Journal of Cancer最新文献

Background: Previous evidence indicates that the NDC80 complex, a conserved spindle microtubule-binding component of the kinetochore, is overexpressed and associated with prognosis in certain cancer types. Herein, we assessed the expression and prognostic value of NDC80 complex components in pan-cancer and interrogated their potential functions in tumor context through multiple databases and software. Results: Our findings showed that the expression of NDC80 complex components was aberrant across almost all cancer types and correlated positively with poor prognosis at the pan-cancer level. Furthermore, the expression levels of NDC80 complex components were positively associated with Th2 cell infiltration in the majority of cancer types. Additionally, higher expression of the NDC80 complex components was associated with increased immune checkpoint gene expression and TP53 mutation in specific cancer types. We also discovered that NDC80 complex components play pivotal roles in cell division, and the cell cycle within the tumor context. Moreover, knockdown of NDC80 significantly suppressed cell growth and inhibited the G1-S phase transition in two breast cancer cell lines. Conclusions: Our study suggests that the NDC80 complex components could serve as reliable biomarkers for cancer detection and prognosis in pan-cancer, in addition to uncovering their role as cancer-promoting genes involved in Th2 cell infiltration, immune checkpoint, cell growth, and TP53 mutation.

Folate metabolism is a crucial biological process in cell proliferation and exhibits its pro-tumorigenic functions in multiple tumor types. However, its role in pulmonary neuroendocrine carcinomas remains uncertain. Folate metabolism related genes were obtained from previous studies, and the gene expression data and clinical data were collected from GEO database. The expression patterns of folate metabolism related genes were measured across normal and tumor tissues. We subsequently assessed their prognostic role using Kaplan-Meier and univariate Cox regression analysis. The core genes were isolated from 16 prognostic genes through four algorithms. Based on the expression of core genes, patients were divided into two clusters employing consensus clustering algorithm. Furthermore, we evaluated immune infltration level, biological mechanisms, and drug sensitivity. ALDH1L2 was finally identified through qRT-PCR and its pro-tumorigenic function was confirmed via in vitro experiments. The expression patterns of 26 folate metabolism related genes were evaluated between normal lung tissues and PNEC tumor tissues, and 20 of them exhibited differential expression. All of folate metabolism related genes were related to the prognosis of PNECS and 16 genes were identified as prognostic genes. Using SVM-RFE, RF, Xgboost and LASSO algorithm, three core genes were isolated from 16 prognostic genes. Based on the expression patterns of core genes, PNECs patients were divided into two clusters through consensus clustering algorithm. Cluster 1 was characterized by the worse survival, higher immune infiltration level, and sensitivity to chemotherapy. Compared with the HBEC cells, ALDH1L2 was notably overexpressed in NCI-H446 cells (SCLC cell line). ALDH1L2 knockdown significantly repressed the proliferation and migration capacity of tumor cells and increased the cell proportion in S phase. Our results indicated that folate metabolism gene signature is a reliable biomarker for PNECs. Classification based on this signature could be utilized to guide the treatment of PNECs patients and improve its prognosis.

Background: Accurate preoperative evaluation of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for surgeons to make informed decisions regarding appropriate treatment strategies. However, it continues to pose a significant challenge for radiologists. The integration of computer-aided diagnosis utilizing deep learning technology emerges as a promising approach to enhance the prediction accuracy. Methods: This experiment incorporated magnetic resonance imaging (MRI) scans with six different sequences. After a cross-sequence registration preprocess, a deep neural network was employed for the segmentation of hepatocellular carcinoma. The final prediction model was constructed by combining radiomics features with clinical features. The selection of clinical features for the final model was determined through univariate analysis. Results: In this study, we analyzed MRI scans obtained from a cohort of 420 patients diagnosed with HCC. Among them, 140 cases exhibited MVI, while the remaining 280 cases comprised the non-MVI group. The radiomics features demonstrated strong predictive capability for MVI. By extracting radiomic features from each MRI sequence and subsequently integrating them, we achieved the highest area under the curve (AUC) value of 0.794±0.033. Specifically, for tumor sizes ranging from 3 to 5 cm, the AUC reached 0.860±0.065. Conclusions: In this study, we present a fully automatic system for predicting MVI in HCC based on preoperative MRI. Our approach leverages the fusion of radiomics and clinical features to achieve accurate MVI prediction. The system demonstrates robust performance in predicting MVI, particularly in the 3-5 cm tumor group.

Background: Magnetic seed localization is a novel and reliable technique for perioperative localization of non-palpable breast cancers. However, due to susceptibility artifacts, magnetic seeds cannot be in situ during response monitoring of neoadjuvant chemotherapy with MRI. Contrast-enhanced mammography (CEM) could provide an alternative modality for response monitoring while magnetic seeds are in situ. This feasibility study aimed to investigate whether implanted magnetic seeds cause imaging artifacts in CEM examinations. Methods: A phantom experiment and patient studies were conducted to assess the presence of imaging artifacts caused by magnetic seeds on CEM. Chicken breast filet phantoms containing magnetic seeds were imaged using CEM and MRI. Next, twenty women with non-palpable breast tumors scheduled for breast-conserving surgery were included and received a magnetic marker seed preoperatively. Immediately after seed implantation, postprocedural images were taken using the CEM mode on our mammography units. All images were assessed by two experienced breast radiologists for the presence of artifacts. Descriptive statistics were used to present the study results. Results: The phantom experiment revealed no imaging artifacts on CEM, whereas significant artifacts were present on MRI. This allowed us to continue with the patient studies, in which no imaging artifacts associated with magnetic seeds were observed at all. Surgical outcomes demonstrated successful retrieval of all magnetic seeds and negative surgical margins in 19 out of 20 cases. Conclusion: To the best of our knowledge, this is the first study demonstrating that the combination of CEM and magnetic seeds is feasible and does not cause any significant imaging artifacts.

Background: Colon cancer (CC) is a highly prevalent malignancy worldwide, characterized by elevated mortality rates and poor prognosis. N7-methylguanosine (m7G) methylation is an emerging RNA modification type and involved in the development of many tumors. Despite this, the correlation between m7G-related miRNAs and CC remains to be elucidated. This research aimed to investigate the clinical significance of m7G-related miRNAs in predicting both the prognosis and tumor microenvironment (TME) of CC. Method: We retrieved transcriptome data and associated clinical information from a publicly accessible database. Using univariate Cox and LASSO regression analyses, we established a signature of m7G-related miRNAs. Additionally, we used CIBERSORT and ssGSEA algorithms to explore the association between the prognostic risk score and the TME in CC patients. By considering the risk signature and immune infiltration, we identified differentially expressed genes that contribute to the prognosis of CC. Finally, the expression patterns of prognostic miRNAs were verified using quantitative reverse transcriptase PCR (qRT-PCR) in cell lines. Results: We constructed a prognostic risk signature based on seven m7G-related miRNAs (miR-136-5p, miR-6887-3p, miR-195-5p, miR-149-3p, miR-4433a-5p, miR-31-5p, and miR-129-2-3p). Subsequently, we observed remarkable differences in patient outcomes between the high- and low-risk groups. The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.735, 0.707, and 0.632, respectively. Furthermore, our results showed that the risk score can serve as an independent prognostic biomarker for overall survival prediction. In terms of immune analysis, the results revealed a significant association between the risk signature and immune infiltration, as well as immune checkpoint expression. Finally, our study showed that CCDC160 and RLN3 is the gene most relevant to immune cells and function in CC. Conclusion: Our study conducted a comprehensive and systematic analysis of m7G-associated miRNAs to construct prognostic profiles of CC. We developed a prognostic risk model based on m7G-miRNAs, with the resulting risk scores demonstrating considerable potential as prognostic biomarkers. These findings provide substantial evidence for the critical role of m7G-related miRNAs in colon cancer and may offer new immunotherapeutic targets for patients with this disease.

Background: Sulfasalazine, an xCT inhibitor, is being used as a repurposed antineoplastic drug to induce ferroptosis. Ferroptosis is a regulated necrotic cell death pathway that is dependent on iron reserves. Interestingly, cancer stem cells (CSCs) that are regarded as major drivers of resistance to conventional therapies accompanied with tumor relapse and recurrence have bulk amount of iron reserves in the form of ferritin. This suggests that inducing ferroptosis might disrupt stemness and drug-resistant mechanisms in cancer stem cells, thereby reducing the risk of drug-resistance, cancer recurrence, and relapse. Materials & Methods: In the present study, ALDH1A1 expressing oral (OCSCs) and breast (BCSCs) cancer stem cells were sorted and used to investigate the role of sulfasalazine to induce ferroptosis. To check the self-renewability of CSCs spheroid formation, assay was performed and the resultant CSCs were treated with sulfasalazine (SAS) and subjected to gene expression analysis RT-PCR and flow cytometry. FACS was performed to check stem cell marker expression, cell cycle arrest, and apoptosis. Results: Our results suggest that the cells showed a gradual increase in sphere formation till S3 in the case of OCSCs and S2 in the case of BCSCs, with a gradual decrease in sphere-forming efficiency from the respective generations. When treated with 0.6mM SAS, these cells induced ferroptosis by downregulating stem cell markers like ALDH1A1, SLC7A11, ferritin, and GPx-4 with a concomitant increase in transferrin and STEAP-3. Flow cytometry studies revealed that the cells have undergone mitochondrial dysfunction characterized by loss of membrane potential and the cell cycle progression was halted in the G2/M phase. Conclusion: In the present study, we demonstrate that SAS potentially induced ferroptosis accompanied with oxidative stress in both OCSCs as well as BCSCs by lowering GPx-4 activity, a key enzyme that scavenges the products produced as a result of oxidative stress.

Background: Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. Long noncoding RNAs (lncRNAs) have recently gained attention for their pivotal role in regulating cancer progression, including CRC. This study aimed to investigate the biological mechanisms underlying the participation of long intergenic non-protein coding RNA 1134 (LINC01134) in the progression of CRC. Material and Methods: Quantitative Real-time-PCR (RT-qPCR) and western blot were applied to assess the expression levels of mRNA and protein. Functional experiments (CCK8 assay, colon formation assay, EdU assay and flow cytometry) were applied to assess cell viability and apoptosis. RNA-RNA interaction assays, subcellular fractionation analysis and dual luciferase reporter assays were employed to explore molecular interactions between LINC01134 and solute carrier family 1 member 5 (SLC1A5). The mRNA stability was analyzed using actinomycin D (ActD). Results: We found that LINC01134 expression was highly expressed in CRC tissues and positively correlated with advanced clinical stages and unfavorable prognosis, which is consistent with findings from CRC cell lines. Functional experiments showed that suppressing LINC01134 restrained the proliferation of CRC both in vitro and in vivo and induced apoptosis of CRC cells. Gene co-expression analysis revealed a positive relationship between LINC01134 and SLC1A5, which was also upregulated and associated with unfavorable prognosis in CRC. Further analysis of RNA interactions and mRNA stability revealed that LINC01134 directly binds to SLC1A5 mRNA, enhancing its stability. Remarkably, silencing SLC1A5 expression partially counteracted the promotion of CRC cell proliferation by LINC01134 overexpression and alleviated its inhibition of apoptosis. Conclusions: Our findings indicated that LINC01134 functioned as an oncogene in CRC by binding directly to SLC1A5 mRNA and increasing its stability. Therefore, targeting LINC01134 could be a potential therapeutic target for treating CRC.

Background: To improve compliance with endoscopic screening for gastric cancer (GC), we assessed five biomarkers-pepsinogen I (PG I), pepsinogen II (PG II), PG I/II ratio, helicobacter pylori antibody (HP-Ab), and gastrin 17 (G17) - for secondary GC screening by comparing participation and effectiveness of traditional endoscopy and biomarker-based screening in a randomized trial with baseline results. Methods: Seventy-four communities were randomly assigned to traditional endoscopy arm (TEA) or biomarker-based endoscopy arm (BEA). TEA uses a questionnaire for risk assessment, and BEA combines a questionnaire with biomarker detection. High-risk individuals in both arms underwent endoscopic screening. Participation and interim screening effectiveness in two arms were reported with baseline analysis. Results: In total, 5,798 participants in TEA and 5,158 in BEA were recruited, with a participation rate of 26.9%. BEA showed a significantly lower high-risk rate than TEA (15.2% vs. 38.9%) and a higher endoscopic participation rate for high-risk individuals (64.9% vs. 53.0%). The endoscopic screening results showed that there was no significant difference in detection rate of GC abnormalities between the two arms. Education level, frequent drinking, hot, rough and hard food consumption, family history of GC, and history of reflux esophagitis or gastropathy influenced participation rates in biomarker-based screening. Age group, sex and regular consumption of meat, eggs and milk products were associated with stomach abnormalities.Cumulative incidence and specific death rates did not significantly differ in intention-to-screen and per-protocol analyses. Conclusions: Biomarker-based screening effectively identifies high-risk individuals and increases endoscopic participation, providing value insights for improving screening efficiency as a secondary procedure.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southeast Asia, and in the Guangxi and Guangdong provinces of China. The spermatogenic transcription factor zip 1 (SPZ1) is a member of bHLH zip family, and promotes tumorigenesis in the liver, colon and breast tissues. However, the role of SPZ1 in the progression of NPC is unclear. In this study, we found that SPZ1 mRNA and protein levels were significantly upregulated in NPC tissues compared to the normal nasopharyngeal tissues. Furthermore, SPZ1 knockdown in NPC cell lines inhibited proliferation, epithelial-mesenchymal transition, migration, and invasion in vitro, and suppressed tumorigenesis in an in vivo model. On the other hand, SPZ1 overexpression facilitated the growth of NPC cells. Mechanistically, SPZ1-driven progression of NPC is dependent on the Wnt5a/interleukin-6 (IL-6) signaling pathway. Consistent with this, IL-6 levels were significantly increased in NPC tissues and correlated positively with SPZ1 expression. Taken together, our findings suggest that SPZ1 mediates NPC progression through Wnt5a/IL-6 signaling, and the SPZ1/Wnt5a/IL-6 axis is a potential therapeutic target for NPC.

Wilms tumor is a prevalent pediatric tumor influenced by various genetic factors. m⁶A modification is a common nucleotide modification that plays a role in a variety of cancers. As a "reader", YTHDF3 is essential for recognizing m⁶A modifications. However, the association between YTHDF3 gene polymorphisms and Wilms tumor susceptibility has not been previously reported. A five-center case‒control study including 414 patients and 1199 controls was conducted to explore the relationship between YTHDF3 gene polymorphisms and Wilms tumor susceptibility. The samples were genotyped via TaqMan real-time quantitative polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized as indicators to assess their correlation. The YTHDF3 rs2241753 AA genotype was significantly associated with an increased risk of Wilms tumor in females (adjusted OR=1.74, 95% CI=1.05-2.88, P=0.033). The risk of Wilms tumor was also notably elevated in female children with 1-3 risk genotypes (adjusted OR=1.47, 95% CI=1.04-2.07, P=0.028). The YTHDF3 rs2241753 AA genotype and the presence of 1-3 risk genotypes were significantly associated with increased Wilms tumor risk in female children.