Distant Metastasis Stage Research Articles

Association between tumour-infiltrating lymphocyte-T CD8+ and programmed death-ligand 1 protein with the occurrence of metastasis in colorectal cancer patients: An observational study

Background: Tumour-infiltrating lymphocytes CD8+ (TILs CD8+) as an anticancer immune response and Programmed Death-Ligand 1 (PD-L1) as an immune checkpoint molecule expression are important in colorectal cancer (CRC) as their expression correlates with the immune status and the progression of cancer. The primary objective of this study is to examine the relationship between TILs CD8+ and PD-L1 expression levels and CRC metastasis to provide insights into the immune microenvironment’s role in CRC progression and metastasis, potentially improving patient outcomes and treatment response. Methods: This study was an observational study involving colorectal cancer patients who were treated at a tertiary hospital in Bandung, West Java, Indonesia. There were 40 patients included in the study. Tumour tissue samples were collected from patients, and immunohistochemical staining was performed to evaluate TILs CD8+ infiltration and PD-L1 expression levels. Clinical data, including metastasis occurrences, were collected from the cancer registry. Results: Analysis of TILs CD8+ and PD-L1 expression levels in CRC patients revealed significant findings regarding metastasis occurrence and cancer staging. There was a notable positive correlation between PD-L1 expression and TILs-CD8+ infiltration in the presence of distant metastasis and advanced cancer stage (p < 0.05). However, no significant association was observed between TILs CD8 and PD-L1 expression levels and lymphatic metastasis. Conclusion: This study highlights the potential prognostic value of TILs CD8+ and PD-L1 expression levels in predicting CRC progression and metastasis. However, the lack of a significant correlation with lymphatic metastasis suggests the need for further investigation into the underlying mechanisms. Understanding the roles of PD-L1 and TILs-CD8+ expression in CRC metastasis may facilitate the development of targeted therapeutic strategies to improve patient outcomes.

Association Between the Protein Expressions of MutS Homologs and Villin and the Clinicopathological Characteristics in 310 Colon Cancer Patients

To examine the relationship between the expressions of mismatch repair proteins, MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6), and villin and the pathological features in patients with colon cancer. A total of 310 cases of colon cancer patients who were treated at our hospital between January 2017 and September 2021 were selected. The diagnosis of colon cancer of all patients was verified by pathological evaluation. Immunohistochemistry was used to determine the protein expressions of MSH2, MSH6, and villin. The correlation between the expressions of MSH2, MSH6, and villin and the clinicopathological parameters in patients with colon cancer was analyzed accordingly. Multivariate logistic regression was used to analyze the correlation between the expressions of MSH2, MSH6, and villin and the clinicopathological parameters of colon cancer. Kaplan-Meier survival curve was used to compare the 2-year survival rates of colon cancer patients with different expression levels of the proteins. Among the 310 patients with colon cancer, the negative expression rates of MSH2, MSH6, and villin proteins in cancer tissues were 8.71% (27/310), 9.35% (29/310), and 46.13% (143/310), respectively. The negative expression rates of the three proteins in tissues adjacent to cancer were 3.23% (10/310), 4.19% (13/310), and 9.68% (30/310), respectively. The negative expression rates of the three proteins in cancer tissues were all higher than those in adjacent tissues (P<0.05). Regression analysis showed that the expression of MSH2 and MSH6 in cancer tissues was correlated with the age, the location of tumor lesions, tumor differentiation degree, and lymph node metastasis in colon cancer patients (P<0.05). The expression of villin in the cancer tissue is correlated with the depth of tumor infiltration, lymph node metastasis, distant metastasis, and clinical staging status in colon cancer patients (P<0.05). The 2-year survival rates of patients with negative expressions of MSH2 and MSH6 were 51.85% and 44.83%, respectively, which were lower than those of patients with positive expression of MSH2 and MSH6 (79.51% and 80.43%, P<0.05). Thirteen patients (4.1%) had negative expression of MSH2, MSH6, and villin (referred to as "triple negative expressions") in the cancer tissues, and their 2-year survival rate was 30.77%, which was lower than that of colon cancer patients who did not meet the criteria for triple negative expressions (79.12% [235/297], P<0.05). The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.

Non-Hodgkin lymphoma incidence, mortality, and survival trends in Brunei Darussalam from 2011 to 2020

BackgroundNon-Hodgkin lymphoma (NHL) has been identified as a significant contributor to the cancer burden. This study investigates the incidence, mortality, and survival trends of NHL cancer in Brunei Darussalam from 2011 to 2020.MethodsThis is a registry-based retrospective study using de-identified data from the Brunei Darussalam Cancer Registry on patients diagnosed with NHL from 2011 to 2020 based on the ICD-10 codes C82-86. Statistical methods include descriptive statistics, age-specific and age-standardised incidence (ASIR) and mortality rates (ASMR), and joinpoint regression for trend analysis. Survival analysis was conducted using Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards regression.ResultsFrom 2011 to 2020, 330 patients were diagnosed with NHL. The majority of patients were males (51.8%) and of Malay descent (82.7%). The age group most diagnosed was 55–74 years (42.3%), with a mean age at diagnosis being 55.1 years. The ASIRs were 12.12 for males and 10.39 per 100,000 for females; ASMRs were 6.11 for males and 4.76 per 100,000 for females. Diffuse large B-cell lymphoma was the most prevalent subtype, accounting for 39.1% of cases. The overall 5-year survival rate was 61.2%, with lower rates observed in older patients and those diagnosed at distant metastasis stage. Furthermore, older age and advanced stage diagnosis significantly increased mortality risk. NHL incidence and mortality rates in Brunei Darussalam remain stable over the period of 10 years, but highlights significant disparities in gender and age.ConclusionsThe findings emphasize the importance of early detection and tailored treatments, especially for high-risk groups, in managing NHL’s burden. These insights underline the need for focused healthcare strategies and continued research to address NHL’s challenges.

CTSG may inhibit disease progression in HIV-related lung cancer patients by affecting immunosuppression

ObjectivesLung cancer is an independent risk factor for pulmonary complications following HIV infection. This study aimed to examine the expression and clinical significance of Cathepsin G (CTSG) protein in both non-HIV and HIV-related lung cancers.MethodsThe data related to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) in the TCGA dataset and the data related to healthy individuals in the GTEx dataset, the GEPIA2 database was used to excavate the distinction in the expression of CTSG protein in non-small cell lung cancer (NSCLC) tissues versus normal non-cancerous tissues. The Ualcan database was used to compare the differences in CTSG expression at different stages of LUAD and LUSC. Immunohistochemistry (IHC) was used to detect the expression of CTSG proteins in the pathological tissues of patients with HIV-related lung cancer and patients with lung cancer without co-infection, the Kaplan-Meier method was used for survival analysis.ResultsWe observed that CTSG expression in NSCLC is lower compared to adjacent non-tumor tissues and correlates with NSCLC clinical stage. CTSG protein expression in HIV-related lung cancer tissues was lower than in adjacent tissues and lower than in lung cancer tissues without HIV infection, with a statistically significant difference (P < 0.05). It correlated with CD4 + T cell count and CD4+/CD8 + T cell ratio, as well as with the pathological type, distant metastasis, and clinical stage of HIV-related lung cancer, all with statistical significance (P < 0.05).ConclusionsCTSG could potentially mitigate disease advancement in HIV-related lung cancer patients by inhibiting immune depletion, serving as a prospective immunotherapeutic target for both non-HIV and HIV-associated lung cancers.

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Descriptive epidemiology of prostate cancer in India, 2012-2019: Insights from the National Cancer Registry Programme.

This study describes the epidemiology, clinical extent at diagnosis, and treatment modalities for prostate cancer in India. This study is a secondary analysis of primary prostate cancer data sourced from the National Cancer Registry Programme. Data from population-based cancer registry for the period 2012-2016 were used to estimate the incidence rates, including crude incidence rate (CR), age-adjusted incidence rate (AAR), age-specific rate, and cumulative risk. Trends in the AAR were assessed using join-point regression. Hospital-Based Cancer Registry data from 2012 to 2019 were used to describe the clinical extent of the cancer at diagnosis and the treatment modalities. The incidence of prostate cancers was higher in urban registries such as Delhi, Kamrup Urban, and Mumbai (AAR of 11.8 per 100,000, 10.9 per 100,000, and 9.7 per 100,000, respectively). Prostate cancer incidence showed a rise after the age of 50, with a notable acceleration after age 64. The overall annual percentage change for prostate cancer incidence from 1982 to 2016 was 2.6. Around 43.0% of all prostate cancers were diagnosed at the distant metastatic stage. Surgery and radiotherapy, either as standalone treatments or in combination with other modalities, contributed to the treatment of 78.5% of localized cancer, 74.2% of locoregional cancer, and 57.2% of distant metastatic stage of prostate cancer. There is heterogeneity in the incidence of prostate cancer, as evidenced by urban registries. Additionally, there is a need for downstaging the disease, without risking overdiagnosis.

Identification of KRT80 as a Novel Prognostic and Predictive Biomarker of Human Lung Adenocarcinoma via Bioinformatics Approaches.

According to the 2022 Global Cancer Statistics, lung cancer is the leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (LUAD), which is a histological subtype of Non- Small Cell Lung Cancer (NSCLC), accounts for 40% of primary lung cancer. Therefore, there is an urgent need to identify new prognostic markers as clinical predictive markers for LUAD. This study aimed to investigate the role of Keratin 80 (KRT80) in the prognosis of LUAD and its underlying mechanisms. Bioinformatics analysis was conducted using data retrieved from The Cancer Genome Atlas (TCGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed to predict the involved biological processes and signaling pathways, respectively. The LinkedOmics database was utilized to identify differentially expressed genes (DEGs) correlated with KRT80. Nomograms and Kaplan-Meier plots were constructed to evaluate the survival outcomes of patients diagnosed with LUAD. Moreover, TIMER was employed to conduct correlation analyses between KRT80 expression and immune cell infiltration, shedding light on the intricate interplay between KRT80 and the tumor microenvironment in LUAD. To ascertain the RNA and protein expression levels of KRT80 in LUAD and adjacent normal tissues, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry techniques were employed, respectively. Scrutiny of the TCGA dataset revealed KRT80 up-regulation across pan-cancer tissues, notably elevated in LUAD compared to healthy lung tissues. This finding was validated in our clinical samples, where Kaplan-Meier survival curves indicated poorer survival rates for high KRT80 expression in LUAD. A positive correlation was found between the transcription level of KRT80 in LUAD samples and clinical parameters, such as lymph node metastasis stage, distant metastasis, and pathological stage. Survival, logistic regression, and Cox regression analyses emphasized the clinical prognostic significance of high KRT80 expression in LUAD. Nomogram results underscored the robust predictive potential of KRT80 for the survival of LUAD patients. Gene functional enrichment analyses mainly associated KRT80 with cytokine-cytokine receptor interactions, cell cycle, apoptosis, and chemokine signaling pathways. Based on the results of the immune infiltration analysis, it can be found that the expression of KRT80 is related to the immune cell subsets and survival rate of patients with LUAD. Our research revealed a significant upregulation of KRT80 in LUAD, with heightened KRT80 expression correlating with unfavorable prognosis. This study represents a comprehensive and systematic evaluation of KRT80 expression in LUAD, encompassing its prognostic and diagnostic significance, as well as underlying mechanisms. Our findings suggest that KRT80 may emerge as a novel prognostic and predictive biomarker in LUAD.

Precision medicine for papillary thyroid carcinoma (PTC) variants: A machine learning approach to prognosis and treatment guidance.

e18072 Background: PTC is a common endocrine cancer with a good prognosis, but aggressive subtypes, such as Hürthle cell (HCC) and columnar cell variants (CCV), pose challenges due to their higher recurrence and metastasis rates. To provide personalized care, we applied machine learning to evaluate the treatment effectiveness and develop precise prognostic models for PTC variants. Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or with other concurrent malignancies, and unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 3690 patients. Among them 3180 patients with CCV and 510 patients with HCC, respectively. Most patients (62.8%) were 45 years or older, with a median age of 52 years. A total of 56.9% of patients had a tumor size greater than 2 cm, with a median tumor size of 3.1 cm. The largest racial group was white, comprising 83.8% of the cases, and 11.8% of the cases were Asian. Most cases were regional (53.4%, n=1969), followed by localized (38.3%, n= 1413). Multivariate Cox regression analysis revealed that N1 negatively affected the survival of HCC patients. CCV has a favorable prognosis after surgery, radiotherapy, or total thyroidectomy. Poor prognosis in CCV is associated with black race, large tumor size, and T4 stage. Improved survival in the localized/regional stage and decreased survival with male sex, older age, distant metastasis, and advanced AJCC stage in both PTC subtypes. ML models revealed that the random forest classifier (RFC) and K-Nearest Neighbors (KNN) accurately predicted outcomes, followed by Logistic Regression (LR) models. The highest contributing factors were AJCC staging, tumor size, and T aspect of TNM staging. Conclusions: Our study offers a method for evaluating and treating patients with PTC variants. The machine learning model that we created serves as a useful and personalized resource to aid in clinical decision-making processes.[Table: see text]

Upregulation of NPC1 and its association with poor prognosis in gastric cancer.

The Niemann-Pick disease type C1 (NPC1) protein plays a pivotal role in lipid transport, particularly free cholesterol, within lysosomal/late endosomal membranes. Previous studies have highlighted NPC1 as a promising target for cholesterol trafficking and cancer therapy. Nevertheless, the expression of NPC1 in gastric cancer (GC) and its clinical implications remain unexplored. This study aims to investigate NPC1 expression in GC and its correlation with patient prognosis. NPC1 expression levels in GC and normal tissues were assessed using the GEPIA database, and survival analysis was conducted via Kaplan‒Meier Plotter. Evaluation of potential biological effects of NPC1 in GC by protein-protein interaction network and GO, KEGG bioenrichment analysis. Immunohistochemistry was performed on surgical samples collected from 306 GC patients. Correlations between NPC1 expression, clinical characteristics, and patient prognosis were analyzed. NPC1 mRNA expression was elevated in GC tissues compared to normal tissues (P < 0.05) and significantly associated with poorer prognosis. In our cohort of 306 patients, NPC1 exhibited significant upregulation in GC versus adjacent normal tissues (P = 0.031). High NPC1 expression correlated with adverse clinical characteristics, including lymph node metastasis, distant metastasis, and advanced TNM stage (all P < 0.05). Patients with high NPC1 expression experienced notably shorter overall survival (P < 0.001), particularly in stages III and IV (P = 0.003). Multivariate Cox regression analysis identified high NPC1 expression as an independent prognostic factor for GC patients (HR 1.57, 95% CI 1.14-2.18, P = 0.006). Lastly, an optimized nomogram incorporating NPC1, tumor size, and TNM stage was constructed. NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.

CD146 Promotes EMT-Mediated Migration and Invasion of NSCLC via PI3K/Akt Signaling Pathway.

Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

Immature central tumor tertiary lymphoid structures are associated with better prognosis in non-small cell lung cancer

Background & aimsTertiary lymphoid structures (TLSs) are predictive biomarkers of favorable clinical outcomes and immunotherapy response in several solid malignancies, including non-small cell lung cancer (NSCLC). However, the relationship between TLSs and NSCLC prognosis has not been eludicated from the aspects of location, density, and maturity. This study aimed to investigate the clinicopathological and prognostic significance of TLSs in NSCLC.MethodsA collection of 151 resected pulmonary nodules in patients with NSCLC was retrospectively analyzed. Two experienced pathologists reviewed hematoxylin-eosin (H&E) slides and assessed TLS scores at different anatomic subregions. Then, we analyzed their correlation with clinicopathologic parameters and CD8 staining intensity and assessed multiple clinicopathological factors affecting patient prognosis.ResultsCD8 expression was correlated with total (TLS-CT) (P = 0.000), aggregates (Agg) (TLS-CT) (P = 0.001), follicles (FOL)-I (TLS-CT) (P = 0.025), and TLS(overall) (P = 0.013). TLS scores in the central tumor (CT) and invasion margin (IM) areas were negatively correlated with distant metastasis and Union for International Cancer Control (UICC) stage in NSCLC patients, while TLS score in the CT area was positively correlated with CD8 expression. TLS (overall), Agg (TLS-CT), and FOL-I (TLS-CT) were positively correlated with distant metastasis, UICC stage, and CD8 expression in NSCLC patients. Agg (TLS-IM) was positively correlated with distant metastasis and UICC stage. FOL-I (TLS-IM) was positively correlated with UICC stage. FOL-II (TLS-IM) was positively correlated with distant metastasis (P < 0.05). Multivariate Cox regression analysis showed that unfavorable independent prognostic factors were associated with metastasis status and UICC stage. Independent prognostic factors with protective effects included Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS (P < 0.05).ConclusionHistological score assessment of H&E sections of Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS levels in NSCLC has prognostic value.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Effectiveness and safety of darolutamide as a component of combination therapy in patients with prostate cancer

Prostate cancer is an extremely important problem in current urologic oncology. For a long time, the golden standard of treatment of common forms of prostate cancer at the stage of distant metastases was androgen deprivation therapy directed at suppression of native testosterone level. Combination treatment using long-term androgen deprivation therapy and new generation antiandrogens is currently a scientifically substantiated conceptually new standard of therapy which has replaced treatment paradigm using androgen deprivation therapy as a monotherapy in patients with metastatic hormone-sensitive prostate cancer. The article presents the results of large trials performed in patients with metastatic hormone-sensitive prostate cancer and characterizes the role of one of the most effective and safe drugs, darolutamide, used to treat patients of this subgroup.

FOXN2, identified as a novel biomarker in serum, modulates the transforming growth factor-beta signaling pathway through its interaction with partitioning defective 6 homolog alpha, contributing to the pathogenesis of gastric cancer

Background and Objective Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC. Methods Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis. Results FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFβ) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A). Conclusion In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFβ pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.

PDLIM7 Promotes Tumor Metastasis in Papillary Thyroid Carcinoma via Stabilizing Focal Adhesion Kinase Protein.

Background: As an actin cytoskeleton interactor, PDZ (postsynaptic density 65-discs large-zonula occludens 1) and LIM (abnormal cell lineage 11-isket 1-mechanosensory abnormal 3) domain protein 7 (PDLIM7) was supposed to play an essential role modulating cytoskeleton. Focal adhesions (FAs), which are located at the cytomembrane terminus of actin cytoskeleton, function as a force sensor and can transform the mechanical signal to a biochemical signal. Focal adhesion kinase (FAK) localizes to and regulates signal transduction in FAs, which play an essential role in cell polarity, migration, and invasion. However, whether PDLIM7 is involved in FAs-associated signal transduction and its role in tumor invasion and metastasis remains largely unknown. Methods: A cohort of 80 patients with papillary thyroid carcinoma (PTC) at The Second Affiliated Hospital of Guilin Medical University, as well as 512 PTC samples from The Cancer Genome Atlas thyroid cancer database was utilized to analyze the expression of PDLIM7 and its association with prognosis. Survival data were assessed using Kaplan-Meier curves, whereas clinicopathological characteristics such as age, sex, tumor size, multilocality, extrathyroidal extension, lymph metastases, Hashimoto's thyroiditis, distant metastasis, and TNM stage were considered. Functional assays were performed in vitro and in a xenograft mouse model to assess the role of PDLIM7 in PTC cell lines. The colocalization of PDLIM7 with FAK and integrin alpha V (ITGAV) was determined using immunofluorescence assay and immunoprecipitation assay. Protein expression levels in cell and tissue biopsies were measured through Western blotting and immunohistochemistry. Results: (1) The PDLIM7 protein frequently upregulated in both PTC tissues and cells, and overexpression of PDLIM7 is associated with advanced clinicopathological characteristics. (2) Knockdown of PDLIM7 effectively inhibits cell proliferation, migration, and invasion in PTC cell lines in vitro. (3) Knockdown of PDLIM7 hinders the growth and metastasis of TPC-1 xenografts in vivo. (4) PDLIM7 demonstrates colocalization with both FAK and the FA molecule ITGAV and the knockdown of PDLIM7 resulted in disassembly of FAs and proteosome-dependent degradation of FAK in PTC cell lines. Conclusions: PDLIM7 function as an oncoprotein in PTC to promote metastasis, and a novel underlying mechanism is proposed that PDLIM7 keeps FAK protein from proteosome-dependent degradation.

Predictors of PSMA positivity at initial staging of prostate cancer.

283 Background: PSMA-based imaging improves detection of metastatic disease for initial staging of men diagnosed with prostate cancer (PCa) with higher accuracy compared to conventional imaging. PSMA imaging is now being increasingly adopted for initial local and distant metastatic staging. We sought to determine the contribution of clinical and pathological factors associated with PSMA positive nodal or metastatic disease. Methods: We retrospectively identified 404 men diagnosed with PCa who underwent initial staging with Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT across our eleven-hospital system from July 2021-December 2022. Patient characteristics, including demographic, clinical, pathologic, and imaging variables were obtained. PSMA positivity representing a suspicious nodal or distant lesion was determined based on radiology reports, histopathology, and other imaging modalities, and equivocal or likely benign lesions were counted as negative. Patients with prior diagnosis (&gt;6 months) of PCa (n=42) or incomplete clinical history (n=22) were excluded. Clinical variables were compared with Wilcoxon Rank Test, Chi square, and Fishers’ exact test as well as univariable and multivariable logistic regression. Number of risk factors for patients with unfavorable intermediate or very high risk disease was also examined. PSA was log transformed. Statistical significance was defined as p&lt;0.05. Results: 103/340 patients (30.3%) had PSMA imaging findings concerning for nodal or distant metastatic disease. Patients with positive finding were less likely to be Black, and had higher PSA, biopsy Gleason Grade Group, and higher presumptive NCCN risk. Stratifying by pre-scan NCCN risk group, PSMA positivity was observed in no patients with favorable intermediate risk PCa (n=17), 9.8% (12/123) with unfavorable intermediate risk PCa, 29% (25/86) with high risk PCa, and 58% (66/114) with very high risk PCa. Stratifying by number of risk factors, there were significant differences in scan positivity comparing unfavorable intermediate risk disease with 1 vs ≥2 risk factors (4.2% vs 17%, p=0.03) and very high risk disease with 1 risk vs ≥2 risk factors (49% vs 72%, p=0.01). On multivariable analysis, NCCN classification stratified by risk factors was associated with PSMA positivity while Black race was inversely associated (OR 0.32, 95% CI 0.11, 0.82, p=0.03). Conclusions: Initial staging with PSMA PET/CT identified local regional or metastatic disease in 30% of PCa patients. A substantial proportion of unfavorable intermediate risk men were N1 or M1 based on PSMA positivity, particularly those with multiple unfavorable intermediate risk features. The clinical benefit for PSMA PET/CT in patients with favorable intermediate risk PCa is low. Limitations include retrospective design (including possible selection bias for patients with equivocal lesions on conventional imaging) and a limited number of black men in the cohort.

Chinese expert consensus: multidisciplinary diagnosis and treatment of multiple ground-glass nodule like lung cancer (2024 edition)

Multiple ground glass nodules (GGN) like lung cancer is a special type of synchronous multiple primary lung cancer, with two or more lesions present simultaneously. It has characteristics such as"indolent"development, less lymph node or distant metastasis, identical or different pathological stages, differential driving gene mutations, diverse imaging manifestations, and good prognosis. In order to standardize the diagnosis and treatment behavior of multiple GGN-like lung cancer, reduce issues such as over diagnosis and insufficient treatment, relevant domestic experts are organized by The Lung Cancer Medical Education Committee of the Chinese Medical Education Association, Lung Cancer Alliance of Chinese Thoracic Surgery, the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Tumor Ablation Expert Committee of the Chinese Society of Clinical Oncology, the Tumor Ablation Expert Group of the Chinese College of Interventionalists, The Chinese Expert Consensus:Multidisciplinary Diagnosis and Treatment of Multiple Ground-Glass Nodule Like Lung Cancer (2024 Edition) was discussed and formulated. The main content includes: follow-up strategies, differential diagnosis, diagnosis and staging, treatment methods, and post treatment follow-up for multiple GGN-like lung cancer.

BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07)cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

ACAT2 may be a novel predictive biomarker and therapeutic target in lung adenocarcinoma.

Acyl-coenzyme A cholesterol acyltransferase (ACAT) is a membrane-binding enzyme localized in the endoplasmic reticulum. ACAT2 can promote the development of colon cancer, but its efficacy in lung adenocarcinoma (LUAD) remains uncertain. ACAT2 expression was performed by using the TIMER2.0 database. The GEPIA database was utilized to analyze the correlation between ACAT2 expression and pathological stage of the tumor. Clinical prognosis was assessed through the Kaplan-Meier analysis. The CancerSEA database was employed to scrutinize the correlations between the ACAT2 expression and the functional status of various tumors, which were subsequently visualized as a heatmap. Furthermore, molecular interaction network analysis was performed by the STRING tool. High ACAT2 expression was associated with a poor DFS and OS in LUAD patients. Cox regression analysis indicated that the poor outcomes may be related to tumor stage, nodal stage, distant metastatic stage. ACAT2 was found to play a crucial role in various biological processes, including the cell cycle, DNA repair, DNA damage response, and proliferation. Enrichment pathway analysis revealed four ACAT2 related genes, ACOX1, EHHADH, OXCT1, and DLAT. Our study showed that ACAT2 was upregulated in LUAD, and had a worse survival. ACAT2 could be a novel predictive biomarker and therapeutic target in LUAD.

IRS1 promotes thyroid cancer metastasis through EMT and PI3K/AKT pathways.

Insulin receptor substract 1 (IRS1) protein is an important signal transduction adapter for extracellular signal transduction from insulin-like growth factor-1 receptor and its family members to IRS1 downstream proteins. IRS1 has been reported to be involved in tumourigenesis and metastasis in some of solid tumors. Investigating the role of IRS1 in thyroid cancer can help to screen high risk patients at the initial diagnosis. Immunohistochemical assay was used to detect the expression levels of IRS1 in 131 metastatic thyroid cancer tissues. Wound healing, cell invasion and colony formation assays were used to study the functions of IRS1 in vitro. RNA sequencing (RNA-seq) and Western blot analysis analyses were performed to examine the underlying regulation mechanisms of IRS1 in thyroid cancer cells. IRS1 was highly expressed in thyroid cancers and its expression was positively associated with distant metastasis and advanced clinical stages. In vitro studies demonstrated that IRS1 is an important mediator of migration, invasion and colony formation of thyroid cancer cells. RNA-seq showed that IRS1 promoted the metastasis of thyroid cancer by regulating epithelial-mesenchymal transition and phosphoinositide 3-kinase (PI3K)/AKT pathway. IRS1 overexpression contributes to the aggressiveness of thyroid cancer and is expected to be a stratified marker and a potential therapeutic target for thyroid cancer.