Poor Differentiation Research Articles

Lymph node metastasis-related lncRNA GAS6-AS1 facilitates the progression of esophageal squamous cell carcinoma.

Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the adventitia layer (T3 stage), the incidence of lymph node metastasis increases sharply. Abnormal expression of long non-coding RNAs (lncRNAs) has been confirmed in ESCC, but there are still many unknown connections between lncRNAs and lymph node metastasis. We used transcriptome sequencing (RNA-seq) to analyze 10 pairs of ESCC tissues with primary tumor stage T3 and their paired normal epithelium. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to further verify the sequencing results, and survival curve analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate its clinical application value. We investigated the growth and metastasis effects of lncRNA GAS6-AS1 on ESCC cell lines TE-1 and KYSE410 in vitro and in vivo. Other functional experiments included cell apoptosis and cell cycle experiments. Based on our RNA-seq data, lncRNA GAS6-AS1 is highly expressed in ESCC tissues, especially in cancer tissues with lymph node metastasis. The qRT-PCR experiment analysis showed that high expression of GAS6-AS1 was related to poor tumor differentiation and tumor stage. Logistic regression analysis showed that it was an independent risk factor for lymph node metastasis, and ROC analysis validated that it could predict lymph node metastasis. Further survival analysis suggested that high expression of GAS6-AS1 was associated with patients' poor prognosis. In vitro experiments, knocking down GAS6-AS1 inhibited the growth and metastasis of ESCC cells and inhibited tumor growth in vivo. In addition, knocking down GAS6-AS1 can inhibit cell cycle and promote cell apoptosis. Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.

Diagnostic plasma small extracellular vesicles miRNA signatures for pancreatic cancer using machine learning methods

BackgroundIdentifying biomarkers may lead to easier detection and a better understanding of pathogenesis of pancreatic ductal adenocarcinoma (PDAC). MethodsPlasma small extracellular vesicles (sEV) from 106 participants, including 20 healthy controls (HC), 12 chronic pancreatitis (CP) patients, 12 benign pancreatic tumour (BPT) patients, and 58 PDAC patients, were profiled for microRNA (miRNA) sequencing. Three machine learning methods were applied to establish and evaluate the diagnostic model. ResultsThe plasma sEV miRNA diagnostic signature (d-signature) selected using the three machine learning methods could distinguish PDAC patients from non-PDAC individuals, HC, and benign pancreatic disease (BPD, CP plus BPT) both in training and validation cohort. Combining the d-signature with carbohydrate antigen 19-9 (CA19-9) performed better than with each model alone. Plasma sEV miR-664a-3p was selected by all methods and used to predict PDAC diagnosis with high accuracy combined with CA19-9. Plasma sEV miR-664a-3p was significantly positively associated with the presence of vascular invasion, lower surgery ratio, and poor differentiation. MiR-664a-3p was mainly distributed in the PDAC cancer stroma, including fibers and vessels, and was accompanied by VEGFA expression. Overexpression of miR-664a-3p could promote the epithelial-mesenchymal transition (EMT) and angiogenesis. ConclusionIn conclusion, our study demonstrated the potential utility of the sEV-miRNA d-signature in the diagnosis of PDAC via machine learning methods. A novel sEV biomarker, miR-664a-3p, was identified for the diagnosis of PDAC. It can also potentially promote angiogenesis and metastasis, provide insight into PDAC pathogenesis, and reveal novel regulators of this disease.

Revealing the role of necroptosis microenvironment: FCGBP + tumor-associated macrophages drive primary liver cancer differentiation towards cHCC-CCA or iCCA.

Previous research has demonstrated that the conversion of hepatocellular carcinoma (HCC) to intrahepatic cholangiocarcinoma (iCCA) can be stimulated by manipulating the tumor microenvironment linked with necroptosis. However, the specific cells regulating the necroptosis microenvironment have not yet been identified. Additionally, further inquiry into the mechanism of how the tumor microenvironment regulates necroptosis and its impact on primary liver cancer(PLC) progression may be beneficial for precision therapy. We recruited a single-cell RNA sequencing dataset (scRNA-seq) with 34 samples from 4 HCC patients and 3 iCCA patients, and a Spatial Transcriptomic (ST) dataset including one each of HCC, iCCA, and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Quality control, dimensionality reduction and clustering were based on Seurat software (v4.2.2) process and batch effects were removed by harmony (v0.1.1) software. The pseudotime analysis (also known as cell trajectory) in the single cell dataset was performed by monocle2 software (v2.24.0). Calculation of necroptosis fraction was performed by AUCell (v1.16.0) software. Switch gene analysis was performed by geneSwitches(v0.1.0) software. Dimensionality reduction, clustering, and spatial image in ST dataset were performed by Seurat (v4.0.2). Tumor cell identification, tumor subtype characterization, and cell type deconvolution in spot were performed by SpaCET (v1.0.0) software. Immunofluorescence and immunohistochemistry experiments were used to prove our conclusions. Analysis of intercellular communication was performed using CellChat software (v1.4.0). ScRNA-seq analysis of HCC and iCCA revealed that necroptosis predominantly occurred in the myeloid cell subset, particularly in FCGBP + SPP1 + tumor-associated macrophages (TAMs), which had the highest likelihood of undergoing necroptosis. The existence of macrophages undergoing necroptosis cell death was further confirmed by immunofluorescence.Regions of HCC with poor differentiation, cHCC-CCA with more cholangiocarcinoma features, and the tumor region of iCCA shared spatial colocalization with FCGBP + macrophages, as confirmed by spatial transcriptomics, immunohistochemistry and immunofluorescence. Pseudotime analysis showed that premalignant cells could progress into two directions, one towards HCC and the other towards iCCA and cHCC-CCA. Immunofluorescence and immunohistochemistry experiments demonstrated that the number of macrophages undergoing necroptosis in cHCC-CCA was higher than in iCCA and HCC, the number of macrophages undergoing necroptosis in cHCC-CCA with cholangiocarcinoma features was more than in cHCC-CCA with hepatocellular carcinoma features. Further investigation showed that myeloid cells with the highest necroptosis score were derived from the HCC_4 case, which had a severe inflammatory background on pathological histology and was likely to progress towards iCCA and cHCC-CCA. Switchgene analysis indicated that S100A6 may play a significant role in the progression of premalignant cells towards iCCA and cHCC-CCA. Immunohistochemistry confirmed the expression of S100A6 in PLC, the more severe inflammatory background of the tumor area, the more cholangiocellular carcinoma features of the tumor area, S100A6 expression was higher. The emergence of necroptosis microenvironment was found to be significantly associated with FCGBP + SPP1 + TAMs in PLC. In the presence of necroptosis microenvironment, premalignant cells appeared to transform into iCCA or cHCC-CCA. In contrast, without a necroptosis microenvironment, premalignant cells tended to develop into HCC, exhibiting amplified stemness-related genes (SRGs) and heightened malignancy.

TSPO is a novel biomarker for prognosis that regulates cell proliferation through influencing mitochondrial functions in HCC

The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.

Postoperative CT surveillance in the evaluation of local recurrence after sub-lobar resection of neoplastic lesions of the lung

ObjectiveAs indications for sub-lobar resections increase, it will become more important to identify risk factors for postsurgical recurrence. We investigated retrospectively the association between local recurrence after sub-lobar resection of neoplastic lung lesions and pre- and post-operative CT imaging and pathologic features. Materials and methodsWe reviewed retrospectively neoplastic lung lesions with postoperative chest CT surveillance of sub-lobar resections in 2006–2016. We defined “suspicious” findings as nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line and/or progression and explored their association with local recurrence. Primary lung cancer stage, tumoral invasion of lymphatics, visceral pleura or large vessels, bronchial and vascular margin distance were also assessed. ResultsOur study group included 45 cases of sub-lobar resection took for either primary (n = 37) or metastatic (n = 8) lung tumors. Local recurrence was observed in 16 of those patients. New nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line on surveillance CT was significantly associated with local recurrence (p = 0.037). Additionally, solid nodule (p = 0.005), age at surgery ≤60 years (p = 0.006), two or more sites of invasion (p < 0.0001) and poor histologic differentiation (p = 0.0001) were also significantly associated with local tumor recurrence. Of 16 patients with surveillance post-surgical PET-CT, 15 had elevated FDG uptake. ConclusionThe postoperative changes along the suture line should follow a predictable time course demonstrating a pattern of stability, thinning or resolution on CT surveillance. New or increasing postoperative nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line requires close diagnostic work-up. Surgical pathology characteristics added prognostic value on postoperative recurrence surveillance.

Transferrin receptor 1 promotes hepatocellular carcinoma progression and metastasis by activating the mTOR signaling pathway.

Aberrant iron metabolism is commonly observed in multiple tumor types, including hepatocellular carcinoma (HCC). However, as the key regulator of iron metabolism involved in iron absorption, the role of transferrin receptor (TFRC) in HCC remains elusive. The mRNA and protein expression of TFRC were evaluated in paired HCC and adjacent non-tumor specimens. The correlation between TFRC level and clinicopathological features or prognostic significance was also analyzed. The role of TFRC on biological functions was finally studied in vitro and in vivo. The TFRC level was remarkably upregulated in HCC tissues compared to paired peritumor tissues. Overexpressed TFRC positively correlated with serum alpha-fetoprotein, carcinoembryonic antigen, and poor tumor differentiation. Multivariate analysis demonstrated that upregulated TFRC was an independent predictive marker for poorer overall survival and disease-free survival in HCC patients. Loss of TFRC markedly impaired cell proliferation and migration in vitro and notably suppressed HCC growth and metastasis in vivo, while overexpression of TFRC performed an opposite effect. Mechanistically, the mTOR signaling pathway was downregulated with TFRC knockdown, and the mTOR agonist MHY1485 completely reversed the biological inhibition in HCC cells caused by TFRC knockdown. Furthermore, exogenous ferric citrate (FAC) or iron chelator reversed the changed biological functions and signaling pathway expression of HCC cells caused by TFRC knockdown or overexpression, respectively. Our study indicates that TFRC exerts an oncogenic role in HCC and may become a promising therapeutic target to restrain HCC progression.

OGC P47 Yield of staging laparoscopy in upper GI cancer; post COVID

Abstract Background Staging laparoscopy is a useful adjunct in preoperative staging process of oesophago-gastric cancer. NICE recommends use of staging laparoscopy in oesophageal cancer cases where it is likely to guide further management. In cases of gastric cancer there is strong evidence to suggest a high specificity of staging laparoscopy in detection of peritoneal metastasis. During COVID very selective use of staging laparoscopy was adopted by our unit. In this study we aimed to evaluate yield of staging laparoscopy in context of gastric and selective oesophageal cancers in our unit during post-COVID period Methods Retrospective analysis of our prospectively kept database in patients undergoing staging laparoscopy between January 2022 to May 2023 in upper GI tertiary cancer centre was performed. Age, sex, tumour grade, nodal status on radiology, histologic type, differentiation, and site of tumour was assessed against positive cytology and presence of peritoneal or occult visceral metastasis. Multivariate logistic regression was applied to identify independent factors associated with findings. Statistical analysis was carried out using EXCEL® and MedCalc® software. Results Among 104 patients, 69 had oesophageal cancer (OC) and 35 had gastric cancer (GC). In OC group cytology was positive in 4 (5.8%), peritoneal metastasis was present in 7 (10.1%) patients. In GC group positive cytology in 8 (22.8%), peritoneal metastasis was found in 8 (22.8%) patients. On multivariate analysis differentiation, T3+ tumour, lower third cancer, male sex was linked with positive findings in OC group. In GC group poor differentiation, T4 disease, mid body tumour, nodal status of N3 were associated positive findings. Yield of laparoscopy was found to be 17.6% and 34.6% in OC and GC groups respectively. Conclusions Despite of recent advances in radiological modalities, staging laparoscopy remains a useful adjunct in diagnosing peritoneal disease. With negligible complication rates and its relatively high yield in lower third and junctional oesophageal cancer it can be utilised to guide further management and reduce unnecessary laparotomies. Mid gastric body site and T4 cancers in our cohort were strong predictors of peritoneal disease further multi centre research on site of tumour is needed to affirm any such association.

Upregulated TC1 and downregulated Chibby were correlated with the aberrant β-catenin expression in laryngeal squamous cell carcinoma.

As an important member of Wnt/β-catenin signaling pathway, the aberrant expression of β-catenin has been implicated in many cancers. Chibby, a β-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the β-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and β-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, β-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of β-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of β-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of β-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of β-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and β-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of β-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.

Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer.

The programmed death receptor 1/programmed death receptor ligand 1 axis (PD-1/PD-L1) is involved in tumor immune escape and is a potential prognostic biomarker and anti-tumor immunotherapy target in patients with gastric cancer (GC). However, the results of studies obtained in recent years have been inconsistent. The present study aimed to determine the possible predictive significance of PD-L1 in conjunction with three proteins linked with PD-L1 regulation in patients with primary GC. In the present study, the PD-L1, human epidermal growth factor receptor 2 (HER2), cluster of differentiation (CD)133 and microphage-associated CD68 expression levels were identified by multiplexed immunohistochemistry and assessed by automated pathological analysis system in 93 GC tumors and neighboring normal tissues arrayed on the same tissue microarray. All four proteins were statistically analyzed in relation to the clinicopathological characteristics. The expression levels of HER2, CD133 and CD68 were considerably higher in cancer tissues compared with neighboring normal tissues (P<0.05), however, the reverse trend was detected for PD-L1 expression (P=0.0577), particularly in tumor nest (TN; P<0.05). There was no significant correlation between the HER2 and CD133 expression levels and clinicopathological factors. However, significant relationships were found between PD-L1 expression and the TNM stage, pathological differentiation and survival status of patients (P<0.05). Moreover, survival time was prolonged in individuals with elevated PD-L1 expression in TN and GC tissues, but no significant correlation was identified (P=0.0881). The CD68 expression level in tumor stroma, but not in TN, was significantly correlated with poor pathological differentiation in patients with GC (P<0.05). However, PD-L1+CD68+ macrophages were strongly related to lower tumor size (diameter <5 cm), early TNM stage (stage I+II), good pathological differentiation and overall survival in TN (P<0.05). In conclusion, PD-L1+CD68+ macrophage infiltration in TN might be a potential indicator of prognosis in patients with primary GC and merits further investigation.

CD4+CCR8+ Tregs in ovarian cancer: a potential effector Tregs for immune regulation

BackgroundTregs are key drivers of immunosuppression in solid tumors. As an important chemokine receptor on Tregs, the regulatory effect of CCR8 on tumor immunity has received more and more attention. However, the current research on CCR8 in the immune microenvironment of ovarian cancer has not been clear.MethodsBioinformatics analysis was used to compare the transcriptome differences between CD4+ T cells in the peripheral circulation and infiltrated in ovarian tumor tissues. RT-PCR was used to detect the expression levels of chemokine receptor-related differential genes on CD4+ T cells in peripheral blood and ovarian tumor tissues. Multiparameter flow cytometry was used to detect the proportion and phenotypic characteristics of CD4+CCR8+ Tregs and CD4+CCR8− Tregs in different sample types. The expression level of CCR8 ligands was detected at multiple levels. To explore the important role of CCR8-CCL1 and CCR8-CCL18 axis in the migration and invasion of CD4+CCR8+ Tregs into ovarian tumor tissues by establishing a chemotaxis system in vitro.ResultsIn this study, significantly different gene expression profiles were found between peripheral circulating CD4+ T cells and infiltrating CD4+ T cells in ovarian tumor tissues, in which chemokine-chemokine receptor signaling pathway was significantly enriched in all three groups of differential genes. The expression level of CCR8 in infiltrating CD4+ T cells of ovarian cancer tissue was significantly higher than that in peripheral blood of healthy controls and ovarian cancer patients, and high expression of CCR8 was significantly correlated with advanced tumor stage and poor differentiation. CD4+CCR8+ Tregs are the main type of infiltrating CD4+ Tregs in ovarian tumor tissues, which have stronger immunosuppressive phenotypes, secrete more inhibitory cytokines and have stronger proliferation ability. The ligands CCL1 and CCL18 corresponding to CCR8 were significantly overexpressed in ovarian tumor tissues, and the CCR8-CCL1 and CCR8-CCL18 axis played a key role in the migration and infiltration of CD4+CCR8+ Tregs into ovarian tumor tissues.ConclusionsThe results of this study may help to understand the phenotypic characteristics and recruitment process of Tregs in the tumor, and provide new ideas for improving the immunosuppressive status of the ovarian cancer microenvironment.

Dental-derived stem cells in tissue engineering: the role of biomaterials and host response.

Dental-derived stem cells (DSCs) are attractive cell sources due to their easy access, superior growth capacity and low immunogenicity. They can respond to multiple extracellular matrix signals, which provide biophysical and biochemical cues to regulate the fate of residing cells. However, the direct transplantation of DSCs suffers from poor proliferation and differentiation toward functional cells and low survival rates due to local inflammation. Recently, elegant advances in the design of novel biomaterials have been made to give promise to the use of biomimetic biomaterials to regulate various cell behaviors, including proliferation, differentiation and migration. Biomaterials could be tailored with multiple functionalities, e.g., stimuli-responsiveness. There is an emerging need to summarize recent advances in engineered biomaterials-mediated delivery and therapy of DSCs and their potential applications. Herein, we outlined the design of biomaterials for supporting DSCs and the host response to the transplantation.

Analysis on the Development Strategy of Starbucks' Layout in Third and Fourth Tier Cities in China

Recent surveys found that the stores of Starbucks are mostly located in first and second tier cities in China and its objective customers are high income earners. However, in its 2025 expansion plan, the main objective of Starbucks is to enter low tier cities in China due to the high consumption potential in those cities. In order to help Starbucks achieve its plan, this paper will use the SWOT model to analysis internal strength and weakness, external opportunities and threats of Starbucks. The paper found that Starbucks has high user viscosity, strong monopoly power and financial capacity. Besides, the economic conditions in low tier cities are also beneficial to Starbucks such as low cost on daily life bringing out higher level of disposable income and increasing demand for coffee. In the contrast, we found that Starbucks has several problems such as inefficient chain of command, cost pressure due to large investment on digital technology and poor product differentiation. Whats worse, there is fierce battle among other brands and undeveloped consumption concept in the low tier cities. According to the analysis above, we suggest that Starbucks should adopt some strategies such as price discrimination strategy, making product differentiation, increasing investment in digitization and new retail, enhancing the brand influence, seeking for new suppliers with lower prices, shutting down underperforming stores and making improvement on quality of product, service and environment.

The impact of indirect notification of a cancer diagnosis and a risk model based on it to predict the prognosis of postoperative stage T3 esophageal cancer patients.

Chinese doctors are required to inform patients' direct relatives of a cancer diagnosis rather than the patients themselves. The disease may be hidden from patients by their family members, which could result in severe outcomes. We selected postoperative T3 esophageal cancer (EsC) patients hospitalized from June 2015 to December 2019 as research subjects. The patients were divided into a direct-notification group and an indirect-notification group. Several variables were used to evaluate both groups' 36-month progress-free survival (PFS). A risk prediction model of prognosis based on the risk score was established, which was assessed using the area under the curve (AUC) of the receiver operating characteristic curve. One hundred and thirteen patients were enrolled in the training group and forty-eight in the validation group. Cox multivariate regression analysis revealed that males, late stage, poor pathological differentiation, and indirect notification were independent worse risk factors for postoperative T3 stage EsC patients at 36-month PFS (hazard ratio (HR) = 0.454, 95% confidence interval (CI): 0.254-0.812, P = .008; HR = 1.560, 95% CI: 1.006-2.420, P = .047; HR = 0.595, 95% CI: 0.378-0.936, P = .025; HR = 2.686, 95% CI: 1.679-4.297, P < 0.001, respectively). The type of notification was the best correlation factor. The risk score was calculated as follows: risk score = 0.988 × cancer notification (indirect = 1, direct = 0)-0.790 × sex (female = 1, Male = 0) + 0.445 × stage (IIIB = 1, IIA + IIB = 0)-0.519 × pathological differentiation (moderately + well = 1, poorly = 0). The model had a sensitivity of 64.8% and specificity of 81.8%, with the AUC at 0.717 (95% CI: 0.614-0.810) in internal verification, and a sensitivity of 56.8% and specificity of 100%, with the AUC at 0.705 (95% CI: 0.651-0.849) in external validation. The model had good internal and external stability. The model showed a Brier score of 0.18. Indirect notification of a cancer diagnosis was an important negative predictor of postoperative EsC patients' PFS. The model displayed good accuracy and stability in the prediction of risk for cancer progression.

Lymphoepithelial carcinoma of nasal cavity and sinuses: An analysis of survival stratified by demographic features.

169 Background: Lymphoepithelial carcinoma is a rare type of cancer that can often impact the nasal cavity and sinuses. It is characterized by poor differentiation of epithelial cells and an abundance of lymphocytes. Clinically, it is hard to distinguish from other cancers, and surgical management is considered the standard of care. Using patient information found in the Surveillance, Epidemiology, and End Results (SEER), this study identifies associations between survival rates and demographic factors. Previous research has not examined these relationships, so this study seeks to fill this gap in knowledge and better understand survival outcomes. Methods: We identified 4,114 patients with lymphoepithelial carcinoma in the nasal cavity and maxillary sinus. 3,234 patients were later used in the survival analysis, which excludes patients who are alive with no survival time and cases labeled as “All Death Certificate Only and Autopsy Only”. Demographic factors examined include: age, race, gender, median income, and treatment. We then used survival, frequency, and rate tables to measure survival outcomes. Survival tables determined 1, 2, 3, 4, and 5-year survival rates. The nasal cavity and maxillary sinus were selected as sites to focus on since they were consistent with the ICD 8082 classification. The SeerStat software was used in the analysis. Results: The study had more male (60.7%) than female (39.3%) patients, and patients were mainly White (76%), compared to Black (12.6%), Asian (10.3%), American Indian (.632%), and Unknown (.486%). Most individuals (73.6%) were over the age of 55 when the diagnosis was made. For surgical treatment, no discrepancies were identified among racial groups. However, differences were noted in other areas. Survival tables still revealed differences in 5-year survival rate by race (Table 1). The Unknown group had the highest survival rate (67.3%, z= 1.898), followed by Asian (48.8%, z= 1.854), White (42.5%, z= -0.165), Black (38.9%, z= -1.303), and American Indian (28.7%, z= -2.087). Meanwhile, 5-year survival for males and females were 41.1% and 44.1% respectively. Conclusions: This is the first SEER study focusing on correlations between demographic characteristics and survival outcomes for patients with this type of cancer. Given the variance in 5-year survival rates, future research should investigate for differences in the long-term management of lymphoepithelial carcinoma of the nasal cavity and maxillary sinus.[Table: see text]

Hepatocellular carcinoma: tumor heterogeneity and recurrence after preoperative locoregional therapy.

How locoregional therapy (LRT) may change tumor compositional and functional heterogeneity, consequently contributing to treatment resistance and tumor recurrence remains largely unknown. A series of hepatocellular carcinomas (HCCs) treated with preoperative locoregional therapy (LRT) that relapsed after surgery was studied. Thirty HCCs comprising 15 patients treated with LRT prior to liver transplantation (n = 14)/surgical resection (n = 1) were studied. Five patients undergoing pre-transplant LRT, comprising 11 HCCs, presented tumor recurrence (median recurrence time = 10months). Clinicopathological data and immunoexpression of proliferation markers (Ki67, p53), cholangiocytic/hepatic progenitor cell (HPC) markers (EpCAM)/BerEp4, CK19, CK7) and mesenchymal markers (ASMA, vimentin) were evaluated in tumoral epithelial/stromal cells and in peritumoral parenchyma. Higher grading of tumor differentiation, microvascular invasion and tumoral cell p53 expression significantly associated with recurrence (p < 0.05). Piecemeal necrosis features were more frequent in tumors that recurred (p < 0,05). Tumoral and peritumoral Ki67 expression and EpCAM, CK19 and CK7 expression in tumoral cells tended to be higher in treated tumors that recurred. Peritumoral expression of cholangiocytic/HPC markers and tumoral epithelial and stromal cellular expression of mesenchymal markers tended to be higher for tumors without recurrence. Recurrence after transplant with preoperative LRT might be associated with poor HCC differentiation, higher cellular proliferation rate, peritumoral piecemeal necrosis features and cholangiocytic/HPC phenotypes. Understanding HCC progression factors after LRT might be important for optimizing patient selection for treatment, improving surveillance after LRT and to explore synergies between LRT and systemic targeted therapies to prevent recurrence.

Additional staining for lymphovascular invasion is associated with increased estimation of lymph node metastasis in patients with T1 colorectal cancer: Systematic review and meta-analysis.

Lymphovascular invasion (LVI) is a critical risk factor for lymph node metastasis (LNM), which requires additional surgery after endoscopic resection of T1 colorectal cancer (CRC). However, the impact of additional staining on estimating LNM is unclear. This systematic review aimed to evaluate the impact of additional staining on determining LNM in T1 CRC. We searched five electronic databases. Outcomes were diagnostic odds ratio (DOR), assessed using hierarchical summary receiver operating characteristic curves, and interobserver agreement among pathologists for positive LVI, assessed using Kappa coefficients (κ). We performed a subgroup analysis of studies that simultaneously included a multivariable analysis for other risk factors (deep submucosal invasion, poor differentiation, and tumor budding). Among the 64 studies (18,097 patients) identified, hematoxylin-eosin (HE) and additional staining for LVI had pooled sensitivities of 0.45 (95% confidence interval [CI] 0.32-0.58) and 0.68 (95% CI 0.44-0.86), specificities of 0.88 (95% CI 0.78-0.94) and 0.76 (95% CI 0.62-0.86), and DORs of 6.26 (95% CI 3.73-10.53) and 6.47 (95% CI 3.40-12.32) for determining LNM, respectively. In multivariable analysis, the DOR of additional staining for LNM (DOR 5.95; 95% CI 2.87-12.33) was higher than that of HE staining (DOR 1.89; 95% CI 1.13-3.16) (P = 0.01). Pooled κ values were 0.37 (95% CI 0.22-0.52) and 0.62 (95% CI 0.04-0.99) for HE and additional staining for LVI, respectively. Additional staining for LVI may increase the DOR for LNM and interobserver agreement for positive LVI among pathologists.

Effect of ABO blood group on postoperative overall survival and recurrence-free survival rate in patients with hepatocellular carcinoma after hepatectomy: a multi-center retrospective cohort study

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The survival rate after hepatectomy as the first line of treatment for HCC depends on various factors. This study evaluated the association of the ABO blood group and Rh with overall survival (OS) and Recurrence-free survival (RFS) rate after hepatectomy.MethodsThis multicenter retrospective cohort study reviewed the medical files of 639 HCC patients who underwent hepatectomy from 2010 to 2022 in three medical centers affiliated with the Iran University of Medical Sciences. Patient data, including demographic, clinical, tumor characteristics, and post-surgery outcomes, were collected by referring to the patient’s medical profiles. The Cox proportional hazard investigated the relationship between ABO blood group type and OS and RFS rate after hepatectomy.ResultsThe five-year OS and RFS rates were 25.4% and 18.7%, respectively. The five-year OS (Lok rank:40.89, P:0.001) and RFS rate in patients with blood type A were significantly lower than in non-A patients. (Lok rank:10.8, P:0.001) The multivariate Cox analysis showed that blood type A, age < 45 years, tumor size > 5 cm, Poor tumor differentiation, presence of metastasis, The number of involved lymph nodes ≤ 2, and serum Alpha-Fetoprotein)AFP( level ≥ 400 were significantly related to the decreased survival rate of HCC patients after hepatectomy (P < 0.05) There was no significant association between Rh with OS and RFS (P > 0.05).ConclusionBlood group type A, compared to non-A, can be associated with decreased OS and RFS rates in patients with HCC after hepatectomy.

Endoscopic‐pathological characteristics of early‐onset gastric carcinoma in Vietnamese in the period 2014–2019: A single‐center experience

AbstractTo investigate the time‐trend and endoscopic‐pathological characteristics of early‐onset gastric carcinoma (EOGC) in Vietnamese patients. All patients who underwent upper gastrointestinal endoscopy at a tertiary hospital during the 2014–2019 period and had pathologically confirmed gastric carcinoma were retrospectively recruited. The demographic data and endoscopic and pathological findings from all patients were recorded and analyzed to compare the EOGC group (i.e., ≤40 years of age) with the older group (&gt;40 years of age). Out of 1668 patients with gastric carcinoma, 151 (9.1%) patients were with EOGC. The time‐trend change in the EOGC rate was insignificant during the investigated period (p = .972). The median age of patients with EOGC was 35 (IQR, 32–38). Compared with the older group, EOGC was more likely to present with a female predominance (52.3% vs. 30.7%, p &lt; .001), endoscopically located at the gastric body (34.4% vs. 19.2%, p &lt; .001), presented with a diffuse infiltrative appearance (18.9% vs. 11.7%, p = .011) but were less likely to have superficial gastric cancer morphology (0.0% vs. 4.5%, p = .009). Pathologically, it was more likely to have diffuse type (36.4% vs. 23.9%, p = .001) and poor differentiation (90.6% vs. 62.7%, p &lt; .001). EOGC in Vietnamese individuals is not rare, and its incidence has not significantly changed during the studying period. The majority of EOGC was poorly differentiated carcinoma. This study reported the different endoscopic distribution and appearance of EOGC from gastric carcinoma in older patients requiring attention during endoscopic examination.

Cytoplasmic CCR7 (CCR7c) Immunoexpression Is Associated with Tumor Invasion in Gastric Cancer

Background: This study investigates the CCR7 chemokine receptor’s prognostic value in gastric cancer and its relationship to metastasis.&#x0D; Materials and Methods: Normal and adjacent tumor cells in 70 patients with gastric cancer were evaluated for CCR7 expression using immunohistochemical staining. The prognostic values of high and low levels of expression of CCR7 were also evaluated by multivariate and univariate analyses.&#x0D; Results: Analysis indicated high expression of CCR7 in 52.9% of tumor tissue. Moreover, high expression of CCR7 was significantly related to metastasis of lymph nodes (p = 0.00). In addition, high expression of CCR7 had a positive correlation to the disease stage (p = 0.00), age of ≥50 years (p = 0.019), male gender (p = 0.024), vascular involvement (p = 0.009), histology of tumor adenocarcinoma (p = 0.00), and poor tumor differentiation (p = 0.00). However, the high expression of the CCR7 marker was not related to the tumor size.&#x0D; Conclusion: Based on our results, CCR7 expression in gastric cancer can be considered a clinical prognostic indicator in patients with gastric cancer.

Tripartite motif containing 33 demonstrated anticancer effect by degrading c‑Myc: Limitation of glutamine metabolism and proliferation in endometrial carcinoma cells.

Tripartite motif containing 33 (TRIM33) has been reported to be involved in various tumor progression. However, its role in endometrial carcinoma (EC) remains to be elucidated. By mining the publicly available databases UALCAN and TIMER, low expression of TRIM33 was found in tumor tissues of EC patients. Clinically, downregulation of TRIM33 in EC tissues was positively correlated with the extensive muscle invasion and poor differentiation grade. Invitro, experiments performed on human HEC‑1‑A and AN3CA cells showed that overexpression of TRIM33 inhibited the proliferation, migration and invasion of EC cells, whereas TRIM33 knockdown resulted in the opposite results. Furthermore, upregulation of TRIM33 significantly inhibited the glutamine uptake and decreased the intracellular glutamate in EC cells, which is evidenced by the reduction of solute carrier family 1 member 5 and glutaminase. Invivo, TRIM33 also dramatically inhibited tumor growth and glutamine metabolism. Additionally, co‑immunoprecipitation assay confirmed the interaction between TRIM33 and c‑Myc. Overexpression of TRIM33 could reduce the protein stability of c‑Myc by promoting its degradation. In addition, upregulation of c‑Myc could reverse the effects of TRIM33 on EC cells. Together, the present study demonstrated that TRIM33 acted as a tumor suppressor in EC, which is manifested in its inhibition of glutamine metabolism and cell growth via promoting c‑Myc protein degradation.