adenosine 5'-triphosphate (ATP). Cu2+ was able to quench the bright green fluorescence of DNA@g-AgNCs because of the coordination and photoinduced electron transfer between DNA@g-AgNCs and Cu2+. Therefore, a unique and effective fluorescence biosensor can be constructed with the formation of DNA@g-AgNCs/Cu2+/ATP ternary-competition system. With the introduction of ATP, the DNA@g-AgNCs/Cu2+ fluorescence sensing system will be disrupted and the fluorescence of DNA@g-AgNCs was recovered due to higher affinity of ATP towards Cu2+. On the basis of this feature, the DNA@g-AgNCs/Cu2+ fluorescence sensing system demonstrated quantitative determination of ATP in the range 0.05 - 3 µM and a detection limit of 16 nM. Moreover, the fluorescence sensing system was successfully applied to the quantitative determination of ATP in human urine and serum samples with recoveries ranging from 98.6 to 106.5%, showing great promise to provide  a label-free, cost-efficient, and rapid platform for ATP-related clinical disease diagnosis.

The Modified Glasgow Prognostic Score Predicts Survival in Gastric Cancer Patients with Normal CEA and CA19-9.

Background: Traditionally, serum CEA and CA19-9 levels are good prognostic factors for gastric cancer. Many gastric cancer patients do not have elevated CEA or CA19-9 levels even at a very advanced stage. This study investigates the significance of the modified Glasgow prognostic score (mGPS) for the survival of gastric cancer patients with normal CEA and CA19-9. Methods: We retrospectively examined 488 curatively resected gastric cancer patients with normal preoperative serum levels of CEA and CA19-9 to evaluate the prognostic ability of mGPS for overall survival. The prognostic significance was analyzed by univariate and multivariate analyses. Results: Age, hemoglobin, white cell count, and neutrophils were each significantly correlated with the mGPS. Multivariate analyses showed that tumor location (HR, 0.803; 95% CI, 0.667-0.966; P=0.020), TNM stage (HR, 2.714; 95% CI, 2.250-3.275; P < 0.001), and mGPS (HR, 1.042; 95% CI, 1.105-1.772; P=0.023) were significantly associated with overall survival. Significant correlations were found between overall survival and mGPS. The Kaplan-Meier analysis demonstrated significant differences among patients with mGPS of 0, 1, and 2 (P < 0.001), with the mortality rate being higher for patients with a higher mGPS. Conclusion: The mGPS can predict survival in gastric cancer patients with normal CEA and CA19-9.

IL36 indicating good prognosis in human Hepatocellular Carcinoma.

Background and Aim: Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men before the age of 60 years in China. Interleukin (IL)36 played important roles in antitumor immune responses, but its role in HCC is still unknown. We aimed to explore the correlation between IL36 and prognosis of HCC patients. Methods: The expression of IL36 was measured by Immunohistochemistry (IHC), serum Enzyme-linked Immunosorbent Assay (ELISA) and flow cytometry (FCM). Chi-square test was performed to analyze the relationship between IL36 expression and clinical parameters of HCC patients. The correlation between IL36 expression and prognosis of HCC patients was evaluated by Kaplan-Meier method and Cox regression analysis. Results: The IL36 expression in HCC tumor samples was lower than that in paired peri-tumor samples; the analyses suggested that there was no correlation between IL36 expression and age, gender, and tumor size, but tight relationship between IL36 expression and liver cirrhosis, metastasis and some other clinical parameters. The results of Kaplan-Meier analysis indicated positive expression of IL36 could induce high survival rate of patients. The detection of IL36 with ELISA suggested that expression of IL36 in serum was the highest in patients of HCC, other than the chronic hepatitis patients and the healthy. The result of FCM suggested the expression of IL36 was higher in CD4+ T cells than other immune cells. Conclusions: There is a close relationship between the expression of IL36 and the prognosis of HCC, higher expression of IL36 suggested better prognosis and longer survival of HCC.

Long non-coding RNA LINC01503 promotes colorectal cancer cell proliferation and invasion by regulating miR-4492/FOXK1 signaling.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) are closely associated with the progression of human cancer, including colorectal cancer (CRC). A previous study suggested that lncRNA LINC01503 promotes squamous cell carcinoma progression. However, the function of LINC01503 in CRC has remained elusive. The present study indicated that LINC01503 was significantly upregulated in CRC tissues compared with that in adjacent normal tissues as detected by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that knockdown of long intergenic non-protein coding RNA (LINC)01503 markedly inhibited the proliferation and invasion of CRC cells, whereas overexpression of LINC01503 had the opposite effects, as indicated by Cell Counting kit-8 and Transwell assays. Mechanistically, it was revealed that LINC01503 serves as a sponge for microRNA (miR)-4492, which targets forkhead box K1 (FOXK1) in CRC cells. In addition, luciferase reporter assays demonstrated the direct binding of miR-4492 mimics to LINC01503 and to a sequence in the 3'-untranslated region of FOXK1. Furthermore, it was demonstrated that overexpression of LINC01503 reduced the availability of miR-4492 in CRC cells. Furthermore, miR-4492 mimics inhibited FOXK1 expression, while simultaneous overexpression of LINC01503 abolished this effect. Finally, it was demonstrated that restoration of FOXK1 abolished the inhibitory effect of LINC01503 knockdown on CRC cell proliferation and invasion. Taken together, the present results suggested that LINC01503 promotes CRC progression via acting as a competing endogenous RNA for miR-4492/FOXK1.

MiR-629-5p promotes colorectal cancer progression through targetting CXXC finger protein 4.

MiR-629-5p has been shown to function as a tumor promoter in some types of cancer. However, the role of miR-629-5p in colorectal cancer remains unclear. Here, the significant up-regulation of miR-629-5p in colorectal cancer tissues and cell lines was observed. Overexpression of miR-629-5p showed a positive effect on cell proliferation and migration. The enhanced miR-629-5p level also suppressed cell apoptosis and resulted in a low Bax level and a high Bcl-2 level. Further down-regulating miR-629-5p demonstrated opposite effects. CXXC finger protein 4 (CXXC4) was predicted as a direct target of miR-629-5p Dual-luciferase reporter and Western blotting assays exhibited miR-629-5p directly bound to the 3'UTR of CXXC4 and then down-regulated its expression at post-transcriptional level. CXXC4 knockdown rescued the decreased cell proliferation and migration and the enhanced cell apoptosis induced by inhibiting miR-629-5p expression. Notably, overexpression of miR-629-5p also conferred 5-fluorouracil sensitivity, which was partly abrogated by coexpression of CXXC4. Overall, the results presented here suggest that miR-629-5p functions as a tumor promoter by improving proliferation and migration and repressing apoptosis and 5-FU sensitivity in colorectal cancer progression by directly down-regulating CXXC4.

Improved electrochemical performance of LiCoO2 electrodes with ZnO coating by radio frequency magnetron sputtering.

Surface modification of LiCoO2 is an effective method to improve its energy density and elongate its cycle life in an extended operation voltage window. In this study, ZnO was directly coated on as-prepared LiCoO2 composite electrodes via radio frequency (RF) magnetron sputtering. ZnO is not only coated on the electrode as thin film but also diffuses through the whole electrode due to the intrinsic porosity of the composite electrode and the high diffusivity of the deposited species. It was found that ZnO coating can significantly improve the cycling performance and the rate capability of the LiCoO2 electrodes in the voltage range of 3.0-4.5 V. The sample with an optimum coating thickness of 17 nm exhibits an initial discharge capacity of 191 mAh g(-1) at 0.2 C, and the capacity retention is 81% after 200 cycles. It also delivers superior rate performance with a reversible capacity of 106 mAh g(-1) at 10 C. The enhanced cycling performance and rate capability are attributed to the stabilized phase structure and improved lithium ion diffusion coefficient induced by ZnO coating as evidenced by X-ray diffraction, cyclic voltammetry, respectively.

Over-expression of human carcinoma-associated antigen in intrahepatic cholangiocellular carcinoma.

OBJECTIVE: To investigate the expression status of human carcinoma antigen (HCA) in human cholangiocellular carcinomas, and to determine the relationship between HCA and clinical features. METHODS: Tissues from 60 intrahepatic cholangiocellular carcinoma (ICC) patients, and normal liver tissues from 20 hepatic hemangioma patients selected randomly were assayed for the expression of HCA by immunohistochemistry, and Western blots. Areas of poorly differentiated (n=20), moderately-well differentiated (n=30), highly differentiated tumors (n=10) from different cases were evaluated. Results were recorded as positive (≥5% of cells staining and staining intensity 2+ or 3+) or negative (<5% of cells staining and staining intensity<2+) and analyzed using the χ2 test. RESULTS: BCE075 and BDD048 antibodies showed similar staining patterns. The positive immunostaining of BCE075 was mainly localized in the cytoplasm and cell secretions. The staining was positive in 15% of poorly differentiated ICC, 72% of moderately-well differentiated, 100% of highly differentiated tumors. But, staining was not detected in adjacent normal tissue. The differences in HCA expression among these tissues were statistically significant. Also, we found expression of HCA to be closely associated with the degree of differentiation of ICC and tumor cell morphology. There was a correlation between expression of HCA and serum CA19-9. CONCLUSION: The data suggest that HCA is a potential marker for the diagnosis of cholangiocellular carcinoma.