Kupffer Phase Radiomics Signature in Sonazoid-Enhanced Ultrasound is an Independent and Effective Predictor of the Pathologic Grade of Hepatocellular CarcinomaRead the full article
Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.
Chief Editor, Professor Bruno Vincenzi, is an Associate Professor of Medical Oncology at University Campus Bio-Medico, Italy. His research interests include urogenital neoplasms and the pathophysiology and treatment of bone metastases.
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Comprehensive Analysis of LINC01615 in Head and Neck Squamous Cell Carcinoma: A Hub Biomarker Identified by Machine Learning and Experimental Validation
Background. Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients. Methods. We downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration. Results. Cox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells. Conclusion. LINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.
Neferine Exerts Ferroptosis-Inducing Effect and Antitumor Effect on Thyroid Cancer through Nrf2/HO-1/NQO1 Inhibition
Thyroid cancer is the most prevalent endocrine malignancy with an increasing incidence in the past few decades. Neferine possesses various pharmacological activities, which have been applied in diverse disease models, including various tumors. However, the detailed effect and mechanism of neferine on thyroid cancer are still unclear. In the current study, the viability of IHH-4 and CAL-62 cells was examined by the CCK-8 assay. The effect of neferine on the proliferation, apoptosis, invasion, vascular endothelial growth factor (VEGF), epithelial-mesenchymal transition (EMT), and ferroptosis was evaluated by CCK-8, flow cytometry, western blot, and spectrophotometry assays. Mechanically, the expressions levels of Nrf2/HO-1/NQO1 signaling were first determined by a western blot, which was then verified by Nrf2 overexpression. In vivo validation was also conducted on BALB/c nude mice with an inoculation dose of 2 × 106 IHH-4 cells. The results showed that neferine repressed the viability of both IHH-4 and CAL-62 cells both in a dose-dependent way and in a time-dependent fashion, in which the IC50 value of neferine on IHH-4 and CAL-62 cells was 9.47 and 8.72 μM, respectively. Besides, neferine enhanced apoptosis but suppressed invasion, angiogenesis, and EMT of IHH-4 and CAL-62 cells. Moreover, neferine induced the activation of ferroptosis in thyroid cancer cells. Notably, it was revealed that the Nrf2/HO-1/NQO1 pathway was strongly associated with the effect of neferine on the modulation of thyroid cancer. Furthermore, these outcomes were validated in xenografted mice. Therefore, neferine exerted an antitumor effect and ferroptosis-inducing effect on thyroid cancer via inhibiting the Nrf2/HO-1/NQO1 pathway.
Downregulation of LRRC19 Is Associated with Poor Prognosis in Colorectal Cancer
Objective. Colorectal cancer (CRC) is globally one of the most often diagnosed cancers with high mortality rates. This study aimed to explore novel biomarkers for the diagnosis and prognosis of CRC. Methods. We collected 4 datasets about CRC in GEO and sought differentially expressed genes (DEGs) with GEO2R. Leucine-rich repeat-containing protein 19 (LRRC19) expression was assessed through the Oncomine and TIMER database analyses, which was further confirmed by qRT-PCR of CRC samples. We used online survival analysis tools (GEPIA, PrognoScan, and Kaplan–Meier plotter) to examine the prognostic value of LRRC19 in CRC and other malignancies. GO and KEGG enrichment analyses were employed to explore the biological functions of LRRC19. Finally, we conducted network prediction by STRING and further validation on the GEPIA to discover other molecules that might interact with LRRC19. Results. A total of 21 upregulated and 46 downregulated DEGs were identified from the 4 datasets. The TIMER and Oncomine online analyses showed lower mRNA of LRRC19 in CRC tissues compared with adjacent normal tissues, which was validated by qRT-PCR in CRC patient samples. The survival analysis through the GEPIA and PrognoScan websites revealed that low LRRC19 expression was significantly correlated with poor prognosis in CRC patients. The Kaplan–Meier plotter survival analysis indicated that low LRRC19 expression was significantly associated with the disease progression of patients with ovarian cancer, gastric cancer, breast cancer, and lung cancer. The enrichment analysis suggested that low expression of LRRC19 could be involved in the retinol metabolism and the zymogen granule membrane. Through STRING and GEPIA, it was found that LRRC19 is clearly associated with ZCCHC10, MOB3B, IMMP2L, and TRMT11. Conclusion. LRRC19 mRNA was prominently decreased in human CRC tissues and was significantly associated with shorter survival in CRC patients. LRRC19 might serve as a possible target for early diagnosis and prognosis assessment in CRC.
Effects of Vestibular Damage on the Sleep and Expression Level of Orexin in the Hypothalamus of Rats and Its Correlation with Autophagy and Akt Tumor Signal Pathway
The aim of this study was to investigate the effect of vestibular disruption on autophagy-related proteins and the tumour-associated pathway P13K/Akt in rat sleep and its hypothalamus tissue and to examine whether catechins trigger tumour autophagy. Healthy adult male rats were randomly selected and divided into the vestibular damage group, the sham operation group, and the control group, with 8 rats in each group. A vestibular damage model was established through penetrating the tympanic membrane of the external auditory canal by injecting sodium p-aminophenylarsonate. The electroencephalogram (EGG) activity was used to record the sleep-wakefulness cycle of rats, and the expression levels of hypothalamic orexin (orexin) mRNA and autophagy proteins were detected. Primary hippocampal neurons were intervened with orexin at different concentrations and at different times to detect cell viability and the expression of autophagy protein and P13K/Akt signal pathway protein. The results showed that compared with the control group and the sham operation group, NREM duration in the vestibular damage group decreased significantly (), while its W time increased significantly (). The expression level of orexin mRNA in the hypothalamus of the vestibular damage group was significantly higher than that of the other two groups (), the expression of autophagy microtubule-related proteins LC3B and Beclin-1 increased significantly (), and the protein expression level of p62 decreased significantly (). After orexin intervention, compared with the control group, the expression of Beclin-1 protein that positively correlated with autophagy decreased significantly () and the expression of mTOR, PDK1, and Akt protein increased significantly (). Compared with the orexin intervention group, the expression of Beclin-1 and LC3B proteins in cells of the orexin receptor inhibitor (Almorexant) group, the autophagy activator (Rapamycin) group, the orexin + Almorexant group, and the orexin + Rapamycin group increased significantly (), and the expression of mTOR, PDK1, and Akt proteins decreased significantly (). Catechins trigger autophagy in part by regulating the p-Akt/p-mTOR and P13K pathways and by stimulating the MAPK pathway. Catechins initiate apoptosis in common tumour types of hepatocellular carcinoma cells by activating autophagy-related pathways. The conclusion is that vestibular damage can affect the sleep-wakefulness cycle of rats; the level of autophagy in hypothalamic tissue is upregulated and may affect cell proliferation and activity through mTOR-P13K/Akt, which has a certain reference value for tumor formation and provides a basis for the research of insomnia or sleep disorders caused by tumors. Autophagy activation is a key process by which catechins promote apoptosis in tumour cells, providing an avenue for more research on the use of catechins-rich diets for cardiovascular protection in the treatment of tumours.
Pseudogene MSTO2P Interacts with miR-128-3p to Regulate Coptisine Sensitivity of Non-Small-Cell Lung Cancer (NSCLC) through TGF-β Signaling and VEGFC
Background. Coptisine has been widely used for treating a variety of cancer types. To date, whether pseudogene is implicated in coptisine resistance of NSCLC remains unknown. Methods. We performed MTT to assess the cell viability of A549 and Calu-1 cells. The transwell assay was used to examine the invasion of cells. TUNEL was used to determine apoptosis. Results. Our data showed that coptisine treatment suppressed cell viability and invasion of NSCLC cells while contributing to apoptosis. MiR-128-3p negatively regulated MSTO2P. miR-128-3p reverted MSTO2P knockdown-attenuated cell viability and invasion, as well as promoted cell apoptosis of A549 cells. Moreover, we identified TGF-β signaling and VEGFC as key downstream effectors for MSTO2P and miR-128-3p in A549 cells. MiR-128-3p mimic inhibited TGF-β pathway-associated genes (TGFBR1, Smad2, Smad5, and Smad9), whereas miR-128-3p inhibitor exerted opposite effect. MSTO2P knockdown led to attenuated expression levels of TGFBR1, Smad2, Smad5 and Smad9. VEGFC overexpression greatly rescued miR-128-3p-modulated cell viability, invasion, and apoptosis of A549 cells. Conclusion. MSTO2P plays a role in coptisine therapy of NSCLC through miR-128-3p. The findings will advance our understanding of NSCLC treatment.
Albumin Paclitaxel Combined with Intrapleural Infusion of Bevacizumab + Lobaplatin for the Second-Line Treatment of Patients with Non-Squamous Non-Small Cell Lung Cancer
Objective. To investigate the clinical efficacy and safety of albumin paclitaxel combined with intrapleural bevacizumab + lobaplatin for patients with non-squamous non-small cell lung cancer (NS-NSCLC) with malignant pleural effusion (MPE) and analyze prognostic factors. Methods. A total of 126 NS-NSCLC patients were included in the study. Control group with 64 cases received intrapleural infusion of lobaplatin + intravenous albumin paclitaxel, and treatment group with 62 cases received additional intrapleural bevacizumab perfusion. Analysis was performed by collecting data about MPE, progression-free survival (PFS), overall survival (OS), and scores of quality of life. Results. In the treatment and control groups, objective response rate (ORR) was 51.6% and 31.3% (χ2 = 5.39, ), and disease control rate (DCR) was 91.9% and 71.9% (χ2 = 8.49, ), respectively. The main adverse reactions (≥grade 3) in the treatment group were thrombocytopenia, peripheral neurotoxicity, proteinuria, neutropenia, and nausea/vomiting, and in the control group, they were weakness, nausea/vomiting, anemia, and peripheral neurotoxicity. In the control and treatment groups, the median PFS was 6.2 (95% confidence interval (CI): 5.86–6.56) and 5.1 (95% CI: 4.956–5.191), and the median OS was 14.4 (95% CI: 12.681–16.113) and 10.6 months (95% CI: 8.759–12.391). The score of quality of life for treated patients was significantly higher than those before treatment and the control group, and the parameters included general health status (GH), role physical (RP), body pain (BP), social function (SF), and vitality (VT); pH, CD4+/CD8+ values, and vascular endothelial growth factor (VEGF) in the pleural effusion significantly affected the PFS and OS (). Bevacizumab administration in patients with bloody pleural effusion did not increase the risk of pleural hemorrhage. Conclusion. The combination of albumin paclitaxel and intrapleural bevacizumab + lobaplatin is effective and may reverse the adverse events in patients with NS-NSCLC and MPE. The change of CD4+/CD8+ ratio before and after treatment is an independent and prognostic factor for patients with NS-NSCLC and MPE.