Caixing Sun

Advances in molecular biology have extended survival for lung cancer patients with brain metastases. However, radiotherapy and surgery remain standard for non-small cell lung cancer (NSCLC) brain metastases. Existing studies assess surgical and radiotherapeutic outcomes using outdated data and lack relevant subgroup analyses. We retrospectively analyzed 298 NSCLC patients with 1–3 brain metastases. Overall survival (OS) and median OS were compared across five treatments: surgery + postoperative radiotherapy, surgery + postoperative non-radiotherapy, whole brain radiotherapy, stereotactic radiosurgery (SRS), and whole brain radiotherapy + SRS. Univariate and multivariate Cox regression analyses were conducted. Significant survival differences were noted among treatments (p = 0.0041) for patients with 1–3 brain metastases, single metastasis (p = 0.0034), age > 57 (p = 0.0001), wild-type EGFR/ALK (p = 0.0017), KPS ≥ 90 (p = 0.0379), tumor diameter ≤ 2.7 cm (p = 0.0147), and no extracranial metastasis (p = 0.0014). Surgery + postoperative radiotherapy and SRS significantly improved OS and median OS. For KPS ≥ 90, surgery + postoperative radiotherapy improved OS. Multivariate analysis identified age ≤ 57 (HR: 1.89; p < 0.001), surgery + postoperative radiotherapy (HR: 0.60; p = 0.017), and SRS (HR: 0.57; p = 0.01) as independent protective factors for OS. Surgery + postoperative radiotherapy and SRS enhance survival in NSCLC patients with 1–3 brain metastases, particularly those with wild-type EGFR/ALK, small metastases, and no extracranial metastases. For KPS ≥ 90, surgery followed by radiotherapy is recommended. SRS improves median OS in patients with KPS ≤ 80.

Background: Brain metastases are crucial in cancer progression, requiring focused efforts on the screening, early detection, and treatment. However, accurate forecasting the postoperative prognosis of patients with non-small cell lung cancer brain metastasis remains a challenge. This retrospective study aims to discern the factors that influence the prognosis of such patients. Methods: A total of 151 cases from Zhejiang Cancer Hospital were collected. Univariate analysis was conducted using Kaplan-Meier and Log-rank test, while multivariate analysis was performed using Cox proportional hazards regression model. Student’s t-test and chi-square test were employed to examine the differences between the long-term survival and the short-term survival groups. Ultimately, a predictive model was constructed using R 4.2.1. Results: Univariate analysis identified 12 factors as prognostic factors, showing statistical significance. In multivariate analysis, the primary contributing factors to survival were identified as age, chemotherapy of brain metastases, pathology, surgery of nonsmall cell lung cancer, targeted drugs, and GPA score. Comparing long-term and short-term groups, age, pathology, surgery of lung, targeted therapy, and radiotherapy of brain metastases were statistically differentiating factors. Based on multivariate analysis, we established a clinical predictive model predicting 2-year, 3-year, and 5-year survival rates. Conclusion: Younger age, receiving chemotherapy for brain metastases, adenocarcinoma pathology, lung cancer surgery, targeted therapy, and a high GPA score are associated with longer survival. This model predicts the survival period for patients with non-small cell lung cancer brain metastasis after surgery and helps in selecting more effective treatment plans.

Circular RNAs (circRNAs) play an important role in cancer development by sponging microRNAs (miRNAs) to regulate the signaling axis. However, more comprehensive mechanisms of circRNAs in glioblastoma need to be elucidated.RT-qPCR was used to detect the expression levels of circRNA-SMO and miR-326. Dual-luciferase reporter assays were conducted to verify the interaction among circRNA-SMO, miR-326, and CEP85. Flow cytometric analysis was performed to detect apoptosis. Western blotting was used to determine the protein levels of the different molecules. Animal xenograft experiments were performed to evaluate the role of circRNA-SMO in vivo.CircRNA-SMO was upregulated in glioblastoma tissues and glioblastoma cells. CircRNA-SMO downregulation inhibited the viability and colony-forming ability of the glioblastoma cells. In addition, miR-326 was downregulated in glioblastoma cells, which was verified to sponge circRNA-SMO and interact with CEP85. Moreover, circRNA-SMO inhibition induced the elevation of miR-326 and apoptosis, accompanied by a decrease in CEP85. CircRNA-SMO knockdown-mediated tumor inhibition was prevented by an miR-326 inhibitor. Furthermore, circRNA-SMO inhibition inhibited tumor growth in vivo, accompanied by an increase in miR-326 and a decline in CEP85 in tumor tissues.Conclusions. CircRNA-SMO sponges miR-326 to promote glioblastoma proliferation and migration by upregulating CEP85 expression. This study clarified the role of circRNA-SMO in the development of glioblastoma, providing novel insights for its treatment.

Background. Glioma is a common tumor that originated from the brain, and molecular targeted therapy is one of the important treatment modalities of glioma. Apatinib is a small‐molecule tyrosine kinase inhibitor, which is widely used for the treatment of glioma. However, the underlying molecular mechanism has remained elusive. Recently, emerging evidence has proved the remarkable anticancer effects of ferroptosis. In this study, a new ferroptosis‐related mechanism of apatinib inhibiting proliferation of glioma cells was investigated, which facilitated further study on inhibitory effects of apatinib on cancer cells. Methods. Human glioma U251 and U87 cell lines and normal astrocytes were treated with apatinib. Ferroptosis, cell cycle, apoptosis, and proliferation were determined. A nude mouse xenograft model was constructed, and tumor growth rate was detected. Tumor tissues were collected to estimate ferroptosis levels and to identify the relevant pathways after treatment with apatinib. Results. Treatment with apatinib could induce loss of cell viability of glioma cells, but not of normal astrocytes, through eliciting ferroptosis in vitro and in vivo. It was also revealed that apatinib triggered ferroptosis of glioma cells via inhibiting the activation of nuclear factor erythroid 2‐related factor 2/vascular endothelial growth factor receptor 2 (Nrf2/VEFGR2) pathway. The overexpression of Nrf2 rescued the therapeutic effects of apatinib. Conclusion. Our study proved that treatment with apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib.

Epigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. m⁶A methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The m⁶A modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the m⁶A methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of m⁶A methylation are reviewed, especially the role of m⁶A methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of m⁶A deposition.

Glioma is one of the most common primary brain tumors, and is divided into low-grade and high-grade gliomas. Long non-coding RNAs have been increasingly implicated in the pathogenesis and prognosis of glioma. Here, we demonstrated that the long non-coding RNA TP73-AS1 is differentially expressed among gliomas with different clinicopathological features in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and GEO glioma datasets; high expression of TP73-AS1 was associated with poor clinical features, including age, stage, IDH mutation status, 1p/19q co-deletion status and overall survival. Measuring TP73-AS1 expression using real-time PCR showed the same result for 76 glioma tissue samples from our hospital. The infiltration levels of various immune cells in the tumor microenvironment were found to be significantly higher in patients with high expression of TP73-AS1. Taken together, our results suggest that TP73-AS1 has potential as a prognostic glioma biomarker. Moreover, the knowledge that TP73-AS1 affects the glioma immune microenvironment may provide new information for the immunological research and treatment of glioma.

Background: High-grade glioma (HGG) and solitary brain metastasis (sBM) patients show similar symptoms in clinical practice, and accurately differential diagnosis directly affects the management and prognosis of patients. The aim of this study was to distinguish two entities by preoperative serum beta 2-microglobulin (beta 2-m) and routine blood test-associated inflammatory indexes including, white blood cell (WBC), neutrophils, lymphocytes, mono-cytes, and platelets count, red cell distribution width (RDW), platelet distribution width (PDW), neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR). Patients and Methods: A retrospective analysis was performed in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to December 2019, including 127 patients of newly pathologically diagnosed with HGG and 174 patients with sBM. Clinical information including age, gender, pathological diagnosis, preoperative serum beta 2-m and routine blood tests were collected, and NLR and MLR were calculated. The diagnostic significance of these markers for HGG and sBM was assessed by receiver operating characteristic (ROC) curves. Results: The patients with sBM had significantly higher values of preoperative age, beta 2-m, NLR and MLR as well as lower lymphocytes count than patients with HGG. Besides, the area under the curve (AUC) in differentiating HGG from sBM was 0.625 (95%CI: 0.561-0.689) for age, 0.655 (0.594-0.717) for beta 2-m, 0.634 (0.571-0.698) for NLR and 0.622 (0.559-0.686) for MLR, and the combination of Age+beta 2-m+NLR+MLR showed the best diagnostic performance with AUC of 0.731 (0.675-0.788) and 0.048*Age+0.001*beta 2-m +0.201*NLR+0.594*MLR>5.813 could indicate sBM rather than HGG. Conclusion: The Age+beta 2-m+NLR+MLR combination was revealed as an inexpensive and noninvasive biomarker for differentiating between HGG and sBM before surgery.

Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions. We conducted a pooled analysis to evaluate the diagnostic accuracy of FNA-Tg and searched electronic databases for original articles in English from 1993 through 2017. Finally, a total of 22 studies containing 2,670 lymph nodes (LNs) that enrolled participants with suspicious neck LNs during thyroid nodule workup or papillary thyroid cancer (PTC) follow-up were included. In our analysis, the overall pooled sensitivity for FNA-Tg was 0.91 (95%CI: 0.87–0.93), specificity was 0.94 (95% CI: 0.91–0.96). Meta regression revealed that the cutoff value and status of serum Tg were sources of heterogeneity for sensitivity, and the cutoff value was source of heterogeneity for specificity. Additionally, the cutoff value and status of serum Tg were sources of heterogeneity in the joint model. Subgroup analysis about cut-off value showed that the choice of 1 ng/mL had highest sensitivity, 40 ng/mL had highest specificity. At last, we arrived at the conclusion that FNA-Tg measurement had high specificity and sensitivity in the early detection of LNs metastases from PTC by our meta-analysis. The technique was simple and could be recommended to apply in any FNA facility, especially when LN were small-sized. Significantly, a better standardization of criteria for FNA-Tg detection and cutoff value was required to provide useful data and to improve management of PTC patients in the future.

Long non‐coding RNAs have recently become a key regulatory factor for cancers, whereas FER1L4, a newly discovered long non‐coding RNA, has been mostly studied in gastric carcinoma and colon cancer cases. The functions and molecular mechanism of FER1L4 have been rarely reported in glioma malignant phenotypes. In this study, it was found that the expression of LncRNA FER1L4 is upregulated in high‐grade gliomas than in low‐grade cases and that a high expression of LncRNA FER1L4 predicts poor prognosis of gliomas. Meanwhile, in vitro study suggests that expression of FER1L4 with SiRNA knockdown obviously suppresses cell cycle and proliferation. It is further demonstrated by experiments that the FER1L4 knockdown suppresses growth of in vivo glioma. Besides, it is found in our study that LncRNA FER1L4 expression is positively correlated with E2F1 mRNA expression. After knockdown of FER1L4 expression, E2F1 expression is significantly down‐regulated, whereas the expression of miR‐372 is significantly up‐regulated; the up‐regulation of miR‐372 leads to significant down‐regulation of FER1L4 and E2F1 expression. In addition, it is also found that FER1L4 can be used as competitive endogenous RNA to interact or bind with miR‐371 and thereby up‐regulate E2F1, thus promoting the cycle and proliferation of glioma cells. It may be one of the molecular mechanisms in which FER1L4 plays its oncogene‐like role in gliomas.