NLRP3 is Highly Expressed in Stomach Adenocarcinoma and May Serve as a Novel Prognostic Biomarker

Background: Stomach adenocarcinoma (STAD) is a common cancer type around the world. The prognosis in advanced patients is poor. Since NLRP3 was not extensively studied in the field of tumor, so we aimed to identify the impact of NLRP3 on STAD by bioinformatics analyses and in vitro experiments. Methods: TCGA , kaplan-Meier Plotter and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of gastric carcinoma patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Finally, we verified the NLRP3 expression in paired gastric cancer tissues and adjacent normal tissues by western blot and q-PCR. We also constructed NLRP3 overexpression model in gastric cancer cell line and observed cell proliferation ability.Results: NLRP3 expressed disparately in gastric tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for bad prognosis in STAD. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with unfavorable clinicopathologic parameters such as higher T stage, higher histologic grade and worse survival outcome. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with poor prognosis, unfavorable clinicopathologic parameters and increased proportion of immune cells in STAD. In vitro analysis revealed that cell proliferation ability was enhanced in gastric cancer cells trasnfected with NLRP3 overexpression. These conclusions indicate that NLRP3 has great potential to serve as a biomarker for evaluating prognosis in patients diagnosed with gastric carcinoma.

On the Road to Accurate Protein Biomarkers in Prostate Cancer Diagnosis and Prognosis: Current Status and Future Advances

Prostate cancer (PC) is a leading cause of morbidity and mortality among men worldwide. Molecular biomarkers work in conjunction with existing clinicopathologic tools to help physicians decide who to biopsy, re-biopsy, treat, or re-treat. The past decade has witnessed the commercialization of multiple PC protein biomarkers with improved performance, remarkable progress in proteomic technologies for global discovery and targeted validation of novel protein biomarkers from clinical specimens, and the emergence of novel, promising PC protein biomarkers. In this review, we summarize these advances and discuss the challenges and potential solutions for identifying and validating clinically useful protein biomarkers in PC diagnosis and prognosis. The identification of multi-protein biomarkers with high sensitivity and specificity, as well as their integration with clinicopathologic parameters, imaging, and other molecular biomarkers, bodes well for optimal personalized management of PC patients.

FOXC1

Context.— Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)–based surrogate molecular classification. Objective.— To investigate the diagnostic utility of the IHC-based FOXC1 test in breast cancer subtyping and to evaluate the correlation between FOXC1 expression and clinicopathologic parameters in triple-negative breast cancer (TNBC). Design.— FOXC1 expression was evaluated with IHC in a large cohort of 2443 patients with breast cancer. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of FOXC1 expression to predict the triple-negative phenotype and to identify the best cutoff value. FOXC1 expression was correlated with the clinicopathologic parameters of TNBC. Results.— The expression rate of FOXC1 in TNBC was significantly higher than in other subtypes. The area under the ROC curve confirmed the high diagnostic value of FOXC1 for the prediction of the triple-negative phenotype. The cutoff value of 1% showed a maximized sum of sensitivity and specificity. In TNBC, FOXC1 expression was significantly associated with aggressive tumor phenotypes. Furthermore, FOXC1 expression was primarily observed in invasive breast carcinoma of no special type and metaplastic carcinoma but rarely in invasive carcinoma with apocrine differentiation. Correspondingly, FOXC1 expression was significantly associated with the expression of basal markers but was negatively correlated with apocrine-related markers in TNBC. Conclusions.— In conclusion, FOXC1 is a highly specific marker for the triple-negative phenotype. Moreover, immunohistochemical detection of FOXC1 expression can be used as an additional diagnostic tool for the triple-negative phenotype and subclassification in TNBC.

Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma

BackgroundMuch importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC).MethodsPDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis.ResultsCTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P<0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043).ConclusionsOur research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.

Value of Thyroid Imaging Reporting and Data System in Initial Bethesda Category III Thyroid Nodules

Background. To evaluate the role of Thyroid Imaging Reporting and Data System (TI-RADS) in predicting malignancy for cytological Bethesda system III nodules. Method. The study included 188 thyroid nodules with first Bethesda system III cytology on surgery or repeat FNA. Patients' clinicopathologic parameters and ultrasonographic (US) nodule characteristics were evaluated according to benignity and malignancy. Using the TI-RADS classification system, thyroid nodules were categorized. Results. The size of malignant nodules was significantly lower than that of benign nodules ( P < 0.001). Thyroid nodules associated with concomitant thyroid carcinoma had a significantly increased risk of malignancy ( P < 0.001). Univariate analysis indicated that there were significant differences in the images of benign and malignant nodules in terms of solid composition, hypoechogenicity or marked hypoechogenicity, a taller-than-wide or irregular shape, ill-defined margins, and microcalcifications presence ( P < 0.05). TI-RADS categories 4c (OR = 8.3, 95% CI 3.8–18.1; P = 0.043) and 5 (OR = 9.4; 95% CI 1.2–74.2; P = 0.026) were predictive for malignancy. Conclusions. The TI-RADS US evaluation may assist the physician in deciding whether to proceed with follow-up, repeating FNA, or surgical intervention.

Correlation of Nuclear Morphometry with Clinicopathologic Parameters in Malignant Breast Aspirates

Objectives The primary objective of this study was to correlate nuclear morphometric parameters with clinicopathologic features such as cytologic grade, tumor size, lymph node status, mitotic index, and histopathologic grade. Secondary objective was to quantify nuclear changes on malignant breast aspirates using morphometry. Material and Methods Forty-five cases of carcinoma breast diagnosed on cytology were included in this study. These were graded into cytologic grades 1, 2, and 3 as per Robinson’s cytologic grading system.Nuclear morphometry was done in all cases on smears stained with Papanicolaou stain.Clinicopathologic parameters including cytological grade, tumor size, lymph node status, mitotic count, and histological grade were correlated with nuclear morphometric parameters, namely, area, perimeter, shape, long axis, short axis, intensity, long-run emphasis, total run length, and T1 homogeneity. Results There were 9 cases in cytologic grade 1, 26 in grade 2, and 10 cases in cytologic grade 3. Histopathology showed 42 cases of infiltrating duct carcinoma, not otherwise specified (IDC, NOS) and 3 cases (6.7%) of ductal carcinoma in situ (DCIS). IDC (NOS) included 6, 27, and 9 cases in grades 1, 2, and 3, respectively. Majority of our cases had a tumor size less than 5 cm (n = 38, 84.4%) and had positive nodes (n = 30, 66.7%). Correlation of cytologic and histopathologic grades (including DCIS) with all morphometric features except long-run emphasis was statistically significant. Correlation of morphometry with tumor size yielded significant results for nuclear area, perimeter, long and short axes, and intensity with p < 0.05. Study of lymph node status (positive/negative) versus morphometry showed a highly significant statistical association with all the geometric as well as textural parameters. Mitotic count was significantly associated with all the geometric parameters and one textural parameter (total run length). Statistics Continuous variables were presented as mean ± standard deviation and compared using the two-tailed, independent sample t-test and one-way analysis of variance test. Tests were performed at significance level of 0.05. Conclusion Morphometry is an objective technique which holds immense promise in prognostication in breast carcinoma.