Patient Tumor Grade Research Articles

Predictive Value of T2*-Weighted Perfusion and T1-Weighted Permeability MRI Parameters in Determining IDH Mutation Status and Grade of Gliomas.

In glioma classification, the isocitrate dehydrogenase (IDH) mutation status is crucial, as it significantly influences treatment approaches and prognosis. This study assessed the performance metrics of perfusion and permeability magnetic resonance imaging (MRI) parameters with optimal cut-offs in differentiating IDH genotype and tumor grade in patients with grade 2-4 gliomas. This retrospective study included 36 patients surgically diagnosed with grade 2-4 glioma (six grade 2, seven grade 3, and 23 grade 4) with known IDH genotypes (23 IDH wild-type, 13 IDH mutant) between November 2021 and August 2023. All patients underwent preoperative perfusion and permeability MRI examinations with a 3.0 Tesla scanner. Parameters were calculated on colored map images. Using the intraclass correlation coefficient, intra- and inter-observer agreement was assessed. Following multiple testing correction, the perfusion parameters with statistically significant differences were subjected to receiver operating characteristic (ROC) analysis. Five MRI parameters (rCBV and rCBF from perfusion; Ktrans, Ve, and Vp from permeability) showed a significant difference between groups in terms of IDH genotype (p 0.001). In ROC analysis, the best parameters in differentiating IDH genotype included rCBV and Ktrans; rCBV with a cut-off of 5.58 achieved an area under the ROC curve (AUC), sensitivity, specificity, and accuracy of 0.883, 95.7%, 76.9%, and 88.8%, respectively. For Ktrans, with a cut-off of 0.0727 min-1, these values were 0.893, 100%, 69.2%, and 88.8%, respectively. In ROC analysis, these two parameters with rCBF and Ve also showed good performance in differentiating low- and high-grade gliomas with an AUC, sensitivity, and accuracy exceeding 0.940, 86%, and 88%, respectively. Perfusion and permeability MRI may provide useful parameters in differentiating the IDH genotype and grade of gliomas.

IMG-34. THE UTILITY OF [18F]FET PET IMAGING IN PAEDIATRIC CNS TUMOURS: A SINGLE INSTITUTION EXPERIENCE IN SYDNEY, AUSTRALIA

Abstract BACKGROUND MRI remains the standard imaging modality in paediatric CNS tumours. Whilst Positron emission tomography (PET) with O-(2-[18F]fluoroethyl)-L-tyrosine ([18F-FET) is a well-established tool in adult central nervous system (CNS) tumours, established data on its diagnostic utility and impact on clinical management in children and adolescents remain limited. METHODS Single centre retrospective review of database of all paediatric and adolescent patients (age 0-19years) who underwent 18F]FET-PET imaging with cross referencing of patient electronic medical records. Conducted at the Children’s Hospital at Westmead in Sydney, Australia. RESULTS 116 patients underwent 18F-FET PET imaging between October 2012 and January 2024. 28 patients had additional comparative fluorodeoxyglucose (FDG) CNS dedicated PET imaging. Primary indications for FET PET imaging included differentiating between a neoplastic versus non-neoplastic process (23.3%), identifying active residual tumour (14.7%), characterising tumour grade in patients including in those with the known tumour predisposition syndromes (6%), distinguishing between progression pseudo-progression (2.5%) and providing additional localisation or biopsy guidance (8.6%). Malignant transformation, gliomatosis and extent of disease was also noted as indications. 15 patients were able to avoid a biopsy or invasive surgery. Nearly 60% of FET PET imaging was considered clinically useful with the management of 52/112 (46%) patients being supported or changed. Management changes included change second look surgery, change of radiation field, change of treatment and access to a clinical trial. Only 3 scans were reported to have technical challenges in resolution or poor spatial correlation with MRI. Further analysis is currently being conducted, reviewing standard uptake values (SUV’s) of histologically proven low/high grade tumours and T2 enhancing/non-enhancing lesions. CONCLUSIONS This small study demonstrated the clinical benefit and utility of 18F-FET PET imaging in paediatric CNS tumours. Our experience has demonstrated significant surgical and diagnostic advantage in tumour localisation as well as avoiding surgery where able.

Pre-operative Plateletcrit vs. Neutrophil to Lymphocyte Ratio in Predicting Biological Tumor Behavior in Patients with T1-4, N0, M0 Renal Cell Carcinoma: A Retrospective Analysis

Background: Renal cell carcinoma (RCC) is an aggressive cancer prevalent worldwide. Objectives: We investigated whether preoperative serum levels of plateletcrit (PCT) can predict tumor stages and pathological grades in patients, who were operated on for T1-4, N0, and M0 RCC. Additionally, we compared it with neutrophil to lymphocyte ratio (NLR). Methods: We conducted a retrospective evaluation of 196 patients, who had undergone nephrectomy (radical or partial) for T1-4, N0, and M0 RCC at our hospital from January 2016 to December 2022. Based on their histopathology results, tumor stages (T) and WHO-ISUP grades (G) were identified. The patients were separated into two categories depending on their T-stage (T1 - T2 and T3 - T4) and pathological grade (G1 - 2 and G3 - 4). The study compared the NLR, PCT, and their combined values to determine their role in predicting aggressiveness based on pathological stage and grade of tumors. Results: The mean cut-off values for NLR and PCT were found to be 2.108 and 0.273, for the high tumor stage and 2.237 and 0.252 for high-grade tumors, respectively. The statistical analysis showed that NLR (P = 0.031) and PCT (P = 0.006) were significant predictors of high tumor stage, while only PCT (P = 0.022) was a significant predictor of high WHO-ISUP grade. The combination of both NLR and PCT helps improve the sensitivity for detecting high-grade tumors. Conclusions: NLR and PCT can be predictive markers of the tumor stage. However, only PCT can predict the tumor grade in patients with RCC. In addition, combining the PCT and NLR scores improved the predictive ability of each parameter, especially for identifying high-grade tumors.

ASO Visual Abstract: Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

ASO Visual Abstract: Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

Correlation between 18-FDG standardized uptake value and tumor grade in patients with resectable non-small cell lung cancer.

Positron-emission tomography (PET) is widely used for staging lung cancer. Although a correlation between the fluorodeoxyglucose standardized uptake value (SUV) and the histologic grade of the tumor has been shown in several studies, little is known about the impact of different clinical variables on this correlation. This study aimed to evaluate the correlation between tumor SUV and tumor grade in a large cohort of patients and to analyse the impact of clinical factors on this correlation. This retrospective cohort study including patients with non-small cell lung cancer age 18-90 years, with clinical stage I-IVA, who underwent curative-intent lung resection. Data from 726 patients was included in this study. There was a strong correlation between SUV and primary tumor grade in the whole cohort (P<0.001), which was significant in both sexes (P<0.001) and in all selected age groups (P<0.001-0.03). There was a significant SUV-grade correlation for the right upper and left lower lobes, as well as for the central location in the right lung (P<0.001, P=0.005 and P=0.04, respectively). Moreover, a significant SUV-grade correlation was found for squamous cell cancer and adenocarcinoma (P<0.001 and P=0.01, respectively), and for T1-T3 factors (P<0.001, P=0.006, P=0.005 respectively). In patients with resectable lung cancer, a significant correlation was observed between the SUV of the primary tumor and its grade. This correlation was maintained for both sexes, age groups, most common histological types and T factors T1-T3.

BTN2A2, a new biomarker and therapeutic target for glioma.

Protein casein 2A2 (BTN2A2) is a costimulatory molecule first identified in antigen-presenting cells. Studies have shown the involvement of BTN2A2 in immunity. However, the exact role and the mechanism of BTN2A2 in tumors are still unclear. First, we performed real-time PCR to measure BTN2A2 expression in glioma cell lines. Next, we performed Genes Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to understand the mechanism of BTN2A2 in glioma. Next, we used the "ESTIMATE", "ssGSEA" and "CIBERSORT" algorithms to analyze the correlation between BTN2A2 and immune cell infiltration (ICI). Finally, we performed immunohistochemistry, growth curve, transwell, and colony formation assays to determine the functions of BTN2A2 in glioma. Our results showed an increase in BTN2A2 expression levels in glioma tissues and cells. Next, we determined that BTN2A2 was correlated with the prognosis of patients with glioma. Then, using the ESTIMATE, ssGSEA, and CIBERSORT algorithms, we discovered that BTN2A2 was significantly associated with immune cell infiltration (ICI) in glioma. We observed an increase in BTN2A2 expression levels with an increase in the patient's tumor grade. Furthermore, BTN2A2 significantly enhanced the proliferative and migratory abilities of glioma cells. Our results showed a significant increase in BTN2A2 expression levels in glioma cells and tissues. Furthermore, the prognosis of patients expressing high BTN2A2 levels was poor. Moreover, BTN2A2 was correlated with progression and ICI in patients with glioma. Together, this indicates that BTN2A2 could be a therapeutic target for patients with glioma.

Accurate non-invasive grading of nonfunctional pancreatic neuroendocrine tumors with a CT derived radiomics signature

PurposeThe purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs). Materials and methodsA retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference. ResultsA total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3–85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71–0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7–95.3) and 73.3% (95% CI: 62.9–83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001). ConclusionNon-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making.

Pancreatic neuroendocrine tumor: prediction of tumor grades by radiomics models based on ultrasound images.

We aimed to investigate whether the radiomics analysis based on B-mode ultrasound (BMUS) images could predict histopathological tumor grades in pancreatic neuroendocrine tumors (pNETs). A total of 64 patients with surgery and histopathologically confirmed pNETs were retrospectively included (34 male and 30 female, mean age 52.4 ± 12.2 years). Patients were divided into training cohort (n = 44) and validation cohort (n = 20). All pNETs were classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity according to WHO 2017 criteria. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator were used for feature selection. Receiver operating characteristic curve analysis was used to evaluate the model performance. Finally, 18 G1 pNETs, 35 G2 pNETs, and 11 G3 pNETs patients were included. The radiomic score derived from BMUS images to predict G2/G3 from G1 displayed a good performance with an area under the receiver operating characteristic curve of 0.844 in the training cohort, and 0.833 in the testing cohort. The radiomic score achieved an accuracy of 81.8% in the training cohort and 80.0% in the testing cohort, a sensitivity of 0.750 and 0.786, a specificity of 0.833 and 0.833 in the training/testing cohorts. Clinical benefit of the score also exhibited superior usefulness of the radiomic score, as shown by the decision curve analysis. Radiomic data constructed from BMUS images have the potential for predicting histopathological tumor grades in patients with pNETs. The radiomic model constructed from BMUS images has the potential for predicting histopathological tumor grades and Ki-67 proliferation indexes in patients with pNETs.

Mining of clinical and prognosis related genes in the tumor microenvironment of endometrial cancer: A field synopsis of observational study.

Endometrial cancer (EC) is the sixth most common malignant tumor in women worldwide, and its morbidity and mortality are on the rise. The purpose of this study was to explore potential tumor microenvironment (TME)-related biomarkers associated with the clinical features and prognosis of EC. The Estimating Stromal and Immune Cells in Malignancy Using Expression Data (ESTIMATE) algorithm was used to calculate TME immune and stromal scores of EC samples and to analyze the relationship between immune/stromal scores, clinical features, and prognosis. Heat maps and Venn maps were used to screen for differentially expressed genes (DEGs). The ESTIMATE algorithm revealed immune score was significantly correlated with overall survival and tumor grade in patients with EC. A total of 1448 DEGs were screened, of which 387 were intersecting genes. Gene Ontology (GO) analysis revealed that the biological processes (BP) related to intersecting genes mainly included T cell activation and regulation of lymphocyte activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the intersecting genes were closely related to immune-related signaling pathways. Thirty core genes with more than 7 nodes were identified using protein-protein interaction (PPI) analysis. Six independent prognostic genes of EC were identified using Kaplan-Meier survival analysis and multivariate Cox analysis, namely CD5, BATF, CACNA2D2, LTA, CD52, and NOL4, which are all immune-infiltrating genes that are closely related to clinical features. The current study identified 6 key genes closely related to immune infiltration in the TME of EC that predict clinical outcomes, which may provide new insights into novel prognostic biomarkers and immunotherapy for patients with EC.

The role of diffusion magnetic resonance imaging in determining tumor aggressiveness during preoperative surgical planning in early-stage endometrial cancer.

The present study aimed to evaluate the relationship between tumor volume and apparent diffusion coefficient (ADC) in preoperative magnetic resonance imaging and deep myometrial invasion, tumor grade, and lymphovascular space invasion (LVSI) in patients with early-stage endometrial cancer. The study included 73patients diagnosed with early-stage endometrial cancer based on histopathological examination between May 2014 and July 2019. Receiver operating characteristic (ROC) curve analysis was used to estimate the accuracy of ADC and tumor volume in predicting the LVSI, the depth of myometrial invasion (DMI), and the histopathological tumor grade in these patients. The areas under the ROC curves (AUCs) of ADC and tumor volume in predicting LVI, DMI, and high tumor grade were significantly greater than those for superficial myometrial invasion and low-grade tumors. The ROC analysis revealed that higher tumor volume was significantly associated with the prediction of DMI and tumor grade (p = 0.002 and p = 0.015). The corresponding cut-off values of tumor volume were > 7.12 and > 9.38 mL. The sensitivity of ADC in predicting DMI was higher than its sensitivity in predicting LVSI and grade1 tumors. Furthermore, tumor volume was significantly associated with the prediction of DMI and tumor grade. In the absence of pathological pelvic lymph nodes in early-stage endometrial cancer, tumor volume in DWI sequences determines the active tumor load and tumor aggressiveness. Furthermore, alow ADC indicates deep myometrial invasion and helps differentiate stage IA and stage IB tumors.

Time-trends in liver cancer incidence and mortality rates in the U.S. from 1975 to 2017: a study based on the Surveillance, Epidemiology, and End Results database.

A previous study has examined the overall cancer statistics. However, more detailed statistics regarding liver cancer have not been provided. We evaluated the incidence and mortality trends of liver and intrahepatic bile duct cancer in the United States from 1975 to 2017 based on the data in the Surveillance, Epidemiology, and End Results (SEER) database. Age, gender, race, metastasis, tumor site, and tumor grade of patients were extracted from the SEER database. Codes C22.0 and C22.1 of the International Classification of Disease for Oncology were applied to identify patients with hepatocellular carcinoma (HCC) and/or intrahepatic cholangiocarcinoma (ICC). Age-specified incidence, age-standardized incidence and mortality, 5-year relative survival, race-specific accumulative incidence and mortality, and geographic-specific accumulative mortality were calculated in different groups. Changes in trends of liver cancer incidence and mortality were assessed using Joinpoint regression. The overall incidence increased significantly from 2.641/100,000 person-years in 1975 to 8.657/100,000 person-years in 2017 [average annual percent change (AAPC) =3.42, 95% confidence interval (CI): 3.28-3.62, P<0.001]. The steepest incidence rate increase was observed in the 60-69-year-old age group (AAPC =4.40, 95% CI: 4.10-4.70, P<0.001). Males exhibited a more rapid increase in cancer incidence, from 3.928/100,000 to 13.128/100,000 person-years (AAPC =3.41, 95% CI: 3.21-3.61, P<0.001), than females [from 1.642/100,000 to 4.783/100,000 person-years (AAPC =3.03, 95% CI: 2.91-3.21, P=0.001)]. The overall mortality rate increased from 2.808/100,000 person-years in 1975 to 6.648/100,000 person-years in 2017 (AAPC =2.41, 95% CI: 2.29-2.51, P<0.001). The highest mortality rate was observed in Hawaii (6.996/100,000 person-years). The incidence and mortality rates of HCC and ICC increased from 1975 to 2017, especially in males, non-Hispanic Blacks and older individuals. Comprehensive policy and control measures should be implemented to reduce the burden of disease, particularly through health monitoring and intervention for high-risk groups.

Analysis of p21 Expression in Cervical Carcinoma at a Tertiary Institution in Ghana: An Immunohistochemical Study

Abstract Background: Cervical cancer is one of the leading causes of female mortality worldwide. About 85% occur in low-income countries with 13.8% incidence and 14% death in Ghana. p21 has been overexpressed in many cancers. Its overexpression in cervical cancer is linked to tumor growth and a bad prognosis. Aim: The expression profile of p21 in our setting is largely unknown, therefore, the necessity to evaluate p21 expression in cervical cancer. Materials and Methods: A retrospective and descriptive study design was employed to investigate p21 expression in association with demographic and clinicopathological features on formalin-fixed paraffin-embedded cervical cancer tissues. The age, histologic type, and tumor grade of patients were abstracted from the hospital records between January 1, 2015, and December 31, 2016. Tissue microarray of suitable blocks was constructed, and immunohistochemistry was performed. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 26. Results: One hundred and thirty-five cases were used for the study with an age range of 31–115 years and mean age of 58.93 years (standard deviation ± 17.88). Majority of the cases were postmenopausal (40–59 years). Squamous cell carcinoma (SCC) was the most common histological type (96.3%) with the nonkeratinizing variant having the highest frequency (53.1%). Majority of the cases were high grade; Grade 2 (33.3%) and Grade 3 (49.6%). Majority of the cases (66.7%) stained positive for p21 antibody. The associations between p21 and the clinicopathological characteristics were not statistically significant (P &gt; 0.05). p21 was more overexpressed in SCC (64.8%) than adenocarcinoma. Conclusion: An overexpression of p21 in this study suggests that it may contribute to antiapoptosis in cervical cancer leading to tumor progression, aggressive behavior, and poor prognosis.

Comprehensive Analyses of Prognostic Values and Immune Infiltration of KDM3 Gene Family inHepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancy globally with a pessimistic prognosis. Previous studies have demonstrated that abnormal expression of genes in the lysine-specific histone demethylase 3 (KDM3) family with epigenetic changes and dysregulation of enzymes promotes cancer progression. In this study, multiomics analyses were utilized to analyze differential expression, prognostic value, genetic alteration, protein-protein interaction, associated biological pathways and immune cell infiltration of KDM3s in patients with HCC. KDM3A-C were significantly upregulated to different extents based on pathologic and tumor grades in patients with HCC compared to normal tissue. Of note, higher KDM3A expression was associated with poor survival in HCC patients, whereas KDM3B and KDM3C were not associated with survival. Furthermore, KDM3A-B genetic alterations had significant effects on survival in patients with HCC. Analyses of the KEGG pathway and miRNAs targets of KDM3A and KDM3B in HCC may provide potential value in tumor behaviors and treatment. The differential expression of the KDM3 family has a strongly significant correlation with the infiltration of the abundance of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. This study indicates that KDM3A may have the potential to be a promising molecular target in terms of prognostic biomarkers or therapeutic targets for HCC treatment.

The utility of diffusion-weighted T2 mapping for the prediction of histological tumor grade in patients with head and neck squamous cell carcinoma.

BackgroundIn head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor histological grade in patients with head and neck squamous cell carcinoma (SCC).MethodsThe cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI).ResultsADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of DW-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82.ConclusionsDW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.

The vaginal microbiome is associated with endometrial cancer grade and histology.

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.

Type I IFN stimulates IFI16-mediated aromatase expression in adipocytes that promotes E2-dependent growth of ER-positive breast cancer

Although type I interferons (IFNs) play multifaceted roles during tumorigenesis and cancer treatment, the interplay between type I IFNs and estrogen signaling in breast cancer (BC) microenvironment is not well understood. Here, we report a novel function of type I IFNs in inducing aromatase expression in adipose tissues surrounding BC, which potentiates the E2-dependent growth of estrogen receptor (ER)-positive BC. First, we found that expression levels of type I IFNs correlate negatively with clinical outcome but positively with tumor grade in patients with ER-positive BC. Levels of type I IFNs were elevated in cocultured media of immune cells and BC cells, which increased aromatase expression and E2 production in Simpson–Golabi–Behmel syndrome preadipocytes. The type I IFN-induced aromatase expression was dependent on IFN-γ-inducible protein 16 (IFI16), which is encoded by an interferon-stimulated gene. At the molecular level, type I IFNs led to recruitment of HIF1α–IFI16–PRMT2 complex to the hypoxia-response element located in the aromatase PI.3/PII promoter. Next, we generated an adipocyte-specific Ifi204, which is a mouse ortholog of human IFI16, knockout mouse (Ifi204-AKO). IFNβ induced E2 production in the preadipocytes isolated from the control mice, but such E2 production was far lower in the Ifi204-AKO preadipocytes. Importantly, the growth of orthotopically inoculated E0771 ER-positive mammary tumors was reduced significantly in the Ifi204-AKO mice. Taken together, our findings provide novel insights into the crosstalk between type I IFNs and estrogen signaling in the progression of ER-positive BC.

The oncogenic role of tubulin alpha-1c chain in human tumours

Tubulin alpha-1c chain (TUBA1C), a subtype of α-tubulin, has been shown to be involved in cell proliferation and cell cycle progression in several cancers and to influence cancer development and prognosis. However, a pancancer analysis of TUBA1C to reveal its immunological and prognostic roles has not been performed. In this study, we first downloaded raw data on TUBA1C expression in cancers from The Cancer Genome Atlas (TCGA) database and multiple other databases and analysed these data with R software to investigate the prognostic and immunological value of TUBA1C in cancers. Immunohistochemical analysis was performed in gliomas to further validate our findings. Overall, TUBA1C was overexpressed in most cancers, and overexpression of TUBA1C was linked to poor prognosis and higher tumour grade in patients. In addition, TUBA1C expression was associated with tumour mutation burden (TMB), microsatellite instability (MSI), the tumour microenvironment (TME) and the infiltration of immune cells. TUBA1C was also coexpressed with most immune-related genes and influenced immune-related pathways. Immunohistochemical analysis showed that TUBA1C expression was highest in glioblastoma (GBM) tissues, second highest in low-grade glioma (LGG) tissues and lowest in normal tissues. Our study indicated that TUBA1C might be a biomarker for predicting the immune status and prognosis of cancers, offering new ideas for cancer treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-022-09595-0.

Sex-specific changes in the expression of ER-alpha and androgen receptor with increasing tumor grade in patients with hepatocellular carcinoma

Sex-specific changes in the expression of ER-alpha and androgen receptor with increasing tumor grade in patients with hepatocellular carcinoma

Role of Genetic Variations in CDK2, CCNE1 and p27KIP1 in Prostate Cancer.

Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.