Tumor Differentiation Research Articles

Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens

Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.

Clinical and histopathological features of advanced cutaneous squamous cell carcinoma with varying responses to cemiplimab.

Most patients with unresectable locally advanced cutaneous squamous cell carcinoma (cSCC) benefit from cemiplimab, but some do not respond. Our study aims to identify clinical and histopathological features predicting response to cemiplimab. We analyzed 15 patients treated with cemiplimab, assessing clinical, demographic, histopathological, and immunohistochemical characteristics and correlating them with treatment response. Furthermore, effectiveness and safety were evaluated in our cohort. Our cohort included 12 males and 3 females, with a mean age of 78.1years. The majority of tumors, accounting for 66.7%, were located in the head and neck region. Treatment was well-tolerated, with only one grade3 colitis. There was no correlation between immune-related adverse events and treatment response. Non-responders were younger (69.4 vs. 82.5years). A history of hematological malignancy correlated with poorer response. High mitotic rate, poor tumor differentiation, high vimentin and p53, and low E-cadherin expression were associated with worse response. Conversely, higher intratumoral inflammatory infiltrate density, presence of necrotic areas, and lower mismatch repair-protein staining correlated with better response. Cemiplimab is a safe and effective therapy, particularly in elderly patients. Well-differentiated tumors with low proliferative index, intratumoral inflammatory infiltrate, and tumor necrosis may predict better clinical response.

The role of neutrophils-lymphocytes ratio (NLR), lymphocytes-monocytes ratio (LMR), platelets-lymphocytes ratio (PLR) in oral cancer and acute dental infections

Objectives: The present study was a cross-sectional observational study, which was carried out on patients reported to the Department of Oral Medicine and Radiology. This study aims to evaluate the hemogram parameters NLR, LMR, and PLR among 90 Patients. Methods: Patients were divided into 3 groups: Group A consists of 30 patients with histopathological confirmed oral cancer. Group B consists of 30 patients who presenting acute dental infections. Group C consists of 30 patients clinically healthy subjects. The hemogram parameters NLR, LMR and PLR were compared in the 3 groups and we studied their correlation to the clinical prognostic indicators like T stage, to the presence or absence of lymph node metastasis, and to differentiation of cancer. After obtaining personal informed consent, a thorough examination of the oral cavity and the lesion was conducted with an illuminated light and mouth mirror. Blood tests were performed on all the subjects before treatment. Under aseptic conditions, Venous blood (2 ml) was collected by venepuncture of the median cubital vein in the cubital fossa of the forearm using a disposable syringe with a 24-gauge needle. The withdrawn blood was transferred into an EDTA-containing test tube. Haematological parameters were analysed using an automated haematology analyzer. NLR, LMR, and PMR were calculated as the ratio of absolute peripheral neutrophil to lymphocyte, lymphocyte to monocyte, and platelet to lymphocyte count, respectively. Results: The present study revealed that NLR is significantly elevated in oral carcinoma compared to healthy individuals, but is lesser than in patiemts with acute dental infections. LMR is higher in oral carcinoma than in acute dental infections and healthy individuals, but no statisticaly significant difference was detected among the groups. PLR is higher in oral carcinoma than in Acute dental infections and healthy individuals, and it is statistaicaly significant. There are significant correlations in oral carcinoma between NLR, LMR, and PLR. NLR has a positive correlation with PLR and a negative correlation with LMR, which showed clinical significance as determined by the Spearman correlation coefficient. In Acute dental infections and healthy individuals, there is a significant correlation of NLR with LMR and PLR but no significant correlations between LMR and PLR and vice versa. NLR, LMR, and PLR were correlated to clinical prognostic indicators like T stage, presence or absence of lymph node metastasis, and differentiation of cancer. There is no significant difference in NLR, LMR, or PLR ratios concerning Clinical T staging since the p-value is greater than 0.05 for NLR, LMR, and PLR (p= 0.072, 0.446, 0.446, respectively). A statistically significant difference is found in LMR to the clinical presence or absence of Lymph node metastasis since the p-value is less than 0.05 only for LMR (p=0.018). The mean values of LMR in N0, N1, and N2 were 9.49, 5.65, and 4.40, respectively; this implies that the mean value of LMR decreases in advanced oral carcinoma as the nodal stage increases with lymph node metastases. A statically significant difference is found in NLR (p=0.011) and PLR (p =0.013) for differentiation of tumour (p-value is less than 0.05), which implies NLR & PLR values are elevated in moderate differentiated oral carcinomas when compared to well-differentiated oral carcinoma. Conclusions: A significant elevation exists in haematological parameters like NLR, LMR, and PLR in oral carcinoma and acute dental infections.

Clinical Significance of HHLA2 as a Novel Therapeutic Target for Colorectal Cancer.

Colorectal cancer (CRC) is a high-indence malignance of the digestive system with a high mortality rate in the world. The results are desired to provide an important theoretical basis for discovering new therapeutic targets for CRC. The expression of human endogenous retrovirus-H-long terminal repeat association protein 2 (HHLA2) in human CRC was detected to explore its correlationship with clinicopathological features and prognosis of patients and its potential in treating CRC. Western blot was employed to detect HHLA2 expression in fresh tissues obtained from 6 CRC patients' excisions, including cancer, paracancer, and normal issues. Immunohistochemical staining was employed to determine HHLA2 expression in paraffin-embedded specimens of 139 patients with colorectal cancer, and its relationship with the clinicopathological profiles and survival was analyzed. Small interfering RNA (siRNA) targeting HHLA2 was used to transfect CRC cells to silent HHLA2. MTT, plate colony formation, cell scratch, and Transwell assay were conducted to observe the proliferation, migration, and invasion of CRC cells. HHLA2 protein was expressed in human colorectal cancer tissues, paracancer tissues and normal tissues, which was significantly upregulated in cancer tissues (P<0.01). HHLA2 expression level in CRC tissues showed a close correlationship with the invasion depth of the tumor (P=0.000), metastasis of regional lymph nodes (P=0.018), clinical stage (P=0.010), and patient survival (P=0.011). Correlation with gender (P=0.873), age (P=0.864), location of the tumor (P=0.768), degree of tumor differentiation (P=0.569) and distant metastasis (P=0.494) exhibited no significance. The survival time of CRC patients with high and low HHLA2 expression groups was 43.231 months and 55.649 months, respectively, with a statistical difference between the two groups (P=0.001). Silencing HHLA2 inhibited proliferation, migration and invasion of CRC cells significantly. HHLA2 is overexpressed in CRC tissues which is associated with poor prognosis of patients. HHLA2 might be recognized as a new candidate for adjuvant diagnosis and prognosis of CRC, as well as a promised new target for immunotherapy of CRC.

IL-33/ST2 Signaling and its Correlation with Macrophage Heterogeneity and Clinicopathologic Features in Human Intrahepatic Cholangiocarcinoma.

IL-33/ST2 signaling plays crucial roles in the development and progression of various human malignancies. However, its significance in intrahepatic cholangiocarcinoma (ICC) still remains unclear. This study aimed to investigate the expression of IL-33/ST2 signaling and its correlations with macrophage heterogeneity and ICC patients' clinicopathologic features. The expression of different phenotype macrophage markers and IL-33/ST2 signalingrelated markers was detected. The correlation between L-33/ST2 signaling and different phenotype macrophage markers as well as ICC patients' clinicopathologic data was evaluated. Massive heterogeneous cancer cells and PAS-positive cells were observed in tumor tissues. CD68-positive cells accumulated in tumor tissues and expression of both M1 phenotype markers and M2 phenotype macrophage markers was higher in tumor samples than para-carcinoma samples. However, M2 phenotype macrophages represented the dominant macrophage population in ICC tissues. Plasma levels of IL-33, ST2, and MIF were evidently enhanced in ICC patients compared to healthy controls. IL-33/ST2 signaling-related markers exhibited a massive increase in tumor samples than para-carcinoma samples. IL-33 and ST2 expression in ICC tissues was positively associated with M1 and M2 phenotype macrophages. Plasma levels of IL-33, ST2, and MIF were correlated with the diameter of tumor lesions, lymph node metastasis, TNM stage, and tumor differentiation degree. Multivariate analysis demonstrated IL-33 expression to exhibit a correlation with the diameter of tumor lesions, lymph node metastasis, and TNM stage. Additionally, there was a relationship observed between ST2, MIF expression, and diameter of tumor lesions plus TNM stage. IL-33/ST2 signaling exhibited a positive relationship with macrophage heterogeneity in ICC tissues, and upregulated levels of IL-33, ST2, and MIF were associated with aggressive clinicopathologic characteristics. These findings may provide promising diagnostic biomarkers and potential therapeutic strategies for ICC patients targeting IL-33/ST2 signaling.

Targeted Positron Emission Tomography-Tracked Biomimetic Codelivery Synergistically Amplifies Ferroptosis and Pyroptosis for Inducing Lung Cancer Regression and Anti-PD-L1 Immunotherapy Efficacy.

The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed 124I-P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of 124I-P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of 124I-P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. 124I-P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8+ T cells, and CD4+ T cells in tumor tissues (P < 0.05). The combination of 124I-P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, 124I-P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.

Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression: An Updated Meta-analysis.

A systematic review and meta-analysis. To conduct a meta-analysis of studies that compared surgery with or without radiotherapy to radiotherapy alone for patients with malignant spinal cord compression, and a subgroup analysis of patients stratified by hematologic and solid malignancies. Two previous meta-analyses showed that surgery with or without radiotherapy was better than radiotherapy alone in patients with malignant spinal cord compression. Nevertheless, there was no stratification by tumor type, leading to uncertainty regarding best approach for patients with hematologic malignancies. We searched PubMed, Scopus, and Web of Science, for studies comparing surgery with or without radiotherapy to radiotherapy alone in patients with malignant spinal cord compression. The primary outcomes were improvement in ambulatory status and survival at 12 months. For neurological outcomes, we included studies involving both locally advanced primary malignancies of the spine and metastatic tumors. We restricted our analysis to studies on metastases for survival outcomes. We included 2536 patients from 18 studies. Surgery was performed in 890 (35%) patients. The pooled analysis of all studies revealed that improvement in ambulatory status (OR 2.65; 95% CI 1.60-4.39) and survival at 12 months (OR 1.66; 95% CI 1.10-2.52) were significantly higher in patients who underwent surgery with or without radiotherapy. Improvement in ambulatory status (OR 1.92; 95% CI 1.19-3.09) and survival at 12 months (OR 4.24; 95% CI 2.35-7.66) were significantly higher in patients with hematologic malignancies in the surgical arm. The primary outcomes were not significantly different between patients with solid malignancies. Surgical intervention demonstrates superior neurological outcomes and increased survival compared with radiotherapy alone. Subgroup analysis revealed that patients with hematologic malignancies on surgery group experienced superior primary outcomes; however, high risk of bias of the included studies preclude definitive changes in standard care based on this data. These findings underscore the need for further research regarding the efficacy of surgical versus radiotherapeutic approaches for specific tumor types. 2.

BTN2A1: A Novel Target to Boost Tumor Killing Capacity of Human γδ T Cells.

γδ T cells have recently raised great interest as effector cells in cancer immunotherapy because of their HLA-independent mode of action and their broad tumor reactivity. To translate the application of γδ T cells into clinically effective immunotherapies, specific tumor targeting and/or boosting of γδ T-cell activation in vivo seem to be a critical step. In this issue, Le Floch and colleagues report a new strategy for enabling γδ T cells to be specifically activated to kill acute lymphoblastic leukemia cells and solid tumor cells using agonistic BTN2A1 antibodies. See related article by Le Floch et al., p. XX .

High Entropy 2D Layered Double Hydroxide Nanosheet Toward Cascaded Nanozyme-Initiated Chemodynamic and Immune Synergistic Therapy.

High-entropy nanomaterials (HEMs) are a hot topic in the fields of energy and catalysis. However, in terms of promising biomedical applications, potential therapeutic studies involving HEMs are unprecedented. Herein, we demonstrated high entropy two-dimensional layered double hydroxide (HE-LDH) nanoplatforms with versatile physicochemical advantages that reprogram the tumor microenvironment (TME) and provide antitumor treatment via cascaded nanoenzyme-initiated chemodynamic and immune synergistic therapy. In response to the TME, the multifunctional HE-LDHs sequentially release metal ions, such as Co2+, Fe3+, and Cu2+, exhibiting exquisite superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPX) activities. The multiple enzymatic activities convert specific tumor metabolites into a continuous supply of cytotoxic reactive oxygen species (ROS) to relieve hypoxia under a TME. Thus, HE-LDHs facilitate robust nanozyme-initiated chemodynamic therapy (NCDT), achieving high therapeutic efficacy without obvious side effects. In addition, the release of Zn2+ from the HE-LDH matrix triggers the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling pathway, boosting the innate immunotherapeutic efficacy. The intratumoral applications of the nanocomposite in tumor-bearing mice models indicate that HE-LDH-mediated NCDT and immune synergistic therapy effectively upregulated the expression of relevant antitumor cytokines and induced cytotoxic T lymphocyte infiltration, showing superior efficacy in inhibiting tumor growth. Therefore, this work opens a new research direction toward synchronized NCDT and immunotherapy of tumors using HEMs for advanced healthcare.

Ligand-Based targeting in drug delivery system

Targeted drug delivery system has come up as a new approach that increase the effectiveness of the drug while reducing the side effects of cancer therapy. This review focuses on the application of ligand-based drug targeting, especially antibodies-drug conjugates in the case of ovarian cancer and folate-receptor targeting in the case for tumor cells. This review will provide analytical insights about the effectiveness of two approaches on improving bioavailability, targeting specific tumor cells, and enhancing drug carrying capacity. The findings show that folate receptor targeting does has significant potential in enhancing curcumin’s anticancer activity. However, there are still challenges such as rapid decomposition of curcumin. This review also highlights the need for future experiments and research to consolidate the effectiveness of the drug delivery system and explore their potential in broader clinical environment.

Targeting the undruggable in glioblastoma using nano-based intracellular drug delivery.

Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.

Tumor Differentiation is Correlated with Estrogen Receptor Beta (ERβ) Expression but Not with Interleukin-6 (IL-6) Expression in Colorectal Carcinoma

BACKGROUND: Colorectal carcinoma (CRC), the third most common malignant disease worldwide, is associated with estrogen receptor β (ERβ) and interleukin-6 (IL-6). ERβ is known to down-regulate IL-6 in prostate cancer, lung carcinoma, and CRC cell lines; however, its effect on human with CRC remains unclear. Therefore, this study was conducted to investigate the association between ERβ and IL-6 expressions with the clinicopathological features of CRC.METHODS: This was an analytic observational study using 40 paraffin blocks of CRC patients. ERβ and IL-6 expression was measured by immunohistochemistry (IHC) staining. The percentage of immunoreactive tumor cell per 1000 cells was manually recorded and tumor differentiation as well as tumor infiltration were determined. Tumor differentiation was graded according to the World Health Organization (WHO) 2010 criteria, while tumor infiltration was defined based on the American Joint Committee on Cancer (AJCC) 8th edition.RESULTS: Fifty percent of samples were well-differentiated CRC, and 57.5% samples were T3 infiltration tumors. IHC staining showed 35.5% of samples were positive for ERβ expression, while 70.86% were positive for IL-6 expression. There were negative correlation of ERβ expression with tumor differentiation (p=0.018; r=-0.371), but no correlation with tumor infiltration (p=0.836) were found. There was no correlation between ERβ expression with IL-6 expression (p=0.154).CONCLUSION: There is statistically significant correlation between tumor differentiation and ERβ expression, wherein improved tumor differentiation is linked to higher levels of positive ERβ expression. However, there is no discernible relationship between IL-6 and tumor differentiation. These findings suggest that while IL-6 was involved in the growth of the tumor, ERβ expression might have an impact on tumor differentiation.KEYWORDS: colorectal carcinoma, estrogen receptor beta, interleukin-6, cell differentiation

Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus

BackgroundHepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses.MethodsscRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC.ResultsThese analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results.ConclusionThese results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.

A study of the clinical significance of mSEPT9 in monitoring recurrence and prognosis in patients with surgically treated colorectal cancer.

To explore the medical significance of methylated septin9 (mSEPT9) in monitoring recurrence and prognostic assessment in individuals with surgically treated colorectal cancer (CRC). To investigate the role of Septin9 in colorectal cancer, we utilized the TIMER2.0 database to analyze its differential expression between tumor tissues and adjacent normal tissues. Colorectal cancer RNA-seq data from the TCGA database was downloaded and curated. The clinical relevance of mSEPT9 in colorectal cancer was explored by examining the correlation between Septin9 methylation levels and clinical characteristics using UALCAN and MethSurv software. Peripheral blood samples were obtained from 130 CRC subjects who underwent surgery for the detection of mSEPT9 and carcinoembryonic antigen (CEA) expression, along with collection of clinicopathological data such as age, gender, tumor site, TNM stage, and tumor differentiation. Patients were followed up for at least 3 years post-surgery until the death or final follow-up dates (31/12/2022). Additionally, peripheral blood samples were collected from 30 colorectal cancer surgery patients for mSEPT9 detection before and 7 days after surgery. Through bioinformatic database analysis, we identified higher expression levels of SEPT9 mRNA in most tumor tissues compared to normal tissues. Similarly, both paired and unpaired CRC tissues exhibited elevated expression of Septin9 when compared to normal tissues. Following GO and KEGG analysis of Septin9 target genes, we discovered their significant associations with ncRNA metabolic processes, ribonucleoprotein complex biogenesis, spliceosomes, and viral carcinogenesis. Furthermore, the overexpression of mSeptin9 was observed in CRC tissues, and it demonstrated a correlation with colon cancer staging and histologic classification. In our clinical sample study, The positive rate of mSEPT9 in CRC patients 7 days after surgery was 43.44% lower than that of preoperative. The differences in TNM stage, tumor differentiation degree, and preoperative CEA expression level between the preoperative mSEPT9 positive and negative groups of CRC were statistically significant (P < 0.05). Recurrence free survival (RFS) and overall survival (OS) were shorter in the preoperative mSEPT9-positive group, meaning preoperative mSEPT9 status was a risk factor for CRC recurrence and prognosis (P < 0.05). The sensitivity, specificity, and AUC value of preoperative mSEPT9 and CEA levels for predicting postoperative recurrence in CRC patients were 88% vs. 72%, 56.19% vs. 55.24%, and 0.721 vs. 0.636 respectively, well the AUC value of the combined prediction of postoperative recurrence was 0.758. The detection of mSEPT9 combined with CEA in preoperative plasma helps predict recurrence in colorectal cancer patients.

Expression patterns of H3K27me3 for differentiation of breast fibroadenomas and phyllodes tumors.

Phyllodes tumors (PTs) are rare breast tumors showing overlapping features with fibroadenomas (FAs). Diagnosis on small biopsies is challenging. New diagnostic markers are needed. Here we evaluated immunohistochemical staining of histone 3 trimethyl-lysine-27 (H3K27me3) as a diagnostic and prognostic marker in a series of PTs. Surgically removed PTs at our institution (September 1990 and July 2022) and control FAs. Tissue micro-arrays (4 cores, 2 mm Ø) stained with H3K27me3, and scored with QuPath-derived H-score. Fisher exact test, Mann-Whitney U-test and chi-squared test used for group comparison. ROC analysis applied to define cutoffs. Cox proportional hazards models were used for assessing disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) in PTs. We included 81 patients with PTs and 44 patients with FAs. QuPath-derived H-scores of stromal H3K27me3 were statically significantly lower in PTs than in FAs (p < 0.001). We identified exploratory cutoffs to discriminate FAs from benign and malignant PTs (AUC = 0.78 and 0.73, respectively). No associations between DFS, OS, or DSS and H3K27me3 expression were found. H3K27me3 expression differs between FAs and PTs, indicating potential as diagnostic marker, but it is not predictive for DFS, OS or DSS in PTs. Further validation is needed.

Epidemiological profile and clinical characteristics of ocular and periocular tumors in North and Central India.

To describe the epidemiological profile and clinical characteristics of ocular and periocular tumors in patients presenting to three tertiary care referral centers in North and Central India. Hospital-based consortium study. Retrospective, descriptive, observational study. A total of 3184 patients were diagnosed with 3557 ocular and periocular tumors over 11 years from 2010 to 2021. Of these, 2395 (67.33%) were benign, 84 (2.36%) were premalignant, and 1078 (30.30%) were malignant. The most common location was the ocular surface (n = 1294, 37.09%), followed by the eyelid (n = 1185, 33.97%), intraocular (n = 624, 17.88%), and orbit (n = 454, 13.01%). The most common tumors were retinoblastoma (n = 483, 13.57%), ocular surface squamous neoplasia (OSSN) (n = 301, 8.46%), and dermoid cyst (n = 167, 4.69%). In the pediatric age group, retinoblastoma was the most common tumor (n = 483, 13.57%), while in adults, it was OSSN (n = 301, 8.46%). The stage at presentation for malignant tumors was divided into in-situ (57.14%), local spread (8.16%), and metastasis (32.83%). For specific tumor locations, the stages were 78.83%, 17.51%, and 2.18%, respectively, for eyelid tumors; 51.76%, 27.05%, and 17.64%, respectively, for orbital tumors; 88.37%, 5.81%, and 5.19%, respectively for ocular surface tumors; and 35.71%, 14.15%, and 50.28%, respectively, for intraocular tumors. Identifying the epidemiological characteristics of ocular and periocular tumors will aid in early diagnosis and timely intervention. Intraocular tumors showed delayed diagnosis, advanced stages at presentation, and required patients to travel longer distances for treatment, indicating the need for strengthened diagnostic and treatment facilities to improve access to care.

A retrospective study on the prognosis of endoscopic surgery for 385 early glottic cancer patients

Objective: To investigate the prognosis and influencing factors of endoscopic surgery for early glottic carcinoma. Methods: In this retrospective study, we applied the Cox proportional hazards regression model and the random survival forest model to analyze the clinical characteristics of 385 patients [362 males, 23 females, age ranging from 33 to 91 years (62.0±9.6)] who visited the Sixth Medical Center of the General Hospital of the People's Liberation Army from January 2009, to December 2022 and diagnosed with early glottic carcinoma, encompassing variables such as age, gender, T stage, surgical approach, pathological typing, etc. The primary evaluation indicators were overall survival(OS) and disease-free survival rates (DFS). The follow-up duration ranged from 30 to 5,557 days (with a median follow-up time of 1,596 days). Results: After a three-year follow-up, the OS rate for the 385 patients was 95.83%, while the DSF rate was 82.98%. The Cox proportional hazards regression analysis revealed age (HR=2.35, 95%CI: 1.75 to 3.15, P<0.001) and T staging (HR=1.59, 95%CI: 1.13 to 2.23, P=0.019) as predominant factors affecting the OS and DFS. The random survival forest model identified poor tumor differentiation, and high expression of P53 and Ki-67 as predictors of inferior prognosis. Conclusion: Endoscopic surgery for early glottic carcinoma yields favorable short-term OS and reduces short-term recurrence rates, with T-stage emerging as a pivotal factor influencing recurrence. Tumors with poor differentiation and elevated expression of P53 may be indicative of an increased risk of recurrence.

Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p &lt; 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p &lt; 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

A potential target of GXYLT2 affecting the prognosis of gastric cancer by enhancing the EMT process: A clinical retrospective study.

The present study aimed to investigate glucoside xylosyltransferase 2 (GXYLT2) as a potential prognostic marker for gastric cancer (GC). The expression levels of GXYLT2, Notch1, E-cadherin and vimentin in GC and adjacent tissues were detected by Elivision™️ Plus immunohistochemistry. The relationship between GXYLT2, Notch1, E-cadherin and vimentin, and clinicopathological parameters was also analyzed. Univariate and multivariate Cox regression analyses were conducted to evaluate the effect of GXYLT2 on survival. The results revealed that GC tissues exhibited a marked increase in GXYLT2, Notch1 and vimentin, and a marked reduction in E-cadherin. The expression of GXYLT2 was related to the differentiation degree of GC and the pathological tumor-node-metastasis (pTNM) stage; the expression of Notch1 was related to the vascular and nerve infiltration of GC; and E-cadherin and vimentin expression were related to patient age, tumor size, tumor differentiation degree, depth of infiltration, lymph node metastasis and pTNM stage. Positive associations existed between GXYLT2 and Notch1 expression, GXYLT2 and vimentin expression, and Notch1 and vimentin expression. Furthermore, the Kaplan-Meier analysis showed that survival and prognosis were associated with factors such as GXYLT2 protein levels, pTNM stage, tumor dimensions, depth of infiltration and lymph node metastasis. Through Cox regression analysis, GXYLT2 was identified as an independent predictor for GC. In conclusion, GXYLT2 may be related to the pathogenesis of GC, and its abnormal expression could be associated with epithelial-mesenchymal transition. Consequently, GXYLT2 may be considered a promising prognostic marker in the context of GC.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.