Distant Metastasis Stage Research Articles

Deubiquitinating enzyme USP10 promotes osteosarcoma metastasis and epithelial-mesenchymal transition by stabilizing YAP1.

Osteosarcoma (OS) is a fatal adolescent tumor, which is susceptible to remote metastases at an early stage, and its treatment remains a major challenge. ubiquitin-specific protease 10 (USP10) is primarily located in the cytoplasm and can therefore deubiquitinate various cytoplasmic proteins. However, the expression and mechanism of USP10 in OS remain ambiguous. The aim of this study was to explore how USP10 affects Yes-associated protein1 (YAP1) to influence the metastasis and epithelial-mesenchymal transition (EMT). Western blotting, qRT-PCR, and immunohistochemical (IHC) analyses were performed to evaluate USP10 and YAP1 levels. Using wound healing and transwell tests, the roles and molecular pathways of USP10 and YAP1 ability to migrate and invade of OS were investigated, and cell morphological alterations were examined using phalloidin staining. Our results indicated that USP10, a new type of deubiquitinating protease, is increased in OS tissues and cells contrasted with adjacent healthy tissues. Overexpression of USP10 correlated with tumor size, distant metastasis, and TNM stage, and was an independent factor of poor prognosis in OS patients. Also, USP10 expression is closely connected with the incident of OS metastasis and tumor size. Functional assays revealed that USP10 knockdown suppressed cell migrating and invading ability and inhibited the EMT of OS cells in vivo and in vitro. In addition, we showed that USP10 knockdown decreased the levels of YAP1, which is an important positive regulator of migration and invasion in many cancers. We also found a significant positive correlation between USP10 and YAP1 levels, further demonstrating that USP10-induced migration and EMT are based on YAP1 in OS cells. In a mechanistic way, USP10 stabilizes the expression of YAP1 by mediating its deubiquitination in OS cells. Together, this study showed that USP10 can directly interact with YAP1 to reduce ubiquitinated YAP1, thereby stabilizing its protein levels and affecting EMT and distant metastasis in OS cells.

C6orf15 acts as a potential novel marker of adverse pathological features and prognosis for colon cancer.

To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207±0.694 vs 0.276±0.166, t=8.281, P<0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2=8.30, P=0.04), lymph node metastasis (χ2=36.97, P<0.001), distant metastasis (χ2=8.69, P=0.003) and pathological stage (χ2=34.17, P<0.001). High expression of C6orf15 was associated with poor prognosis (χ2=6.43, P<0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P=0.023) and lymph node metastasis (P=0.048). C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer.

The diagnostic potential of a circRNA-miRNA network in non-small cell lung cancer.

Increasing studies demonstrate the significant contributions of circRNA-related competitive endogenous RNA (ceRNA) regulatory networks to tumorigenesis and cancer progression. Here, we aimed to construct a non-small cell lung cancer (NSCLC)-specific circRNA-miRNA network and evaluate its diagnostic potential in NSCLC. MiRNA deep sequencing was performed to screen differentially-expressed serum miRNAs in NSCLC. Four bioinformatics databases (TargetScan, miRanda, starBase, and RNAhybrid) were used to analyze the integrated circRNA-miRNA interaction network. The circRNA-miRNA network, including hsa-miR-4482-3p, hsa-miR-146a-3p, hsa_circ_0008167 and hsa_circ_0003317 was constructed based on their interactions and preliminary testing in NSCLC cells. The relative levels of the selected non-coding RNAs (ncRNAs) were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) in the healthy, pneumonia, benign lung tumor and NSCLC cohorts. The diagnostic power of the circRNA-miRNA network was evaluated using receiver operating characteristic (ROC) analyses. The serum levels of hsa-miR-4482-3p, hsa-miR-146a-3p, hsa_circ_0008167, and hsa_circ_0003317 were dysregulated in NSCLC. The combination of the four ncRNAs showed the highest diagnostic value to discriminate between benign lung tumors and NSCLC. Additionally, the upregulated levels of hsa_circ_0008167 were correlated to more aggressive features of NSCLC, such as lymph node metastasis, distant metastasis, and higher stage. Furthermore, the combination of hsa_circ_0008167 + hsa-miR-4482-3p, and hsa_circ_0008167 + hsa-miR-4482-3p + hsa-miR-146a-3p had the greatest diagnostic power to differentiate between lymph node +/- metastases and higher/lower stages, respectively, compared to circRNAs or miRNAs alone, and traditional tumor markers. In conclusion, we identified a specific circRNA-miRNA network with higher sensitivity and specificity to diagnose NSCLC, thereby providing a new strategy for further development of ceRNA-related tumor markers in other cancers. KEY MESSAGES: Serum miR-4482-3p, miR-146a-3p, circ_0008167 and circ_0003317 are dysregulated in NSCLC. Higher levels of serum circ_0008167 are associated with more malignant NSCLC. Multiple combinations of circRNAs and miRNAs show higher value to diagnose NSCLC.

NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK

We aim to investigate the roles and mechanisms of NR3C2 in colorectal cancer (CRC). The expression of NR3C2 in CRC tumours and paired paracancerous tissues of 71 CRC patients and five CRC cell lines was detected by western blotting, immunohistochemistry and real-time reverse-transcription PCR. Moreover, NR3C2 was overexpressed or knocked down in CRC cells by lentiviral vector transfection. The proliferation of cells was measured by MTT, colony formation assay and flow cytometry. Glucose metabolism was assessed by detecting lactate production, glucose consumption and ATP production. Western blotting and real-time reverse-transcription PCR were used to detect the expression of AMPK, LDHA and HK2. The expression of NR3C2 was significantly decreased in CRC tumours compared to paracancerous tissues, which was correlated with distant metastasis, poor prognosis and advanced stages of CRC patients. Overexpressing NR3C2 suppressed the proliferation and promoted the G2/M cell cycle arrest of CRC cells. Furthermore, NR3C2 inhibited glucose metabolism by decreasing the expression of HK2 and LDHA. The phosphorylation of AMPK was also downregulated in CRC cells overexpressing NR3C2. This study demonstrated that NR3C2 inhibited the proliferation of CRC by inhibiting glucose metabolism and phosphorylation of AMPK which may serve as a therapeutic target for CRC.

Updated racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous carcinoma in the United States.

This study was to determine the racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous cell carcinoma (HPSCC) in the US. The National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER) database was used to determine racial disparity in age adjusted incidence rate (AAIR) of HPSCC and its temporal trend during 2004-2019. Using the separate SEER 17 database, we further evaluated racial disparity in clinicopathological features, and in prognosis using Kaplan-Meier curves and Cox proportional hazard models. HPSCC accounted for 95.8% of all hypopharyngeal cancers and occurred much more frequently in males. Its incidence decreased in both male and females, in male non-Hispanic white (NHW), non-Hispanic black (NHB) and Hispanic as well as female NHW and NHB during the study period. NHB had the highest, whereas non-Hispanic Asian or Pacific Islanders (API) had comparable and the lowest incidence in both males and females. Among 6,172 HPSCC patients obtained from SEER 17 database, 80.6% were males and 83.9% were at the advanced stages III/IV. Five-year cancer specific and overall survival rates were 41.2% and 28.9%, respectively. NHB patients were more likely to be younger, unmarried, from the Southern region, larger sized tumor, and at the stage IV, but less likely to receive surgery. They also had higher proportions of dying from HPSCC and all causes. Multivariate analyses revealed that NHB with HPSCC at the locally advanced stage had both significantly worse cancer specific and overall survival compared with NHW, but not at early stage (I/II) or distant metastatic stage. Hispanic patients had significantly better prognosis than NHW at locally advanced and metastatic stages. NHW and API had comparable prognoses. HPSCC displays continuously decreased incidence and racial disparity. The majority of the disease is diagnosed at the advanced stage. NHB have the highest burden of HPSCC and a worse prognosis. More studies are needed to curtail racial disparity and improve early detection.

Gene Expression Analysis of Immune Regulatory Genes in Circulating Tumour Cells and Peripheral Blood Mononuclear Cells in Patients with Colorectal Carcinoma.

Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of p53, APC, KRAS, c-Myc, and immunotherapeutic target molecules PD-L1, CTLA-4, and CD47 in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages (p = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, p = 0.019), while being weakly correlated with tumour size (p = 0.051). Patients with lower numbers of CTCs had higher expression of KRAS. Higher KRAS expression in CTCs was negatively correlated with tumour perforation (p = 0.029), lymph node status (p = 0.037), distant metastasis (p = 0.046) and overall staging (p = 0.004). CTLA-4 was highly expressed in both CTCs and PBMCs. In addition, CTLA-4 expression was positively correlated with KRAS (r = 0.6878, p = 0.002) in the enriched CTC fraction. Dysregulation of KRAS in CTCs might evade the immune system by altering the expression of CTLA-4, providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.

Abstract P1-06-01: Associations of historic and contemporary “redlining” with breast cancer stage at diagnosis

Abstract Breast cancer is the most commonly diagnosed cancer among US women across all racial/ethnic groups. Stage at diagnosis is one of the major factors determining breast cancer prognosis. The 5-year relative survival for breast cancer ranges from 99% for localized stage at diagnosis, to 84% for regional stage, and to 27% for distant (metastatic) stage breast cancer. The proportion of women diagnosed with breast cancer at later stages (regional and distant) in the US are higher among women with lower socio-economic status and among non-Hispanic Black women. Historic mortgage security redlining, implemented by the Home Owners’ Loan Corporation (HOLC) in the 1930s across numerous US cities, continues to have a negative influence on breast cancer stage at diagnosis, largely due to continued social and economic isolation and poor living environments resulting in many adverse consequences, including lower education, limited job opportunities, no/limited health insurance coverage, and suboptimal access to care, including cancer screening services. Additionally, studies have reported that living in areas with greater contemporary mortgage lending bias towards the non-Hispanic Black population (measured as higher odds of mortgage denial) is associated with late-stage breast cancer diagnosis in several US metropolitan areas. In this study, we aim to examine the association between the historic HOLC-based “redlining” and contemporary mortgage lending bias and stage of breast cancer at diagnosis among women aged 18 years and older in New Jersey diagnosed with first primary invasive breast cancer in 2010-2015 (N= 32,939). The study population was derived from the New Jersey State Cancer Registry. Historic “redlining” data based on 1930s neighborhood boundaries and transformed to corresponding 2010 census tracts borders were obtained from Inter-university Consortium for Political and Social Research. Mortgage lending bias score for the study period was calculated at the census tract level following methodology developed by Beyers and colleagues. Associations between census tract-level historic “redlining”, contemporary mortgage lending bias and breast cancer stage at diagnosis were evaluated using multinomial logistic regression models after adjusting for age alone, and then for age, race/ethnicity, marital status, and health insurance status. The study included 21,038 local, 9,765 regional, and 2,136 distant stage breast cancer cases. After adjusting for age, race/ethnicity, marital status, and health insurance, women living in historically redlined census tracts were more likely to be diagnosed with regional (OR=1.23; 95% CI 1.03-1.48) and distant (OR=1.55; 95% CI 1.09-2.22) stage breast cancer compared to women living in other census tracts. Odds for regional (OR=1.14; 95% CI 1.06-1.23) and distant (OR=1.33; 95% CI 1.16-1.53) stage breast cancer were also significantly higher for women living in areas with highest mortgage lending bias score. Stratifying by age (&amp;lt; 65 and &amp;gt;=65 years) showed similar patterns (data not shown). Both historic “redlining” and contemporary mortgage lending bias were associated with being diagnosed with breast cancer at later stages, notably distant stage. Targeting the legacy of systematic racism and addressing any contemporary discriminatory policies may help reduce breast cancer disparities in the diagnosis stage and thus mortality. Association between the historic redlining and contemporary mortgage lending bias and stage of breast cancer at diagnosis among women aged ≥18 years in New Jersey, 2010-2015 Note: For contemporary mortgage lending bias, highest score is indicative of highest bias (highest proportion of mortgage denial) towards Black people. *Fully adjusted model includes covariates: age, race/ethnicity, marital status, health insurance status ^Areas designated ”Best” were individual housing markets with sufficient levels of financing and were preserved exclusively for White and wealthy population. Areas defined as “Hazardous” were those lacking financial resources and were designated for Black and poor population. Citation Format: Daniel Wiese, Antoinette M. Stroup, Ahmedin Jemal, Kevin A. Henry, Farhad Islami. Associations of historic and contemporary “redlining” with breast cancer stage at diagnosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-01.

CCNB2 as a potential biomarker of bladder cancer via the high throughput technology.

Bladder cancer and oral squamous cell carcinoma (OSCC) seriously affect people's health. However, the relationship between bladder cancer and OSCC remains unclear. Got GSE138206, GSE146483, GSE184616, and bladder cancer datasets GSE65635, GSE100926 from Gene Expression Omnibus database. Weighted gene co-expression network analysis was used to identify the significant module. Functional enrichment analysis was performed via the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes. Furthermore, the Gene Set Enrichment Analysis was also used to complete the enrichment analysis. Comparative Toxicogenomics Database found most relevant diseases to core genes. TargetScan is used to forecast analysis of microRNA and target genes. In Gene Ontology analysis, differentially expressed genes were mostly concentrated in cell differentiation, extrallular region, structural molecule activity, and actin binding. In Kyoto Encyclopedia of Genes and Genomes analysis, the differentially expressed genes were mainly enriched in PI3K-Akt signaling pathway, pathway in cancer, and extracellular matrix-receptor interaction. Seven hub genes (cyclin B2 [CCNB2], TK1, CDC20, PCNA, CKS1B, CDCA5, MCM4) were obtained. Hub genes (CCNB2, CDC20) are highly expressed in OSCC and bladder cancer samples. CCNB2 was one common oncogene of bladder cancer and OSCC.

MIR503HG Overexpression Inhibits the Malignant Behaviors of Osteosarcoma Cells by Sponging miR-103a-3p

Osteosarcoma (OS) is the most representative primary bone tumour in children and teenagers. This study explored the regulatory effects of long noncoding RNA MIR503HG (MIR503HG) on the biological functions of OS cells, and further investigated the potential mechanism of MIR503HG function exertion by analyzing the microRNA-103a-3p (miR-103a-3p) in OS cells and tissues. The expression of MIR503HG was examined using reverse transcription-quantitative PCR. OS cell proliferation was assessed by CCK-8 assay. Transwell assay was used to evaluate the migration and invasion of OS cells. The interaction between MIR503HG and miR-103a-3p was detected using the Dual-luciferase reporter assay. Forty-six paired OS tissues were collected, and the expression and correlation of MIR503HG and miR-103a-3p were evaluated. The expression of MIR503HG were significantly decreased in both OS cells and tissues. Over-expression of MIR503HG inhibited OS cell proliferation, migration and invasion. miR-103a-3p was directly targeted by MIR503HG in OS cells, and mediated the inhibitory effects of MIR503HG on OS cell malignant behaviors. miR-103a-3p expression was upregulated in OS tissues, which was negatively correlated with MIR503HG expression levels. The expression of MIR503HG was associated with OS patients' tumor size, differentiation, distant metastasis and clinical stage. Decreased MIR503HG in OS tissues and cell lines served as a tumor suppressor by inhibiting OS cell malignant behaviors through sponging miR-103a-3p. The findings of this study may provide evidence for the development of novel therapeutic targets of OS.

Clinical and Prognostic Significance of PD-L1, Beclin 1 and Fascin 1 Immunohistochemical Expression in Colorectal Carcinoma

Introduction: Colorectal Cancer (CRC) is a leading cause of death worldwide, and its incidence has been rising. It is important to identify novel markers that could predict the prognosis of the disease. Aim: To identify the impact of Programmed cell death-ligand 1 (PD-L1), Beclin 1, and Fascin 1 immunohistochemical expression on CRC behaviour and disease prognosis. Also, to assess the different surgical options (laparoscopic versus open) in the management of these patients. Materials and Methods: This cohort study included 72 cases of CRC, conducted in the Pathology, General Surgery, Internal Medicine, Clinical Oncology, and Medical Oncology Departments of the Faculty of Medicine, Zagazig University Hospitals, Egypt between June 2018 and June 2022. PD-L1, Beclin 1, and Fascin 1 expression were assessed immunohistochemically, and their prognostic significance were evaluated. Data were analysed using IBM Statistical Package for the Social Sciences (SPSS) 23.0 for Windows (SPSS Inc., Chicago, IL, USA) and NCSS 11 for Windows (NCSS LCC., Kaysville, UT, USA) in the Community Medicine Department, Faculty of Medicine, Zagazig University, Egypt. Results: A significant association was found between PDL1 expression and grading (p-value=0.02), lymphovascular invasion, distant metastasis (p-value=0.001), peritoneal spread (p-value=0.002), tumour budding (p-value=0.005), lymph node metastasis, and American Joint Committee on Cancer (AJCC) stage (p-value&lt;0.001). A significant association was also found between Beclin 1 expression and distant metastasis (p-value=0.001), lymphovascular invasion (p-value=0.004), lymphocytic infiltration (p-value=0.006), perineural invasion (p-value=0.01), peritoneal spread (p-value=0.002), and AJCC stage (p-value=0.007). A highly significant association between Fascin 1 expression and grading, lymphovascular invasion, tumour budding, lymph node metastasis, lymphocytic infiltration, perineural invasion, metastasis, peritoneal spread, and AJCC stage (p-value&lt;0.001) was detected. In patients with negative PD-L1 or high Fascin 1 expression, survival rates were lower. Beclin 1 expression was not associated with a favourable prognosis (p-value&gt;0.05). Conclusion: PD-L1, Beclin 1, and Fascin 1 expression are significantly elevated in CRC tissues and closely associated with adverse prognostic factors. PD-L1 and Fascin 1 expression have important prognostic value and may be of great help in identifying high-risk patients who will benefit the most from treatment.

Survival analysis of ovarian cancer patients with distant metastasis after chemotherapy: A SEER-based study.

This study investigated the overall survival (OS) of patients with distant metastasis of ovarian cancer after chemotherapy and surgery, and explored differences in the survival of these patients with single-site metastasis. We selected only patients with stage IV ovarian cancer who had undergone chemotherapy. Using GraphPad Prism 7 software and Kaplan-Meier survival analysis, we confirmed the factors that were meaningful for OS. Survival-related risk factors were compared using the Cox proportional hazards model. Patients with lung, bone, and brain metastasis experienced shorter survival than patients with liver metastasis who underwent chemotherapy. Among patients with distant metastasis who underwent chemotherapy and surgery, patients with brain metastasis experienced longer survival than patients with liver metastasis, while patients with bone and lung metastasis presented shorter survival than patients with liver metastasis. Finally, surgery prolonged the survival of patients with stage IV ovarian cancer with single-site metastasis, who were treated with chemotherapy. Chemotherapy combined with surgery significantly prolonged OS and cancer-specific survival (CSS) of patients with distant metastatic stage IV ovarian cancer. Lung metastasis resulted in a shorter survival than liver metastasis in patients treated with chemotherapy alone or in combination with surgery.

Identification of EGFR-Related LINC00460/mir-338-3p/MCM4 Regulatory Axis as Diagnostic and Prognostic Biomarker of Lung Adenocarcinoma Based on Comprehensive Bioinformatics Analysis and Experimental Validation.

Simple SummaryWhile the epidermal growth factor receptor (EGFR) is an important target for lung adenocarcinoma (LUAD) therapy, acquired resistance is still inevitable. A comprehensive bioinformatics analysis strongly suggested that the closely related LINC00460-mir-338-3p-MCM4 ceRNA network of EGFR plays an important role in the diagnosis and prognosis of LUAD. High expression of LINC00460 and MCM4 predicts shorter patient survival. Univariate and multivariate regression analyses demonstrated that higher expression of LINC00460 and MCM4 was significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation))—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes.Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, the regulation of the EGFR by competing endogenous RNAs (ceRNAs) has been extensively studied and significant progress has been made. Therefore, we aim to find new targets for the diagnosis and treatment of LUAD by analyzing the EGFR-related ceRNA network in LUAD and expect to address the problem of EGFR resistance. Methods: We identified differentially expressed lncRNAs, miRNAs and mRNAs closely associated with the EGFR by analyzing transcriptome data from LUAD samples. Comprehensive bioinformatics analysis strongly suggests that the LINC00460—mir-338-3p—MCM4 ceRNA network plays an important role in the diagnosis and prognosis of LUAD. The effects of different patterns of the LINC00460/MCM4 axis on the overall survival of patients with LUAD were analyzed by a polygene regulation model. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. The functional enrichment analysis and targeted drug prediction of the MCM4 gene were performed. Results: Survival analysis indicated that high expressions of LINC00460 and MCM4 predict a shorter survival period for patients. Univariate and multivariate regression analyses demonstrated that higher expressions of LINC00460 and MCM4 were significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation)—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients (p = 0.0093). RT-PCR and immunohistochemical experiments confirmed our analytical results. In addition, the functional enrichment analysis indicated that MCM4-related genes were mainly enriched in the cell cycle and cell division. A functional association network analysis showed that MCM4 was closely related to the EGFR. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes. Conclusions: In summary, the LINC00460/MCM4 axis can be used as a potential new perspective for targeting EGFR genes in precision medicine and is expected to serve as a diagnostic, prognostic and drug target for LUAD.

Evaluation of relationship between maximum SUV measured on 18F-FDG PET/CT with tumor pathological types, size, lymph node metastasis and distant metastasis in non-small cell lung cancer

BackgroundLung cancer is the most commonly diagnosed cancer, of which the non-small cell lung cancer (NSCLC) accounts for approximately 80% of the newly diagnosed lung cancer. The prognosis of lung tumors depends on early and accurate staging as well as the histopathological type of the tumor. It is suggested that NSCLC with different histopathological types and primary tumor sizes can elicit variable max.SUV values on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG) PET/CT with different lymph nodes and distant metastatic potential. In this study, we aim to evaluate the relationship between the maximum SUV measured on (18F-FDG) PET/CT with tumor pathological type, primary tumor size, lymph node metastasis, and distant metastasis in NSCLC.ResultsThis is a cross-sectional analysis of the (FDG-PET/CT) findings of 40 patients with NSCLC. Statistical analysis is used to determine correlation between max.SUV and tumor size, with each pathological type, nodal (N) staging and distant metastasis (M) staging. The primary lung tumors histopathological types were 25 (62.5%) adenocarcinomas, 12 (30%) squamous cell carcinomas and 3 (7.5%) large cell carcinomas. The max.SUV and tumor size of the squamous cell carcinoma group were significantly higher than max.SUV of adenocarcinoma and large cell cancer groups (P = 0.000009). A significant positive correlation was found between the primary tumor max.SUV and tumoral size. Neither lymph node nor distant metastases involvement was correlated with tumor max.SUV.ConclusionsThe tumor size and histologic subtype both strongly influence FDG uptake in lung cancer. Nonetheless, max.SUV cannot be regarded as a predictive of metastases or lymph node involvement.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis.

BACKGROUNDTwist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial.AIMTo investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.METHODSPublished literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated by I2 statistics.RESULTSEleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69, I2 = 68.6%), and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84 (95%CI: 1.12-3.02, I2 = 67.1%), suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients. In addition, overexpression of Twist was correlated with T stage (T3 + T4 vs T1 + T2, RR = 1.38, 95%CI: 1.14-1.67), lymph node metastasis (yes vs no, RR = 1.34, 95%CI: 1.11-1.60), distant metastasis (yes vs no, RR = 1.18, 95%CI: 1.02-1.35), tumor, node and metastasis (TNM) stage (III + IV vs I + II, RR = 1.35, 95%CI: 1.14-1.60), and clinical stage (III + IV vs I + II, RR = 1.58, 95%CI: 1.34-1.87). However, no correlation between Twist expression and age, gender, tumor location, differentiation, or venous invasion was observed.CONCLUSIONHigh expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.

The role of circular RNA hsa_circ_0001789 as a diagnostic biomarker in gastric carcinoma

Background Circular RNA (circRNA) is a kind of endogenous non-coding RNAs and has shown diagnostic values in various cancers. This study aimed to explore whether hsa_circ_0001789 could be a novel biomarker for gastric cancer (GC). Methods Quantitative reverse transcriptase PCR was used to detect the expression of hsa_circ_0001789 in 108 paired GC and paracancerous tissues as well as in 24 paired plasma specimens. Possible associations between hsa_circ_0001789 expression and clinicopathologic factors of GC patients were examined using one-way ANOVA. A receiver operating characteristic (ROC) curve was established to investigate the diagnostic value of hsa_circ_0001789 in GC. Results GC tissues and plasma samples showed down-regulated hsa_circ_0001789 levels than their counterparts, which were closely correlated with the malignant characteristics of GC. The area under the ROC curve (AUC) of hsa_circ_0001789 in GC tissues was 0.82, while the cut-off value was 9.5, indicating a favorable diagnostic value. Compared with the traditional tumor biomarkers, hsa_circ_0001789 had preferred AUCs that reached 0.786 for predicting the stage of invasion, 0.603 for predicting the stage of lymphatic metastasis, 0.722 for predicting the stage of distant metastasis, and 0.786 for predicting TNM stage. Conclusions Hsa_circ_0001789 may be a novel biomarker for the diagnosis of gastric carcinoma.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BackgroundCircular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients.MethodsA systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta‐analysis.ResultsUltimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68–2.34) and disease/progression/recurrence‐free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85–2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40–0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28–0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively.ConclusionCircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

TUMOR BUDDING IN ORAL TONGUE SQUAMOUS CELL CARCINOMA BETWEEN YOUNGER AND OLDER INDIVIDUALS: A MORPHOLOGICAL STUDY

<h3>Objectives</h3> To morphologically analyze tumor budding (TB) in cases of oral tongue squamous cell carcinoma (OTSCC) between younger (<45 years-old) and older (≥45 years-old) individuals, correlating them with clinical parameters. <h3>Study Design</h3> The sample consisted of 60 cases of OTSCC, divided in 2 groups (30 cases in younger individuals and 30 cases in older individuals). Clinical parameters (harmful habits, tumor size, lymph node metastasis, distant metastasis, clinical staging, management, outcome, and survival) were obtained from medical records. Morphologically, TB was classified using 3 scores: absence, presence of <15 focus, and ≥15 focus. Statistical analysis employed Fischer's exact test, with <i>P</i> < .05. <h3>Results</h3> There was a significant difference in harmful habits (<i>P</i> = .049), distant metastasis (<i>P</i> = .020), and clinical staging (<i>P</i> = .024) between younger and elderly individuals. TB was present in 63.3% of the sample (<i>n</i> = 38), predominantly with <15 focus, with no significant difference between age groups. There was no significant association of TB with any of the morphologic parameters. <h3>Conclusions</h3> It is suggested that OTSCC in older individuals is diagnosed in later clinical stages and with distant metastasis. TB is observed in OTSCC, independent of age group.

EGFR, HER2, and HER3 protein expression in paired primary tumor and lymph node metastasis of colorectal cancer

Due to the difficulty in sampling of metastatic tumors, patient selection is commonly based on results of primary tumor samples when metastatic samples are not available. However, due to tumor heterogeneity, metastatic tumors may be different from primary tumors in their phenotypes. The aim of this study was to investigate the expression of EGFR, HER2, and HER3 between primary and lymph node metastatic lesions of colorectal cancer. Paired primary tumors and lymph node metastases from 79 patients with colorectal cancer were retrospectively collected and analyzed for EGFR, HER2, and HER3 expression. High EGFR, HER2, and HER3 expression (2+ and 3+) was found in 64.2%, 66.0%, and 85.0% of primary tumors, and 56.8%, 46.0%, and 76.0% of lymph node metastases, respectively. Correlation rates between primary and metastatic lesions were 67.1%, 63.3%, and 74.7% for EGFR, HER2, and HER3, respectively. Stage IV tumors (with distant metastasis) had higher correlation rates of HER2 expression compared to stage III tumors (without distant metastasis) (P = 0.050). Moderate correlation rates in EGFR, HER2, and HER3 expression were observed between primary and metastatic lesions of colorectal cancer. Tumor stage or existence of distant metastasis could serve as potential predictive markers for the correlation of HER2 expression between primary tumors and lymph node metastases of colorectal cancer.

Clinical Data and Biocalculation Methods of GABRD Determine the Clinical Characteristics and Immune Relevance of Colorectal Cancer.

Background The aim of this study was to clarify the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) gene in pan-cancer and its correlation with patient prognosis, and to investigate the function and possible mechanism of GABRD in colorectal cancer (CRC). Methods The Cancer Genome Atlas (TCGA) data were used to analyze the expression differences of GABRD in pan-cancer, and the correlation between GABRD and clinical prognosis of various tumors was analyzed by Cox regression method. According to the expression level of GABRD, Gene Function Annotation (GO) and Kyoto Encyclopedia of Genomes (KEGG) functional enrichment analysis were performed on the differentially expressed genes. Expression of GABRD gene and 44 marker genes of three types of RNA modification (m1A (10), m5C (13), m6A (21)) genes in different tumors was observed. Pearson correlation of GABRD gene and marker genes of five immune pathways was measured. Results: TCGA data analysis showed that GABRD was significantly upregulated in various tumor tissues, especially COAD and READCOAD. Survival analysis showed that GABRD was a prognostic protective factor in CRC (p < 0.001). The results of survival nomogram showed that GABRD, age, and tumor (T) lymph node (N) distant metastasis (M) stage were independent prognostic factors, and the survival model C-index was 0.724 (0.644-1). Gene enrichment and functional analysis showed that GABRD may be related to protein digestion and absorption, ECM-receptor interaction, extracellular structure organization, extracellular matrix organization, pancreatic secretion, and antimicrobial humoral response. The expression of GABRD was positively correlated in m1A-, m5C-, and m6A-related genes. The GABRD gene was found in B cell, T cell CD4, T cell CD8, neutrophil, macrophage in TCGA-COAD (N = 282), and TCGA-COADREAD (N = 373). The infiltration level and DC was significantly positively correlated (p < 0.05). Also, the Pearson correlation coefficient is the largest. Conclusion The involvement of GABRD in the occurrence and development of CRC may be related to protein digestion and absorption, ECM-receptor interaction, extracellular structure organization, extracellular matrix organization, pancreatic secretion, and antimicrobial humoral response. GABRD can be used as a molecular marker for the prognosis of CRC.

Clinicopathological and Prognostic Value of USP22 Expression in Gastric Cancer: A Systematic Review and Meta-Analysis and Database Validation.

BackgroundIt has been reported that there is a correlation between the level of ubiquitin-specific protease 22 (USP22) and the clinicopathological parameters and prognosis of gastric cancer (GC) patients, but the conclusions are inconsistent. Hence, a meta-analysis must be conducted to clarify the relationship between USP22 expression and clinicopathological and prognostic value of GC patients to provide more accurate evidence.MethodsAccording to the predetermined selection criteria, systematic file retrieval was performed. The hazard ratio (HR) or odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the relationship between USP22 expression and clinicopathological and prognostic value of GC patients.ResultsIn a total of 802 patients, those with GC were finally included in 6 studies. The pooled results demonstrated that the expression of USP22 was significantly increased in GC tissues compared with control tissues (OR = 9.947, 95% CI, 6.074–16.291, P = 0.000), and USP22 expression was related to lymph node metastasis (OR = 2.415, 95% CI, 1.082, P = 0.031), distant metastasis (OR = 3.956, 95% CI, 1.365–11.464, P = 0.011) and TNM stage (OR = 2.973, 95% CI, 1.153–7.666, P = 0.024). Nevertheless, the expression of USP22 was not correlated with gender (OR = 1.202, 95% CI, 0.877–1.648, P = 0.253), age (OR = 1.090, 95% CI, 0.811–1.466, P = 0.568), tumor size (OR = 0.693,95% CI, 0.348–1.380, P = 0.297), tumor differentiation (OR = 1.830, 95%CI, 0.948–3.531, P = 0.072) and depth of invasion (OR = 2.320, 95% CI, 0.684–7.871, P = 0.177). Moreover, a high expression of USP22 predicted a poor overall survival (OS) in GC patients (HR = 2.012, 95% CI, 1.522–2.658, P = 0.000). The database of Kaplan–Meier plotter confirmed that a high expression of USP22 was correlated with poor prognostics in GC patients (HR = 1.41, 95% CI, 1.18–1.68, P < 0.01).ConclusionUSP22 overexpression in GC tissues is positively related to lymph node metastasis, distant metastasis and TNM stage and indicates a poor clinical outcome of GC patients, but it is not associated with age, gender, depth of invasion, tumor differentiation and tumor size of GC patients.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: 338361.