Background Neuroblastoma (NB) development is significantly impacted by telomere maintenance where telomerase activation acts as the triggering factor. The study demonstrated the practical use of telomerase activation-related genes in the diagnosis and prognosis of NB. Methods Weighted Gene Co-expression Network Analysis (WGCNA) and differential analysis were used to screen for prognostic-related genes in NB. Telomerase activation-related genes (TARG) were identified using Genecard and then intersected with the prognostic-related genes to obtain telomerase activation-related NB prognostic genes. The key prognosis genes were pinpointed by random forest and Lasso Cox analysis and confirmed by bioinformatics methods. Then RT-PCR experiments were employed to verify the differences in WNT4 and RPL22L1 gene expressions in tissue samples. The impact of the risk gene on NB cell proliferation, migration, and invasion was confirmed using CCK-8, Wound-healing assay, and Transwell assay. Results PRPH, RPL22L1, ODC1, ALK, NTRK1, ALCAM, and WNT4 were the seven key telomerase prognostic genes that were found by Lasso cox analysis and confirmed by external datasets in NB. Their expression levels varied in INSS stages, age, and high-risk and low-risk groups, as indicated by the validation results. Subsequently, two previously unverified genes, RPL22L1 and WNT4, were selected to construct a multifactor regression model combined with various clinical features to predict the mortality risk. RPL22L1 was ultimately chosen and confirmed to promote NB cell proliferation, migration, and invasion in vitro . Conclusion Telomerase activation is strongly linked to the onset and progression of NB. A multivariate regression model using the genes RPL22L1 and WNT4 proved effective in evaluating the prognosis of NB. The new molecular marker RPL22L1 can inhibit the NB cell proliferation, migration, and invasion, making it beneficial for the early diagnosis of high-risk NB.

Background We previously utilized pretreatment tumor markers Carcinoembryonic Antigen (CEA) and Cancer Antigen 125 (CA125) for predicting lymph node metastasis (LNM) in endometrioid endometrial cancer (EC). Objective The aim of this study was to externally validate a nomogram developed in our previous single-center retrospective study. Methods A multi-center validation study was conducted to recruit endometrioid EC patients from four branches of Chang Gung Memorial Hospital between 2009 and 2021, with patients participating in the original research being excluded. The previously established nomogram was applied with optimal cut-off values for CEA 1.4 ng/ml and CA125 40 U/mL identified through receiver operating characteristic (ROC) curves. The concordance index (C-index) was calculated to assess discrimination, and comparative negative predictive value (NPV) and negative likelihood ratio (NLR) were determined. Decision curve analysis (DCA) was plotted to evaluate our predictive model's clinical utility and net benefit. Results Overall, 1271 patients were included in this external validation study. The results demonstrated a C-index of 0.727, indicating moderate discrimination ability of the nomogram in predicting LNM in this independent cohort. Comparative analysis of NPV 97.2% and NLR 0.36 revealed performance metrics consistent with the original study, reinforcing the nomogram's potential clinical utility in ruling out the possibility of LNM if both pretreatment CEA and CA125 were less than 1.4 ng/ml and 40 U/mL, respectively. The DCA indicated that the nomogram provided clinical utility. Conclusion The reproducible performance metrics in the independent large sample cohort underscore the robustness and generalizability of utilizing CEA and CA125 as predictors of LNM in endometrioid EC, suggesting its potential as a simple tool for clinicians in preoperative decision-making regarding lymphadenectomy.

Background Neuroblastoma (NB) is one of the most common and aggressive pediatric solid tumors, characterized by a highly complex pathogenesis. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) constitute a major cell population and play a pivotal role in facilitating communication among various stromal cells. However, the specific functions and contributions of CAFs in NB remain incompletely understood. Objective To investigate the impact of CAFs-related genes on the prognosis of NB, we developed a risk model to facilitate the diagnosis and prognostication of patients. Methods In this study, a CAFs gene prognostic model for NB was established using single-cell analysis and genomic sequencing data. The effectiveness of this prognostic model was subsequently evaluated through the development of a nomogram, immune infiltration analysis, drug prediction, and gene set enrichment analysis. Ultimately, the expression levels of the identified key genes were experimentally validated in NB tissues. Results A novel prognostic model for CAFs related to NB prognosis was established through single-cell analysis and transcriptome dataset analysis. The prognosis of the high-risk group was worse than that of the low-risk group. The validity of the model was confirmed by nomogram, drug sensitivity analysis, and immune infiltration methods. Finally, the high expression of the key gene STEAP2 in NB tissues was verified by experiments. Conclusions The study introduces a new predictive model that uses CAF markers to forecast the prognosis of NB. STEAP2 plays a key role in identifying high-risk neuroblastoma and may become a potential therapeutic target for NB.

BACKGROUND: Invariant natural killer T (iNKT) cells are an immune subset that purportedly link the adaptive and the innate arms of the immune system. Importantly, iNKT cells contribute to anti-cancer immunity in different types of hematological and solid malignancies by secreting pro-inflammatory cytokines. Therefore, using such cells in treating different type of tumors would be an ideal candidate for cancer immunotherapy.OBJECTIVE: To assess the prognostic effect of iNKT cells across different types of solid and hematological tumors.METHODS: In systematic review and meta-analysis, articles assessed the prognostic effect of iNKT cells were systemically searched using the scientific databases including Google Scholar, ScienceDirect, PubMed, Cochrane Central, and Scopus.RESULTS: Strikingly, the analysis showed the positive impact of intratumoral or circulating iNKT cells on the survival rate in patients with all studied tumors with overall effect of a pooled hazard ratio of 0.89 (95% CI 0.81 to 0.98; 0.01). A highly statistical heterogeneity was noted between studied tumor with I2 87%; 0.00001.CONCLUSIONS: Taken together, this study would present a new insight into the impact of iNKT cells correlate with caner patients’ survival rate and how such cells would be used as a therapeutic target in these patients.

BACKGROUND: Cervical cancer is a prevalent malignancy that significantly contributes to morbidity and mortality rates among women in developing nations. Although the association of KIF18A with various cancers has been established, its role in cervical squamous cell carcinoma (CESC) remains elusive.METHODS: The KIF18A impact on the progression of CESC and its underlying mechanism were investigated through comprehensive bioinformatics analysis utilizing publicly available datasets. The levels of KIF18A and CENPE were assessed in clinical CESC samples through western blotting and qRT-PCR. To discover the role and molecular pathways of KIF18A in CESC, a combination of experimental approaches, including wound-healing, flow cytometry, CCK-8, and Transwell assay, were employed.RESULTS: Our results demonstrate a significant KIF18A expression upregulation in CESC tissues in contrast to healthy tissues. In vitro, KIF18A upregulation was found to enhance cell growth, migration, and invasion and activate the PI3K/AKT signaling pathway while concurrently suppressing apoptosis. Conversely, downregulating KIF18A exhibited contrasting effects. Mechanistically, we observed a positive significant connection between KIF18A and CENPE in CESC cells.CONCLUSION: KIF18A promotes tumor growth in CESC by modulating the PI3K/AKT signaling pathway through regulation of CENPE, making it a potential biomarker for diagnosis and prognosis as well as a therapeutic target.

BACKGROUND: The association between infection with cagA-positive H. pylori and an elevated susceptibility to gastric cancer has been firmly established. PIM2 is known to be overexpressed in various types of cancers; however, the specific mechanism by which cagA influences the regulation of PIM2 expression in gastric cancer remains unidentified at present.MATERIALS AND METHODS: A mutant NCTC11637cagA strain of H. pylori and the eukaryotic expression vector pcDNA-cagA were constructed for evaluating PIM2 expression levels in gastric cancer cells (HGC27, SGC7901, and AG) co-cultured with the NCTC11637 and NCTC11637cagA strain, as well as pcDNA-cagA and the empty vector pcDNA3.1 ().RESULTS: Co-culturing gastric cancer cells with NCTC11637 significantly increased PIM2 expression levels ( 0.001) compared to the negative control group. Additionally, the expression of PIM2 in cells co-cultured with NCTC11637 was higher than that co-cultured with NCTC11637cagA ( 0.001). Furthermore, successful construction of the eukaryotic expression vector pcDNA-cagA resulted in a significant increase in PIM2 mRNA expression levels after its transfection into gastric cancer cells compared to the control group after 48 hours.CONCLUSIONS: The findings indicate that H. pylori/cagA A could be one of the key factors in regulating PIM2 expression levels, potentially influencing the progression of H. pylori-related Gastric Cancer.

BACKGROUND: Endocan was reported to affect breast cancer patients negatively and was able to be detected from patients’ blood.OBJECTIVE: This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers.METHODS: Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3).RESULTS: Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan.CONCLUSIONS: Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.

BACKGROUND: Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking.OBJECTIVE: To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients.METHODS: A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells.RESULTS: Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment.CONCLUSIONS: VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients.

BACKGROUND: Endogenous retroviruses, previously deemed “junk” DNA, have gained attention in recent scientific studies. These inherited genomic elements are now recognized for their potential roles in diseases, especially cancer, highlighting their value as potential diagnostic or therapeutic targets.OBJECTIVE: This research aims to explore the association between human endogenous retroviruses (HERV) and gastric cancer, focusing on discerning HERV expression patterns and understanding their implications in gastric cancer pathology.METHODS: A quantitative analysis of HERV expression was conducted, employing Support Vector Machine (SVM) and AdaBoost algorithms to identify discriminative HERVs. The co-regulation network between protein-coding genes and HERVs was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA).RESULTS: Three distinct HERVs (LTR16A72451, LTR91636874, LTR27D87222) were identified as significantly different. Strong correlations were found between HERVs, and gene sets enriched in the inflammatory pathway.CONCLUSIONS: HERVs appear to influence abnormal inflammatory responses, suggesting a pivotal role in gastric cancer development.

BACKGROUND: The molecular system of receptor activator of nuclear factor kappa- (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment.METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in CAFs and an increased risk of metastasis ( 0.006), shorter metastasis-free survival (MFS) [ 0.007, OR (95%CI) 2.290 (1.259–4.156)], and lower overall survival (OS) [ 0.004, OR (95%CI) 2.469 (1.343–4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs.CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs.