Advanced Tumor Node Metastasis Stage Research Articles

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 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.

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.

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.

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.

Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6.

Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo. Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2'-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.

LINC00958 may be a new prognostic biomarker in various cancers: A meta-analysis and bioinformatics analysis.

Background: There have been many studies on long non-coding RNAs (lncRNAs) as tumor markers. LINC00958 is a lncRNA that has been studied in a variety of tumor types. This meta-analysis aims to explore the relationship between LINC00958 and clinical prognosis and pathological characteristics in various cancers. Methods: We searched for related studies from PubMed, Web of Science, The Cochrane Library and Embase (up to October 2021). The association of LINC00958 expression with clinicopathological characteristics and prognosis was evaluated using the pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). Results: 16 studies (1,121 patients) were included in this meta-analysis, we found that overexpression of LINC00958 was associated with poor overall survival (OS) (HR = 1.84; 95% CI: 1.36-2.49; p < 0.001). We also found that LINC00958 overexpression was correlated with positive lymph node metastasis (LNM) (OR = 1.91; 95% CI: 1.39-2.63; p < 0.001), advanced degree of infiltration (OR = 1.64; 95% CI: 1.11-2.41; p = 0.013), advanced tumor-node-metastasis (TNM) stage (OR = 2.80; 95% CI: 1.48-5.33; p = 0.002). Other clinicopathological characteristics have no obvious correlation, such as age, sex, tumor size, distant metastasis, and differentiation grade (p > 0.05). Conclusion: In summary, the overexpression of LINC00958 is significantly correlated with poor OS, positive LNM, advanced degree of infiltration, and advanced TNM stage. LINC00958 might serve as a potential prognostic biomarker and therapeutic target for a variety of cancers. However, rigorous studies with large sample sizes are still needed for further research and demonstration.

The Challenges of Colorectal Cancer Surgery during the COVID-19 Pandemic in Romania: A Three-Year Retrospective Study.

The predictions on the influence of the SARS-CoV-2 pandemic on access to medical services in Romania predicted a 35% drop in oncological hospitalizations in 2020 compared to the previous decade, raising the hypothesis that patients with colorectal cancer can become indirect victims of the ongoing pandemic. Therefore, the aim of the current research was to observe how the COVID-19 pandemic influenced colorectal cancer surgery in Romania, to determine the level of addressability towards specialized care, to compare the cancer staging between the pandemic and pre-pandemic periods, and to observe the risk factors for disease progression. This retrospective study was spread over three years, respectively, from March 2019 to March 2022, and included a total of 198 patients with a history of colorectal cancer surgery. It was decided to perform a parallel comparison of 2019, 2020, and 2021 to observe any significant changes during the pandemic. Our clinic encountered a significant decrease in all interventions during the pandemic; although the number of CRC surgeries remained constant, the cases were more difficult, with significantly more patients presenting in emergency situations, from 31.3% in 2019 to 50.0% in 2020 and 57.1% in 2021. Thus, the number of elective surgeries decreased significantly. The proportion of TNM (tumor-node-metastasis) staging was, however, statistically significant between the pre-pandemic and pandemic period. In 2019, 13.3% of patients had stage IIa, compared with 28.8% in 2020 and 13.1% in 2021. Similarly, the proportion of very advanced colorectal cancer was higher during the pandemic period of 2020 and 2021 (12.0% in 2019 vs. 12.5% in 2020 and 25.0% in 2021), which was represented by a significantly higher proportion of patients with bowel perforation. Patients with an advanced TNM stage had a 6.28-fold increased risk of disease progression, followed by lymphovascular invasion (HR = 5.19). However, the COVID-19 pandemic, represented by admission years 2020 and 2021, did not pose a significant risk for disease progression and mortality. In-hospital mortality during the pandemic also did not change significantly. After the pandemic restrictions have been lifted, it would be advisable to conduct a widespread colorectal cancer screening campaign in order to identify any instances of the disease that went undetected during the SARS-CoV-2 pandemic.

Elevated serum neutrophil-lymphocyte ratio is associated with worse long-term survival in patients with HBV-related intrahepatic cholangiocarcinoma undergoing resection.

This study aimed to examine the influence of serum inflammatory marker levels on long-term outcomes after liver resection in patients with intrahepatic cholangiocarcinoma (ICC). Data from 1189 consecutive ICC patients who underwent liver resection were reviewed. The serum neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were measured before surgery. Overall survival (OS) and tumour recurrence were analysed using the Kaplan-Meier method and compared using the log-rank test. Independent risk factors for OS and tumour recurrence were analysed using the Cox hazard regression model. We identified elevated serum NLR (≥ 2.15) as an independent risk factor for both OS and tumour recurrence (hazard ratio [HR]: 1.327, 95% confidence interval [CI]: 1.105-1.593; HR: 1.274, 95% CI: 1.074-1.510) among the three inflammatory markers assessed. Elevated NLR was associated with higher carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels, larger tumour size, multiple tumours, lymph node metastasis, vascular invasion, and more advanced tumour node metastasis (TNM) stage (III/IV). Subgroup analysis showed that elevated NLR was an independent risk factor for OS and tumour recurrence in patients with hepatitis B virus (HBV) infection compared with patients without HBV infection (HR: 1.347, 95% CI: 1.073-1.690; HR: 1.386, 95% CI: 1.112-1.726). Elevated serum NLR was associated with worse prognosis among ICC patients who underwent liver resection, especially in patients with HBV infection.

Correlations of cofilin1 and phosphorylation at Ser3 site with sensitivity of elderly patients with non-small cell lung cancer to radiotherapy

Abstract Background: To explore the correlations of cofilin1 (CFL1) and phosphorylation level of locus serine residue at position 3 (Ser3) with the sensitivity of elderly patients with non-small cell lung cancer (NSCLC) to radiotherapy. Methods: A total of 102 eligible patients treated from June 2013 to April 2015 were selected. The cases of complete remission and partial remission were included into radiotherapy-sensitive group (n=55), while those of stable disease and progressive disease were enrolled into radiotherapy-resistant group (n=47). Before treatment, tissues were collected to detect the expressions of CFL1 and CFL1 (phospho S3) by immunohistochemistry. The survival time and rate were recorded during follow-up. Results: Compared with the radiotherapy-sensitive group, the radiotherapy-resistant group had advanced tumor-node-metastasis (TNM) stage and higher lymph node metastasis rate (P=0.000, 0.000). Compared with the tissues with negative CFL1 expression, the tissues with positive CFL1 expression had advanced TNM stage and higher lymph node metastasis rate (P=0.013, 0.000). The positive expression rate of CFL1 in the radiotherapy-resistant group was higher than that of the radiotherapy-sensitive group, whereas the positive expression rate of CFL1 (phospho S3) in the former was lower (P=0.000, 0.000). Lymph node metastasis, high CFL1 expression, and low CFL1 (phospho S3) expression were independent predictors for resistance to radiotherapy (P=0.001, 0.006, 0.003). In the radiotherapy-sensitive group, the patients with negative CFL1 expression and positive CFL1 (phospho S3) expression had long progression-free survival and high 5-year survival rate (P=0.000, 0.000). Conclusion: The sensitivity to radiotherapy of elderly NSCLC patients is correlated negatively with CFL1 and positively with phosphorylation at locus Ser3. CFL1 and phosphorylation at locus Ser3 are independent predictors for sensitivity to radiotherapy.

Cuproptosis-related gene FDX1 expression correlates with the prognosis and tumor immune microenvironment in clear cell renal cell carcinoma.

BackgroundCuproptosis, a newly discovered form of cell death, is regulated by protein lipoylation and is related to mitochondrial metabolism. However, further research is needed to determine how the cuproptosis-related gene ferredoxin 1 (FDX1) affects the tumor immune response and its prognostic significance in clear cell renal cell carcinoma (ccRCC).MethodsThe Cancer Genome Atlas was used to screen for FDX1 gene expression in ccRCC and healthy tissue samples. The results were validated using the Gene Expression Omnibus and the Human Protein Atlas. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship between FDX1 gene expression, clinicopathological parameters, and overall survival (OS). The protein network containing FDX1 gene interaction was constructed using the online Search Tool for the Retrieval of Interacting Genes/Proteins. The relationship between FDX1 gene expression and immune cell infiltration in ccRCC was examined using Gene Ontology, gene set enrichment analysis (GSEA), and a single-sample GSEA. Using the Gene Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource databases, we investigated the relationship between FDX1 gene expression, the degree of immune cell infiltration, and the corresponding gene marker sets.ResultsccRCC samples had significantly (p < 0.05) lower FDX1 gene expression levels than normal tissue samples. Lower FDX1 gene expression levels were strongly associated with higher cancer grades and more advanced tumor–node–metastasis stages. The findings of multivariate and univariate analyses illustrated that the OS in ccRCC patients with low FDX1 expression is shorter than in patients with high FDX1 expression (p < 0.05). Ferredoxin reductase and CYP11A1 are key proteins interacting with the FDX1 gene, and ccRCC with an FDX1 enzyme defect was associated with a low number of invading immune cells and their corresponding marker.ConclusionIn ccRCC, decreased FDX1 expression was linked to disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration.