Gastric cancer (GC) has a high morbidity and mortality rate, with peritoneal metastasis (PM) identified as the main site of metastasis. Our previous study found that FNDC1 has a higher frequency of mutations in patients with PM by high-throughput sequencing assay, suggesting that it may be associated with GC invasion and PM, however the specific mechanism remains unclear.

Epidermal growth factor-like domain 7 (EGFL7) is a protein specifically secreted by blood vessel endothelial cells, which plays an important role in angiogenesis. Considering the aberrant secretion of EGFL7 in osteosarcoma (OS) has not yet been elucidated, this study investigated the secretion of EGFL7 in OS and the changes in its secretion after chemotherapy. We observed increased varying secretion of EGFL7 in OS tissues compared with chondrosarcoma (CS) tissues. OS cell lines and HUVECs showed higher EGFL7 mRNA and protein expression than SW1353, with OS cells expressing the highest levels. In patient samples, EGFL7 was highly expressed in the cytoplasm of OS tumor cells and vascular endothelium cells. This overexpression was abolished in OS cell and tumor tissues when treated with chemotherapy. This study is a pioneering study to investigate EGFL7 expression and localization in human OS tissues and cell. Overexpression of EGFL-7 in response to chemotherapy suggests that it can be used as a therapeutic target for OS.

Medulloblastoma (MB) is a highly heterogeneous and one of the most malignant pediatric brain tumors, comprising four subgroups: Sonic Hedgehog, Wingless, Group 3, and Group 4. Group 3 MB has the worst prognosis of all MBs. However, the molecular and cellular mechanisms driving the maintenance of malignancy are poorly understood. Here, we employed high-throughput single-cell and bulk RNA sequencing to identify novel molecular features of Group 3 MB, and found that a specific cell cluster displayed a highly malignant phenotype. Then, we identified the glutamate receptor metabotropic 8 (GRM8), and AP-1 complex subunit sigma-2 (AP1S2) genes as two critical markers of Group 3 MB, corresponding to its poor prognosis. Information on 33 clinical cases was further utilized for validation. Meanwhile, a global map of the molecular cascade downstream of the MYC oncogene in Group 3 MB was also delineated using single-cell RNA sequencing. Our data yields new insights into Group 3 MB molecular characteristics and provides novel therapeutic targets for this relentless disease.

Soft tissue sarcomas on extremities with regional lymph nodes metastasis (STSE-RLNM) is a devastating situation. Optimizing therapeutic approaches is vital but hampered by a shortage of randomized trials. We used a population-level database to evaluate radiotherapy's impact on sarcoma-specific survival (SSS) and overall survival (OS) for surgery for STSE-RLNM.

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m6A) methylation modification reportedly plays roles in immune response. The relationship between the m6A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m6A modification pattern and m6A-related signatures based on 21 regulators. Thereafter, the m6A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients' clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m6A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m6A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m6A regulators and specific immune cell infiltration was demonstrated in our study and the m6A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m6A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m6A-related signatures.

Background and Purpose: Evidence for induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) in nasopharyngeal carcinoma (NPC) was derived from landmark clinical trials excluding the T3N0, T3N1, T4N0 subgroups. This study used Epstein-Barr virus (EBV) DNA to select IC beneficiaries from the three subgroups. Materials and Methods: Significant predictors of overall survival (OS) were identified using multivariate Cox analyses. Risk stratification was generated using recursive partitioning analysis (RPA). IC+CCRT was compared with CCRT in each risk stratification and in different subgroups. Individual-level data from a clinical trial (NCT01245959) was used for validation. Results: Gender and EBV DNA were included in RPA-generated risk stratification, categorizing patients into low-risk (EBV DNA <2,000 copies/mL; female and EBV DNA ≥2,000 copies/mL) and high-risk groups (male and EBV DNA ≥2,000 copies/mL). The OS superiority of IC+CCRT over CCRT was only observed in the high-risk group (HR = 0.64, 95% CI = 0.43-0.97; P = 0.032). Subgroup analysis indicated the OS benefit was exclusively from the docetaxel-cisplatin-5-fluorouracil regimen (HR = 0.41, 95% CI = 0.22-0.78; P = 0.005). The status of the T3N1 subgroup as an IC beneficiary is more explicit than the T3N0 and T4N0 subgroups. IC+CCRT showed improved OS in the validation cohort combining high-risk cases of real-world data with clinical trial data (HR = 0.62, 95% CI = 0.42-0.94; P = 0.023). Conclusion: Patients with high-risk T3N1 NPC is the definite target population for receiving IC+CCRT in real-world practice. T3N0 and T4N0 subgroups need further investigations in future IC-related studies.

Aims: This study aimed to compare and evaluate the oncological and functional prognosis of two surgical approaches for giant cell tumor of the bone (GCTB) around the knee joint and provide worthy suggestion for clinical treatment. Patients and Methods: This study included 93 patients, who were divided into the extended curettage (EC) group and segmental resection (SR) group. Relevant preoperative and postoperative data were collected, oncological and functional prognosis were evaluated, and postoperative complications of the two groups were analyzed. Local recurrence was assessed via clinical and radiological tests. Functional prognosis was evaluated using the Musculoskeletal tumor Society (MSTS) scoring system. Results: The EC group had 69 patients; it included 57 primary cases and 12 recurrent cases. The SR group had 24 patients (12 men and 12 women; mean age, 34.9 years), including 15 primary cases and 9 recurrent cases. In this study, six cases (6.5%; EC group, 5 cases; SR group 1 case) recurred within 18 months postoperatively. There was a significant difference in the mean MSTS score between the two groups (p < 0.001). Nononcologic complications occurred frequently in the EC group than in the SR group (28.0 vs. 16.7%), but no complications had serious consequences, and the functional prognosis was not affected. Conclusion: EC and SR for GCTB around the knee joint can achieve satisfactory oncological prognosis, but we should individually select the most suitable surgical method according to Campanacci grade, age, and long-term complications of patients and consider the functional prognosis to ensure excellent oncological prognosis.

Gliomas are characterized by high morbidity and mortality, and have only slightly increased survival with recent considerable improvements for treatment. An innovative therapeutic strategy had been developed via inducing ROS-dependent cell death by targeting antioxidant proteins. In this study, we found that glioma tissues expressed high levels of superoxide dismutase 1 (SOD1). The expression of SOD1 was upregulated in glioma grade III and V tissues compared with that in normal brain tissues or glioma grade I tissues. U251 and U87 glioma cells expressed high levels of SOD1, low levels of SOD2 and very low levels of SOD3. LCS-1, an inhibitor of SOD1, increased the expression SOD1 at both mRNA and protein levels slightly but significantly. As expected, LCS-1 caused ROS production in a dose- and time-dependent manner. SOD1 inhibition also induced the gene expression of HO-1, GCLC, GCLM and NQO1 which are targeting genes of nuclear factor erythroid 2-related factor 2, suggesting the activation of ROS signal pathway. Importantly, LCS-1 induced death of U251 and U87 cells dose- and time-dependently. The cell death was reversed by the pretreatment of cells with ROS scavenges NAC or GSH. Furthermore, LCS-1 decreased the growth of xenograft tumors formed by U87 glioma cells in nude mice. Mechanistically, the inhibition of P53, caspases did not reverse LCS-1-induced cell death, indicating the failure of these molecules involving in cell death. Moreover, we found that LCS-1 treatment induced the degradation of both PARP and BRCA1 simultaneously, suggesting that LCS-1-induced cell death may be associated with the failure of DNA damage repair. Taking together, these results suggest that the degradation of both PARP and BRCA1 may contribute to cell death induced by SOD1 inhibition, and SOD1 may be a target for glioma therapy.

Glioblastoma (GBM) stem cells are resistant to cancer therapy, and therefore responsible for tumor progression and recurrence after conventional therapy. However, the molecular mechanisms driving the maintenance of stemness and dedifferentiation are poorly understood. In this study, we identified plant homeodomain finger-containing protein 20 (PHF20) as a crucial epigenetic regulator for sustaining the stem cell-like phenotype of GBM. It is highly expressed in GBM and tightly associated with high levels of aggressiveness of tumors and potential poor prognosis in GBM patients. Knockout of PHF20 inhibits GBM cell proliferation, as well as its invasiveness and stem cell-like traits. Mechanistically, PHF20 interacts with WDR5 and binds to the promoter regions of WISP1 for its expression. Subsequently, WISP1 and BGN act in concert to regulate the degradation of β-Catenin. Our findings have identified PHF20 as a key driver of GBM malignant behaviors, and provided a potential target for developing prognosis and therapy.

Serpin family D member 1 (SERPIND1) belongs to the serine protease inhibitor family. Its role in cancers has gradually attracted interest from researchers in recent years. However, the role of SERPIND1 in the development of epithelial ovarian cancer remains poorly understood. This studied aimed to investigate the expression and clinical significance of SERPIND1 in epithelial ovarian cancer, as well as its effect on the malignant biological behavior of ovarian cancer cells and the related regulatory mechanisms. We found that SERPIND1 expression was significantly elevated in epithelial ovarian cancer. Patients with higher expression of SERPIND1 in ovarian cancer tissues had poor prognoses. SERPIND1 promoted the proliferation, migration, invasion, G1-to-S phase transition, and epithelial-mesenchymal transition of ovarian cancer cells and inhibited their apoptosis by promoting phosphorylation in the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Meanwhile, the inhibition of SERPIND1 expression in ovarian cancer cells resulted in opposite effects. The addition of the PI3K/AKT pathway inhibitor LY294002 to SERPIND1-overexpressing cells could reverse the promoting effect of SERPIND1 on the malignant biological behavior of ovarian cancer cells. Further, nuclear factor kappa B subunit 1, a transcription factor could bind to the promoter region of SERPIND1 and regulate SERPIND1 expression. In conclusion, our results indicated that SERPIND1 could be an effective marker for assessing the prognosis of ovarian cancer. By elucidating its mechanism underlying the promotion of malignant biological behavior of ovarian cancer by SERPIND1, we demonstrated that SERPIND1 could potentially serve as a novel drug target.

Immune evasion in glioma strongly correlates with clinical outcomes; however, the molecular mechanisms driving the maintenance of immunosuppression remain largely unknown. Recently studies demonstrate that Klothos are aberrantly expressed in several cancers and are potential therapeutic targets in cancers. However, their roles are still unclear in glioma. Here, we show that LCTL is highly expressed in gliomas and that its expression is regulated by DNA methylation status at the promoter. LCTL expression is also found to be significantly associated with high tumor aggressiveness and poor outcomes for glioma patients. Mechanistically, results suggested that LCTL might play an important immunosuppressive role by recruiting immunosuppressive cells and regulating tumor-associated macrophages polarization, T cell exhaustion, and epithelial-mesenchymal transition through FGF signaling in glioma. Our results establish LCTL as a key biomarker for prognosis that could be considered a potential epigenetic and immunotherapeutic target for treatment.