Advanced Tumor Node Metastasis Stage Research Articles

WNT5B promotes the malignant phenotype of non-small cell lung cancer via the FZD3–DVL3–RAC1–PCP–JNK pathway

The WNT5B ligand regulates the non-canonical wingless-related integration site (WNT)–planar cell polarity (PCP) pathway. However, the detailed mechanism underlying the activity of WNT5B in the WNT–PCP pathway in non-small cell lung cancer (NSCLC) is unclear. In this study, we assessed the clinicopathological significance of WNT5B expression in NSCLC specimens. WNT5B-overexpression and -knockdown NSCLC cell lines were generated in vivo and in vitro, respectively. WNT5B overexpression in NSCLC specimens correlates with advanced tumor node metastasis (TNM) stage, lymph node metastasis, and poor prognosis in patients with NSCLC. Additionally, WNT5B promotes the malignant phenotype of NSCLC cells in vivo and in vitro. Interactions were identified among WNT5B, frizzled3 (FZD3), and disheveled3 (DVL3) in NSCLC cells, leading to the activation of WNT–PCP signaling. The FZD3 receptor initiates DVL3 recruitment to the membrane for phosphorylation in a WNT5B ligand-dependent manner and activates c-Jun N-terminal kinase (JNK) signaling via the small GTPase RAC1. Furthermore, the deletion of the DEP domain of DVL3 abrogated these effects. Overall, we demonstrated a novel signal transduction pathway in which WNT5B recruits DVL3 to the membrane via its DEP domain through interaction with FZD3 to promote RAC1–PCP–JNK signaling, providing a potential target for clinical intervention in NSCLC treatment.

Risk factors for distant metastasis and prognosis of the penile cancer with distant metastasis.

Penile cancer (PC) is a rare malignant tumor, whose distant metastasis (DM) is associated with the poorest outcomes. The risk factors associated with DM and prognosis of the PC with DM remain elusive. This study was aimed at investigating risk factors associated with DM and constructing prediction models of PC with DM. This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database over a period of 2000-2020, including clinical characteristics such as age, marital status, tumor size, Tumor Node Metastasis (TNM) staging, and treatment information. Utilizing univariate and multivariate logistic regression, alongside cox regression analysis, we identified independent risk factors for DM and prognosis in the total cases and the cases with DM. Nomograms were developed for predicting DM and prognosis in PC patients. Enrolling 1,488 cases, our study identified tumor size and N stage as independent predictors of DM. The predictive nomogram for DM achieved an area under the curve (AUC) of 0.904. Notably, the 1-, 3-, and 5-year cumulative survival rates for PC with DM were 35%, 17%, and 13%, respectively, with larger tumor size associated with prognosis of PC cases with DM. This study verified a correlation between advanced age and TNM stage, as well as chemotherapy with the poor PC prognosis. The nomogram yielded 0.72, 0.69 and 0.69, in predicting 1-, 3-, and 5-year overall survivals (OS), while 0.73, 0.70 and 0.69 in predicting 1-, 3-, 5-year cancer specific survivals (CSS), respectively. This study investigated risk factors of PC with DM. Also, nomograms for predicting DM, OS and CSS of PC patients were developed.

Telomere-related gene risk model for prognosis prediction in colorectal cancer.

Colorectal cancer (CRC) is the third-most prevalent cancer globally. The biological significance of telomeres in CRC carcinogenesis and progression is underscored by accumulating data. Nevertheless, not much is known about how telomere-related genes (TRGs) affect CRC prognosis. Therefore, the aim of this study was to investigate the role of TRGs in CRC prognosis. We retrospectively obtained the expression profiles and clinical data of CRC patients from public databases. Utilizing least absolute shrinkage and selection operator (LASSO) regression analysis, we created a telomere-related risk model to predict survival outcomes, identifying ten telomere-related differentially expressed genes (TRDEGs). Based on TRDEGs, we stratified patients from The Cancer Genome Atlas (TCGA) into low- and high-risk subsets. Subsequently, we conducted comprehensive analyses, including survival assessment, immune cell infiltration, drug sensitivity, and prediction of molecular interactions using Kaplan-Meier curves, ESTIMATE, CIBERSORT, OncoPredict, and other approaches. The model showed exceptional predictive accuracy for survival. Significant differences in survival were observed between the two groups of participants grouped according to the model (P<0.001), and this difference was further confirmed in the external validation set (GSE39582) (P=0.004). Additionally, compared to the low-risk group, the high-risk group exhibited significantly advanced tumor node metastasis (TNM) stages, lower proportions of activated CD4+ T cells, effector memory CD4+ T cells, and memory B cells, but increased ratios of M2 macrophages and regulatory T cells (Tregs), elevated tumor immune dysfunction and exclusion (TIDE) scores, and diminished sensitivity to dabrafenib, lapatinib, camptothecin, docetaxel, and telomerase inhibitor IX, reflecting the signature's capacity to distinguish clinical pathological characteristics, immune environment, and drug efficacy. Finally, we validated the expression of the ten TRDEGs (ACACB, TPX2, SRPX, PPARGC1A, CD36, MMP3, NAT2, MMP10, HIGD1A, and MMP1) through quantitative real-time polymerase chain reaction (qRT-PCR) and found that compared to normal cells, the expression levels of ACACB, HIGD1A, NAT2, PPARGC1A, and TPX2 in CRC cells were elevated, whereas those of CD36, SRPX, MMP1, MMP3, and MMP10 were reduced. Overall, we constructed a telomere-related biomarker capable of predicting prognosis and treatment response in CRC individuals, offering potential guidance for drug therapy selection and prognosis prediction.

High-expression of V-domain Imuunoglobulin Suppressor of T-cell Activation (VISTA) Is Correlated with Advanced Pathological Features in Patients with Pancreatic Ductal Adenocarcinoma

V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry. Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation. Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival. In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes.

Value of the HOTAIR expression assay in predicting therapy target in hepatocellular carcinoma: A meta-analysis and bioinformatics analysis.

Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma. Eligible literature was systematically retrieved from PubMed, Embase, and Web of Science databases. The pooled hazard ratios with 95% confidence intervals were used to evaluate to the effect. Raw data on HOTAIR expression were obtained from The Cancer Genome Atlas data portals. All bioinformatics analyses were performed using R software (version 4.3.1). We identified eight studies in this meta-analysis with a total of 399 patients. High-level HOTAIR expression was found to be significantly related to advanced tumor node metastasis stage, distant metastasis, poor tumor differentiation, and patients with hepatitis. Correspondingly, HOTAIR was also associated with poor overall survival and relapse-free survival. Subsequently, in bioanalysis, HOTAIR expression was higher in hepatocellular carcinoma as well as poor overall survival. High HOTAIR expression was strongly correlated with tumor node metastasis stage. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes related to HOTAIR may be involved in the cancer-associated signaling pathway. HOTAIR may be a potential biomarker for HCC prediction and is expected to become a new choice for clinical HCC prediction..

Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway.

Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression. GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments. Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression. High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

The correlation study between TOP2A gene expression in circulating tumor cells and chemotherapeutic drug resistance of patients with breast cancer

BackgroundPatients with breast cancer (BC) at advanced stages have poor outcomes because of high rate of recurrence and metastasis. Biomarkers for predicting prognosis remain to be explored. This study aimed to evaluate the relationships between circulating tumor cells (CTCs) and outcomes of BC patients.Patients and methodsA total of 50 female were enrolled in this study. Their diagnoses were determined by clinical characteristics, image data, and clinical pathology. CTC subtypes and TOP2A gene expression on CTCs were detected by CanPatrol™ technology and triple color in situ RNA hybridization (RNA-ISH), which divided into epithelial CTCs (eCTCs), mesenchymal CTCs (MCTCs), and hybrid CTCs (HCTCs) based on their surface markers. Hormone receptor, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, was measured by immunohistochemistry (IHC) method before treatment. The risk factors for predicting recurrence and metastasis were calculated by COX risk regression model. The progression-free survival (PFS) of patients was determined using Kaplan–Meier survival curve.ResultsThe patients with a large tumor size (≥ 3 cm) and advanced tumor node metastasis (TNM) stages had high total CTCs (TCTCs) (P < 0.05). These patients also had high TOP2A expression level. COX risk regression analysis indicated that TOP2A expression levels in TCTCs, ER + , HER-2 + , and TNM stages were critical risk factors for recurrence and metastasis of patients (P < 0.05). The PFS of patients with ≥ 5 TCTCs, ≥ 3 HCTCs, and positive TOP2A expression in ≥ 3 TCTCs was significantly longer than that in patient with < 5 TCTCs, < 3 HCTCs, and TOP2A expression in < 3 TCTCs (P < 0.05). In contrast, the PFS of patients with positive hormone receptors (ER + , PR + , HER-2 +) also was dramatically lived longer than that in patients with negative hormone receptor expression.ConclusionsHigh TCTC, HCTCs, and positive TOP2A gene expression on CTCs were critical biomarkers for predicting outcomes of BC patients. Positive hormone receptor expression in BC patients has significant favor PFS.

IL-17 expression and prognosis of laryngeal squamous cell carcinoma.

Objective: To investigate the roles of proinflammatory cytokine IL-17 in the prognosis of laryngeal squamous cell carcinoma (LSCC). Methods: In all, 67 LSCC patients were enrolled to evaluate the expression of IL-17, IL-23, CD8, CD31, and vascular endothelial growth factor by immunohistochemical staining. Cumulative survival time was determined by the Kaplan-Meier approach, and prognostic variables for overall survival (OS) were identified by Cox proportional-hazards models. Results: The expression of IL-17 and IL-23 was remarkably higher in LSCC tissue than in adjacent normal (AN) tissue (P < .001). The Kaplan-Meier analysis indicated that patients with cervical lymph node metastasis (CLNM), advanced tumor node metastasis (TNM) stage, poor-differentiated grade, high microvessel density (MVD) in LSCC tissues, and high IL-17 expression in AN tissues had poorer OS (all P < .05). Cox regression analysis revealed that CLNM (HR = 7.246; 95% CI: 2.598-20.208; P < .001), high MVD in tumor tissues (HR = 4.233; 95% CI: 1.482-12.092; P = .007), and low CD8 expression in AN tissues (HR = 3.996; 95% CI: 1.442-11.074; P = .008) were significantly associated with poorer OS in LSCC, while IL-17 expression in AN tissue was not. Conclusion: High IL-17 expression in AN tissues could indicate poor prognosis and may be a prognostic marker for LSCC. Low CD8 expression in AN tissues may represent poor frontline antitumor immunity and be associated with poor prognosis.

Long-term outcomes of intensity-modulated radiotherapy in limited-stage small-cell lung cancer classified according to AJCC 8th tumor node metastasis staging system.

The objective of this study was to assess treatment outcomes of intensity-modulated radiotherapy with concomitant chemotherapy and to identify prognostic factors on survival in patients with limited-stage small-cell lung cancer. A retrospective analysis was conducted on a cohort of seventy-two patients who received curative treatment between December 2011 and January 2023. Several clinical and biochemical parameters were examined as potential prognostic factors. The median age was 63 years, and 79% of them were males. Concomitant chemotherapy was administered in 83% of patients. Prophylactic cranial irradiation was applied in 61% of the cohort. Two and five-year overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS) rates were 50% and 25%, 38% and 24%, and 44% and 25%, respectively. Univariate analysis revealed that older age, comorbid lung disease, advanced tumor-node-metastasis (TNM) stage, radiotherapy (RT) alone, and the absence of prophylactic cranial irradiation (PCI) were adverse factors affecting OS. The advanced TNM stage emerged as a significant prognostic factor for LRFS and DFS, with a notable trend toward affecting OS. The TNM staging system is of significance in cases classified as limited-stage small-cell lung cancer due to its prognostic implications. Our results suggest that patients with more advanced TNM stage exhibit less favorable treatment outcomes, which may require individual tailoring of new systemic therapies.

Preoperative metabolic parameters of 18F-FDG PET/CT are associated with TNM stage and prognosis of colorectal cancer patients.

Colorectal cancer (CRC) is the third most frequent cause of cancer-related death, while tumor/node/metastasis (TNM) stage of American Joint Committee on Cancer is the guideline of making treatment strategy and predicting survival. The aim of this study is to investigate the association of preoperative 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), TNM stage, and prognosis of patients with CRC. From September 2016 to August 2022, a total of 132 patients were retrospectively and consecutively enrolled in this cross-sectional study, who were diagnosed as CRC by histopathology and received preoperative 18F-FDG PET/CT. Firstly, the correlation between the metabolic parameters and clinicopathological features of the primary tumors was investigated. Secondly, univariate and multivariate logistic regression analyses were used to estimate the odds ratio of the association between the clinical and metabolic parameters and the advanced TNM stage (stage III-IV). Thirdly, progression-free survival (PFS) was analyzed using Kaplan-Meier curves and Log-rank test. The results revealed that the metabolic tumor volume (MTV) >6.6 cm3 and serum carcinoembryonic antigen (CEA) >5.84 ng/mL were independently associated with advanced TNM stage (P=0.0009, 0.0011, respectively). Larger tumor size, higher tumor-to-liver standardized uptake value ratio, MTV, and total lesion glycolysis (TLG) were significantly correlated with advanced pT stage (stage 4), and higher TLG and MTV were significantly correlated with advanced pN stage (stage 1-2) (P<0.05), while no metabolic parameters were significantly correlated with metastasis status (P>0.05). Higher serum CEA and carbohydrate antigen 19-9 levels were significantly correlated with advanced pT, pN stage, and metastasis status (P<0.05). Patients were followed up for at least 1 year. The MTV >6.6 cm3 was significantly associated with worse PFS (P=0.032). 18F-FDG PET-CT can serve as a noninvasive tool for preoperatively staging CRC. The MTV >6.6 cm3 might be associated with advanced TNM stage and worse PFS.

Expression of RSK4 protein in non-small cell lung cancer tissues, adjacent tissues and its correlation with clinicopathological features.

To evaluate the expression of Ribosomal S6 kinase 4 (RSK4) protein in non-small cell lung cancer (NSCLC) tissues and adjacent non-tumor tissues, and to elucidate its correlation with clinicopathological features of NSCLC. We analyzed 100 NSCLC patients treated at the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2020 to June 2022. Patient demographics and clinical data, including gender, age, history of diabetes, tumor location, degree of tumor differentiation, lymph node metastasis, and clinical stage, were collected. RSK4 protein expression was assessed in tissue samples via immunohistochemical staining. RSK4 protein was positively expressed in 35.00% of cancerous tissues, significantly lower than the 69.00% observed in adjacent non-tumor tissues (P < 0.05). Patients with lower tumor differentiation, advanced Tumor Node Metastasis (TNM) stages, and lymph node metastases showed significantly reduced RSK4 expression compared to those with higher differentiation, earlier TNM stages, and no lymph node metastases (all P < 0.05). Cox regression analysis indicated that TNM stage, low differentiation, and lymph node metastases significantly influenced RSK4 expression (all P < 0.05). Survival analysis revealed a higher positive prognosis survival rate of 74.29% (26/35) among patients with positive RSK4 expression, versus 53.85% (35/65) in those with negative expression (P < 0.05). Spearman correlation analysis demonstrated a significant positive correlation of RSK4 expression with TNM stage, lymph node metastasis, and patient prognosis (all P < 0.05). Positive RSK4 expression in NSCLC tissues is significantly correlated with advanced cancer stage, poor differentiation, and presence of lymph node metastasis, suggesting a potential tumor suppressor role for RSK4 in NSCLC. This association underscores its prognostic relevance in NSCLC patients.

Expression of PTP4A1 in circulating tumor cells and its efficacy evaluation in patients with early- and intermediate-stage esophageal cancer.

The objective of this study is to investigate the expression of protein tyrosine phosphatase type I (PTP4A1) in circulating tumor cells (CTCs) in patients with early- and intermediate-stage esophageal cancer and its clinical value in evaluating patient prognosis. Tissue and peripheral blood samples were collected from patients with esophageal cancer, as well as their clinical data. Follow-up was performed on all patients. PTP4A1 expression in the CTCs of patients were analyzed by regression analysis, and its correlation with the clinical characteristics of esophageal cancer was discussed. The numbers of mixed tumor cells and T-CTCs were significantly correlated with lymph node metastasis. Advanced tumor-node metastasis (TNM) stage (odds ratio = 12.063) and lymph node metastasis (odds ratio = 13.541) were influencing factors of PTP4A1+MCTC expression disorders in patients with esophageal cancer. The receiver operating characteristic curve showed that TNM stage and lymph node metastasis had a high predictive efficiency for PTP4A1+MCTCs, with an area under the ROC curve of 0.725. PTP4A1+mixed tumor cells had strong predictive value for the efficacy of neoadjuvant therapy, with a sensitivity of 94.7% and a specificity of 63.6%. Advanced TNM stage and lymph node metastasis are influencing factors for increased CTCs and poor expression of PTP4A1 in patients with esophageal cancer.

Biological functions of miRNA-203b-3p/ZNF324 in laryngeal carcinoma.

The present study aimed to elucidate the role of MicroRNA-203b-3p (miRNA-203b-3p) in protecting the deterioration of laryngeal carcinoma through targeting ZNF324. Relative levels of miRNA-203b-3p and ZNF324 in laryngeal carcinoma tissues with different tumor node metastasis (TNM) staging and pathological grades were detected. Regulatory effects of miRNA-203b-3p on clonality, viability and 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio in M2E and TU212 cells were assessed. The binding relationship between miRNA-203b-3p and ZNF324 was evaluated by dual-luciferase reporter gene assay. The involvement of ZNF324 in cell phenotype changes of laryngeal carcinoma regulated by miRNA-203b-3p was explored by rescue experiments. MiRNA-203b-3p was downregulated in laryngeal carcinoma, especially in those with advanced TNM staging or pathological grade. Overexpression of miRNA-203b-3p reduced clonality, viability and EdU-positive ratio in M2E and TU212 cells. In addition, ZNF324 was upregulated in laryngeal carcinoma, which was negatively regulated by miRNA-203b-3p. ZNF324 was verified to be the target binding miRNA-203b-3p. Notably, overexpression of ZNF324 could partially reverse the inhibitory effects of miRNA-203b-3p on laryngeal carcinoma proliferation. MiRNA-203b-3p is downregulated in laryngeal carcinoma, which blocks laryngeal carcinoma cells to proliferate through targeting ZNF324 and thus alleviates cancer progression.

Current insights into the oncogenic roles of lncRNA LINC00355.

Long noncoding RNAs (lncRNAs) are a class of nonprotein-coding transcripts that are longer than 200 nucleotides. LINC00355 is a lncRNA located on chromosome 13q21.31 and is consistently upregulated in various cancers. It regulates the expression of downstream genes at both transcriptional and posttranscriptional levels, including eight microRNAs (miR-15a-5p, miR-34b-5p, miR-424-5p, miR-1225, miR-217-5p, miR-6777-3p, miR-195, and miR-466) and three protein-coding genes (ITGA2, RAD18, and UBE3C). LINC00355 plays a role in regulating various biological processes such as cell cycle progression, proliferation, apoptosis, epithelial-mesenchymal transition, invasion, and metastasis of cancer cells. It is involved in the regulation of the Wnt/β-catenin signaling pathway and p53 signaling pathway. Upregulation of LINC00355 has been identified as a high-risk factor in cancer patients and its increased expression is associated with poorer overall survival, recurrence-free survival, and disease-free survival. LINC00355 upregulation has been linked to several unfavorable clinical characteristics, including advanced tumor node metastasis and World Health Organization stages, reduced Karnofsky Performance Scale scores, increased tumor size, greater depth of invasion, and more extensive lymph node metastasis. LINC00355 induces chemotherapy resistance in cancer cells by regulating five downstream genes, namely HMGA2, ABCB1, ITGA2, WNT10B, and CCNE1 genes. In summary, LINC00355 is a potential oncogene with great potential as a diagnostic marker and therapeutic target for cancer.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75years in Korea. The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1year. Clinical data were retrospectively collected from electronic medical records. Primary treatment for prostate cancer in patients aged ≥75years included androgen deprivation therapy (ADT) (n=614), radical prostatectomy (RP) (n=114), and radiation therapy (n=62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n=571), and leuprolide+bicalutamide (n=330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. In patients with prostate cancer aged ≥75years, the most common treatment option was MAB, and the leuprolide+bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Assessment of the prognostic and clinicopathological significance of HOXA-AS2 in human cancers: a systematic review and meta-analysis.

Numerous studies have reported that abnormally HOXA cluster antisense RNA 2 (HOXA-AS2) expression plays a critical role in various cancers. Thus, we performed this meta-analysis to comprehensively evaluate the prognostic value of HOXA-AS2 in human cancers. Databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang Data, were searched to retrieve articles on HOXA-AS2 and the prognosis of cancer patients, which were then screened. The association between HOXA-AS2 and overall survival (OS) and the clinicopathological characteristics of patients with cancers were assessed using hazard ratios (HRs) and odds ratios (ORs) combined with 95% confidence intervals (CIs). A subgroup analysis and the Begg test were used to assess the risk of bias of the included studies. Data from The Cancer Genome Atlas (TCGA) were analyzed to verify the results, and the potential regulation mechanism of HOXA-AS2 in cancers was revealed by an immune analysis. A total of 17 articles, comprising 1,176 patients, were included in this meta-analysis. The results showed that high HOXA-AS2 expression was associated with worse OS, advanced tumor node metastasis (TNM) stage, larger tumor size, lymph node metastasis, and distant metastasis in cancer patients but was not related to age, sex, or poor histological grade. The results of the analysis of TCGA data further supported our findings. Additionally, the immune analysis revealed that the expression of HOXA-AS2 was associated with immune cell infiltration and various immune checkpoints. In summary, our results suggest that the high expression of HOXA-AS2 is associated with poor prognosis and the clinicopathological characteristics of cancer patients; thus, it could serve as a prognosis biomarker and therapeutic target for various cancers. However, the small sample size of this study and the inclusion of participants of a single race might have affected the generalizability of our findings. Thus, large-sample, multicenter studies need to be conducted to further evaluate the prognostic role of HOXA-AS2.

Preoperative monocyte to high-density lipoprotein ratio as a predictor of survival outcome of gastric cancer patients after radical resection.

Aim: This study aimed to verify the prognostic value of monocyte to high-density lipoprotein ratio (MHR) in gastric cancer patients after radical resection. Methods: The Cox proportional hazards model was used to determine the risk variables for survival. Results: Older age (>60years) (hazard ratio [HR]: 1.832; 95% CI:1.167-2.725; p =0.009), advanced tumor node metastasis stage (p <0.05), lymphatic invasion (HR: 1.639; 95% CI: 1.114-3.032; p <0.05), vascular invasion (HR: 2.002; 95% CI: 1.246-5.453; p =0.028) and high MHR (HR: 1.154; 95% CI: 1.062-2.315; p =0.021) were independent poor prognostic factors for gastric cancer patients after radical resection. Conclusion: Older age, advanced tumor node metastasis stage, lymphatic invasion, vascular invasion and high MHR were independent poor prognostic factors for gastric cancer patients after radical resection.

Evidence from a meta-analysis for the prognostic and clinicopathological importance of DKC1 in malignancies.

Aim: We conducted a meta-analysis to evaluate the prognostic and clinicopathological relevance of DKC1 in various cancers. Methods: We searched Web of Science, Embase, PubMed, Wanfang and CNKI. Stata SE15.1 was used to calculate the hazard ratio and relative risk with 95% CIs to assess the possible correlations between DKC1 expression levels and overall and disease-free survival, as well as with clinicopathological parameters. Results: We included nine studies, with a total of 2574 patients. There was a meaningful link between elevated DKC1 and poorer disease-free (p<0.001) and overall survival (p<0.001). Also, it was linked to advanced tumor node metastasis stage (p=0.005). Conclusion: High DKC1 expression was predictive of worse prognosis and poorer clinicopathological parameters.

LncRNA CASC19 promotes gastric cancer progression through preventing CREB1 protein ubiquitin/proteasome-dependent degradation.

Cancer susceptibility candidate 19 (CASC19) is a novel long non-coding RNA (lncRNA) that has been reported to implicate in the development and therapeutic resistance of various cancers. However, the biological functions and the underlying mechanisms of CASC19 in gastric cancer (GC) remain unclear. In this study, GC-related lncRNAs were screened by lnCAR-database analysis. Based on Gene Expression Profiling Interactive Analysis (GEPIA) database, GC survival analysis associated with CASC19 was carried out. Quantitative real-time PCR (qRT-PCR) and chromogenic in situ hybridization were adopted to determine the expression level of CASC19. 5-ethynyl-2'-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and cell cycle assay were used to measure the proliferation capabilities of GC cells. Wound healing assay, transwell migration and invasion assay were performed to detect the metastatic ability of GC cells. Furthermore, subcellular fractionation assay, mass spectrometry, RNA pull-down, RNA immunoprecipitation, western blot and protein stability assay were conducted to investigate the mechanism of CASC19 in GC. Here, we report that CASC19 exerts an oncogenic effect on GC. CASC19 was found to be elevated in GC and overexpression of CASC19 was associated with advanced TNM (tumor node metastasis) stage and poor prognosis. Functionally, CASC19 knockdown inhibited GC cells proliferation, migration and invasion, and induced cell cycle arrest. Mechanistically, CASC19 interacted with cAMP response element-binding protein 1 (CREB1) and enhanced its stability by preventing its ubiquitin/proteasome-dependent degradation. In conclusion, these findings suggest that CASC19 may act as a cancer accelerator in GC by regulating CREB1 stability and highlight CASC19 as a potential biomarker and a valuable therapeutic target for advanced GC.

Small breast epithelial mucin as a useful prognostic marker for breast cancer patients.

This study aimed to evaluate the clinical utility of small breast epithelial mucin (SBEM) as a prognostic biomarker in an independent patient cohort. The paraffin-embedded tissues and clinicopathological data of 105 patients with breast cancer were collected, and the expression of SBEM in breast cancer samples was detected by immunohistochemical staining. The correlations between clinicopathological variables and the expression of SBEM were analyzed, and its significance as a prognostic indicator for breast cancer patients was determined. Immunohistochemical staining revealed that SBEM was expressed mostly in the cytomembrane and cytoplasm, with markedly increased SBEM expression (≥4 points on staining intensity) observed in 34 of 105 breast cancer tissues (32.4%). Elevated expression of SBEM was found to be significantly associated with larger tumor size (P = 0.002), more frequent lymph node metastasis (P = 0.029), advanced tumor node metastasis stage (P = 0.005), reduced expression of the progesterone receptor (PR) (P = 0.002), and a higher Ki-67 index (P = 0.006). Survival analysis indicated that patients with elevated SBEM expression had worse overall survival (OS) (5-year OS rate: 50.5 vs 93.9% for high and low SBEM expression, respectively, P < 0.001) and disease-free survival (DFS) (5-year DFS rate: 52.8 vs 81.7% for high and low SBEM expression, respectively, P = 0.001) rates than those with low expression of SBEM. Univariate and multivariate Cox analyses demonstrated that elevated expression of SBEM (hazard ratio [HR] = 1.994, 95% confidence interval [CI]: 1.008-3.945, P = 0.047), tumor size (HR = 2.318, 95% CI: 1.071-5.017, P = 0.033), and PR status (HR = 0.195, 95% CI: 0.055-0.694, P = 0.012) were independent predictors of OS in breast cancer patients. Elevated expression of SBEM was associated with both aggressive tumor characteristics and poor survival, indicating its potential as a useful prognostic biomarker for breast cancer patients.