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Introduction: Serum carcinoembryonic antigen (CEA) is prognostic for recurrence and survival in treated NSCLC. This prospective observational study evaluated CEA as a prognostic or surveillance biomarker in resectable early NSCLC., Materials and Methods: 18 patients with histologically confirmed early NSCLC (stage I-IIIA) were recruited from October 2019 to January 2021. The serum CEA was measured pre-operatively, and then at 6, 12, 18 and 24 months post-operatively, in conjunction with routine CT and/or CT-PET surveillance scans., Results: All patients had a curative R0 anatomical resection (lobectomy) with concurrent systematic mediastinal nodal dissection via a uniportal minimally invasive approach under single lung ventilation general anaesthesia. There was no operative, in-hospital or 30-day mortality. 7 patients (39%) had an elevated pre-operative baseline CEA level > 5.0ng/ml. The mean number of nodes sampled intraoperatively was 15. At median follow-up of 42 months, 11/18 (61.1%) patients were recurrence-free. There were no deaths and two recurrences (18.2%) amongst patients with a CEA < 5 (n=11). In the CEA > 5 subgroup (n=7), there were two deaths (28.5%) and 5/7 (71.4%) patients had a radiological recurrence. There was no difference in overall survival however disease-free survival (DFS) was significantly inferior in patients with a baseline CEA > 5. Median DFS was not reached in patients with CEA < 5 and 18 months in those with an elevated CEA > 5 (p<0.001) Conclusion: Almost 40% of local NSCLC patients had an elevated baseline CEA suggesting this is a useful prognostic and surveillance biomarker to incorporate in the routine work-up for any newly diagnosed NSCLC. Despite curative R0 resection and extensive intra-operative mediastinal lymph node sampling, an elevated pre-operative CEA was associated with a significantly reduced DFS and may be a surrogate for more aggressive tumour biology. Such patients will benefit from meticulous post resection surveillance and adjuvant therapy beyond conventional TNM criteria.

Objective: Lung cancer is a common malignant tumor, characterized by being difficult to detect and lacking specific clinical manifestations. This study aimed to find out the risk factors of mediastinal lymph node metastasis and explore the correlation between serum tumor markers and mediastinal lymph node metastasis and lung cancer prognosis.Methods: A retrospective study of 3,042 lung cancer patients (330 patients with mediastinal lymph node metastasis and 2,712 patients without mediastinal lymph node metastasis) collected from the First Affiliated Hospital of Nanchang University from April 1999 to July 2020. The patients were divided into two groups, namely, mediastinal lymph node metastasis group and non-mediastinal lymph node metastasis group. Student’s t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including exploring serum alkaline phosphatase (ALP), calcium hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA-199, CA -153, cytokeratin fragment 19 (CYFRA 21-1), total prostate specific antigen (TPSA), neuron-specific enolase (NSE) levels and the incidence and prognosis of lung cancer mediastinal lymph node metastasis. Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for mediastinal lymph node metastasis.Results: Binary logistic regression analysis showed that carcinoembryonic antigen and CYFRA 21-1 were independent risk factors for mediastinal lymph node metastasis in patients with lung cancer (p < 0.001 and p = 0.002, respectively). The sensitivity and specificity of CEA for the diagnosis of mediastinal lymph node metastasis were 90.2 and 7.6%, respectively; CYFRA 21-1 were 0.6 and 99.0%, respectively.Conclusion: Serum CEA and CYFRA 21-1 have predictive value in the diagnosis of mediastinal lymph node metastasis in patients with lung cancer.

Abstract Background Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4+ cells. Methods Human adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4+ and CA19-9+ cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4+ and CA19-9+ cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis. Results SSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4+ cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4+ cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9+ cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4+ or CA19-9+ cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9+ cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4+ cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4+ cells. Conclusions SSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.

The multi-markers combined detection can make up for the deficiency of single marker detection and significantly increase the positive detection rates of tumors. This study aimed to assess the performance of serum HER-2 extracellular domain (HER-2/neu ECD), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA15-3) in early screening and auxiliary diagnosis of breast cancer. The HER-2, CEA, and CA15-3 serum levels were measured in 164 healthy volunteers, 111 patients with benign nodules (BN), 123 with early breast cancer (EBC), and 25 with advanced breast cancer. In distinguishing health and EBC, the sensitivity and specificity of joint detection of HER-2, CEA, and CA15-3 were 96.75% and 96.95%, respectively; the accuracy was up to 96.19%, and the AUC was 0.994. In the cohort for distinguishing BN from EBC, serum HER-2, CEA, and CA15-3 sensitivities were 77.03%, 75.27%, and 48.65%, respectively. Combined with three markers, the sensitivity was increased to 84.46%, the AUC was 0.834. All in all, through the combined detection of serum HER-2, CEA and CA15-3 levels in healthy volunteers, BN and EBC, our study found that this method can significantly improve the diagnosis level of breast cancer, suggesting that the three markers panel can be used as an effective tool to improve the early screening level, early diagnosis, and clinical intervention of breast cancer.

Despite significant advancements in therapeutic approaches, oral neoplasms remain formidable and life‑threatening conditions that affect a substantial number of individuals worldwide. Within oral malignancies, a subset of cancer stem cells (CSCs) represent a crucial population responsible for tumor initiation and progression. The identification of reliable markers for the detection and characterization of CSCs in solid tumors, particularly in the context of oral cancers, remains an ongoing challenge. Stage‑specific embryonic antigen 3 (SSEA3), previously associated with mesenchymal stem cells and linked to the progression of breast neoplasms and poor prognosis, has yet to be comprehensively elucidated in the context of oral malignancies. The present study aimed to investigate the expression and properties of SSEA3 in 16 distinct subsets of human oral neoplastic cell lines, classified as either CD44 positive (+) or CD44 negative (‑). For the first time, SSEA3 was examined as an indicator of tumorigenicity and resistance to taxane‑derived chemotherapeutic agents. In the majority of oral neoplastic cell lines analyzed, SSEA3 was expressed in a small population of CD44(+) cells. Significantly, SSEA3(+) cells exhibited heightened proliferative activity and upregulated expression of genes associated with stem cells compared with SSEA3(‑) cells. The aforementioned findings suggested that SSEA3 may contribute to the evolution and progression of oral malignancies by fostering tumor growth. Furthermore, SSEA3(+) cells displayed increased sensitivity to taxane‑based pharmaceuticals, indicating the potential for SSEA3 to be a viable target in the treatment schema for oral cavity neoplasms. In conclusion, the present study provides novel insight into the role of SSEA3 in the progression and management of oral neoplasms, potentially paving the way for more effective therapeutic approaches.

Objective: The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. Summary of background data: Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. Materials and Method: From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. Results: In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. Conclusions: CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable. [ABSTRACT FROM AUTHOR]

Objective: Bone marrow has recently been recognized as a novel source of stem cells for the treatment of wide range of diseases. A number of studies on murine bone marrow have shown a homogenous population of rare stage-specific embryonic antigen 1 (SSEA-1) positive cells that express markers of pluripotent stem cells. This study focuses on SSEA-1 positive cells isolated from murine bone marrow in an attempt to differentiate them into insulin-secreting cells (ISCs) in order to investigate their differentiation potential for future use in cell therapy. Materials and Methods: This study is an experimental research. Mouse SSEA-1 positive cells were isolated by Magnetic-activated cell sorting (MACS) followed by characterization with flow cytometry. Induced SSEA-1 positive cells were differentiated into ISCs with specific differentiation media. In order to evaluate differentiation quality and analysis, dithizone (DTZ) staining was use, followed by reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry and insulin secretion assay. Statistical results were analyzed by one-way ANOVA. Results: The results achieved in this study reveal that mouse bone marrow contains a population of SSEA-1 positive cells that expresses pluripotent stem cells markers such as SSEA-1, octamer-binding transcription factor 4 (OCT-4) detected by immunocytochemistry and C-X-C chemokine receptor type 4 (CXCR4) and stem cell antigen-1 (SCA-1) detected by flow cytometric analysis. SSEA-1 positive cells can differentiate into ISCs cell clusters as evidenced by their DTZ positive staining and expression of genes such as Pdx1 (pancreatic transcription factors), Ngn3 (endocrine progenitor marker), Insulin1 and Insulin2 (pancreaticβ-cell markers). Additionally, our results demonstrate expression of PDX1 and GLUT2 protein and insulin secretion in response to a glucose challenge in the differentiated cells. Conclusion: Our study clearly demonstrates the potential of SSEA-1 positive cells to differentiate into insulin secreting cells in defined culture conditions for clinical applications.

Due to the paucity of targetable antigens, triple-negative breast cancer (TNBC) remains a challenging subtype of breast cancer to treat. In this study, we developed and evaluated a chimeric antigen receptor (CAR) T cell-based treatment modality for TNBC by targeting stage-specific embryonic antigen 4 (SSEA-4), a glycolipid whose overexpression in TNBC has been correlated with metastasis and chemoresistance. To delineate the optimal CAR configuration, a panel of SSEA-4-specific CARs containing alternative extracellular spacer domains was constructed. The different CAR constructs mediated antigen-specific T cell activation characterized by degranulation of T cells, secretion of inflammatory cytokines, and killing of SSEA-4-expressing target cells, but the extent of this activation differed depending on the length of the spacer region. Adoptive transfer of the CAR-engineered T cells into mice with subcutaneous TNBC xenografts mediated a limited antitumor effect but induced severe toxicity symptoms in the cohort receiving the most bioactive CAR variant. We found that progenitor cells in the lung and bone marrow express SSEA-4 and are likely co-targeted by the CAR T cells. Thus, this study has revealed serious adverse effects that raise safety concerns for SSEA-4-directed CAR therapies because of the risk of eliminating vital cells with stem cell properties. [ABSTRACT FROM AUTHOR]

Background and Objectives: Serum tumor markers are widely used for diagnosis, prognosis, treatment response, and surveillance. Our study evaluated cancer embryonic antigen (CEA) in patients with appendiceal adenocarcinoma., Methods: The National Cancer Database was reviewed (2004-2011) for patients with surgical treatment for appendiceal adenocarcinoma. Patients were stratified into two groups: normal and elevated CEA. Multivariable adjusted Cox proportional hazards regression analyses were used to determine the independent effect of CEA on survival., Results: Our study consisted of 2867 patients, 54.0% having elevated CEA. Patients with elevated CEA were more likely to have Stage IV disease, be female, and African American; all p < 0.001. Three-year overall survival (OS) was significantly higher with normal CEA (75.5% vs. 62.8%, p < 0.001). On multivariable analysis, elevated CEA was associated with worse survival (hazard ratio 1.49, 95% confidence interval 1.23-1.80). Patients with elevated CEA had improved 3-year OS with neo-adjuvant compared to adjuvant chemotherapy (p = 0.004), while those with normal CEA showed no difference., Conclusions: In patients with surgically treated appendiceal adenocarcinoma, preoperative elevation in CEA independently predicts decreased 3-year survival and correlates with improved OS with neo-adjuvant therapy. CEA levels should be considered in clinical decision-making regarding neo-adjuvant therapy in patients with appendiceal adenocarcinoma., (© 2022 Wiley Periodicals LLC.)

The purpose of the study was to evaluate the prognostic significance of carcinoerembryonic antigen in patients with rectal cancer and correlate its baseline with the degree of therapeutic pathomorphosis after neoadjuvant chemoradiotherapy.Materials and methods. An estimate of the informative value of carcinoerembryonic antigen (CEA) indices in 179 patients with colorectal cancer determined before and after preoperative chemoradiotherapy (CRT) in SOD 50 Gy.Results. Analysis of the results presented in the study showed that in all patients, CRT caused a significant decrease in the level of CEA (–71%) 10 weeks after its end (p < 0.001). In the course of the pathomorphological study, after the neoadjuvant treatment, the first degree of tumor pathomorphism was recorded in 4.5% of patients, II – 38.5%, III – 45%, IV – 12% (the degree of pathomorphosis is not related to the clinical stage and the degree of differentiation of colorectal cancer). It was revealed that patients with III and IV degrees of therapeutic pathomorphosis initially had a CEA level lower, in comparison with patients with grade I-II. Clinical progression of the disease is diagnosed in 24% of cases (43/179). It was noted that in patients with the IV degree of therapeutic pathomorphism of the tumor, no recurrence of the rectal cancer was detected in either case.Conclusion. The results of the study showed that the problem of individual prediction of the effectiveness of combined treatment of the rectal cancer remains very relevant, rather complicated and yet not completely solved. However, it can be assumed that the use of such an indicator as CEA in monitoring patients after the treatment, can serve as a criterion for the sensitivity of colorectal cancer to CRT. Initially low antigen level can be considered as a positive factor of tumor response to ongoing treatment and disease-free survival of patients with locally advanced rectal cancer.

Recognition of abnormal glycosylation in virtually any cancer type has raised a great interest in the glycan-based tumor biomarkers. Our team explored carbohydrate microarrays as a broad-spectrum immunoassay to probe the immunologically potent tumor glycan targets. This effort has led to the identification of a blood group precursor antigen SSEA-0 as a conserved breast cancer (BCA) marker. Since this immunogenic O-core glycan is normally hidden as a cryptic antigen but becomes overexpressed and surface-exposed by metastatic breast cancer cells (MBCA), its potential as a novel immunological target for precision immunotherapy against tumor metastasis warrants a focused investigation., Competing Interests: CONFLICT OF INTEREST STATEMENT There are no conflicts of interest to declare for any of the authors involved in this work.

There has been a lack of research regarding endometrial stem cells in farm animals, and particularly, regarding epithelial stem/progenitor cells. We aimed to identify potential stem cell subpopulations in porcine and bovine endometrium by measuring the expression of selected stem cell markers (OCT3/4, CD44, SSEA-1, SOX10, CD73, and CD117) during the follicular and luteal phases of the oestrous cycle. We studied 28 endometrial tissue samples collected from 14 healthy, cycling pigs and cows. The endometrial mucosa of each sample was divided into basal, middle, and luminal portions, and the immunohistochemical staining intensity and percentages of cells that were marker-positive were recorded for each portion of the endometrium. Expression of OCT-3/4 was identified in the glands and stroma, and that of SOX10 and CD117 was identified in stroma of both porcine and bovine endometrium. In porcine endometrium, CD44 was only expressed in the glands, whereas SSEA-1 was expressed in the glands and stroma. In bovine endometrium, CD73 was only expressed in the glands. Differences in the expression of most of these markers were found between phases of the oestrous cycle and/or portions of the endometrial mucosa. Our data indicate the existence of both epithelial and mesenchymal stem cell subpopulations in the endometrium of pigs and cows during their oestrous cycles. The expression pattern of the stem cell marker SSEA-1 in porcine endometrium suggests a possible alternative location of the epithelial stem/progenitor cell population in the middle portion of the endometrial glands. [ABSTRACT FROM AUTHOR]

We, herein, present a case of a micropapillary variant of bladder cancer metastasizing to lymph nodes in an 87-year male with elevated serum carcinoembryonic antigen (CEA) levels (2637.8 ng/mL). The patient was evaluated for dyspeptic symptoms and elevated CEA levels. Colonoscopy and upper gastrointestinal endoscopy were normal. Contrast-enhanced computed tomography revealed a bladder tumour. Transurethral resection of bladder tumour (TUR-BT) was performed, and histologically, the tumour was reported as urothelial carcinoma (UC), high grade, and pT1. Intravesical Bacillus Calmette-Guérin (BCG) was started three weeks after TUR-BT and continued for two years. F-18 FDG PET/CT scans were performed every six months during the follow-up due to persistently elevated CEA levels. During follow-up, there was no recurrence of UC in the bladder. Two years later, he was admitted again with lymph node swelling in the left inguinal area. A tru-cut biopsy was performed, which showed UC with a micropapillary component. Gemcitabine monotherapy was given, which resulted in partial response, and a significant decline in serum CEA levels (490.17 ng/mL). Key Words: Carcinoembryonic antigen, Urothelial carcinoma, Bladder cancer, Micropapillary variant, Gemcitabine monotherapy.