Female breast cancer (BCa) is the most commonly occurring cancer worldwide. The tumor microenvironment (TME) plays an essential role in tumor invasion, angiogenesis, unlimited proliferation, and even immune escape, but we know little about the TME of BCa. In this study, we aimed to find a TME-related biomarker for BCa, especially for invasive breast carcinoma (BRCA), that could predict prognosis and immunotherapy efficacy. Based on RNA-seq transcriptome data and the clinical characteristics of 1222 samples (113 normal and 1109 tumor samples) from The Cancer Genome Atlas (TCGA) database, we used the ESTIMATE algorithm to calculate the ImmuneScore and StromalScore and then identified differentially expressed genes (DEGs) between the high and low ImmuneScore groups and the high and low StromalScore groups. Thereafter, a protein–protein interaction (PPI) network analysis and univariate Cox regression analyses of overall survival were used to identify potential key genes. Five candidate genes were identified, comprising CD2, CCL19, CD52, CD3E, and ITK. Thereafter, we focused on CD2, analyzing CD2 expression and its association with survival. CD2 expression was associated with tumor size (T stage) to some extent, but not with overall TNM stage, lymph node status (N stage), or distant metastasis (M stage). High CD2 expression was associated with longer survival. METABRIC data were used to validate the survival result (n = 276). Gene set enrichment analysis (GSEA) showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly associated with high CD2 expression were mainly immune-related pathways. Furthermore, CD2 expression was correlated with 16 types of tumor-infiltrating immune cells (TICs). Hence, CD2 might be a novel biomarker in terms of molecular typing, and it may serve as a complementary approach to TNM staging to improve clinical outcome prediction for BCa patients.
22 January 2022 in International Journal of Radiation Oncology, Biology, Physics
Purpose: Temporal muscle thickness (TMT) has been proposed as a novel surrogate marker for skeletal muscle mass in head and neck malignancies. This study investigated the TMT prognostic relevance with gliomas and evaluated the influence of TMT values on survival in patients with gliomas of different grades and IDH subtypes. Methods: The patients’ TMT was measured on contrast-enhanced T1-weighted magnetic resonance images before surgical treatment. Patients were divided into two cohorts based on their median TMT values. The Kaplan–Meier curve was used to compute the overall survival (OS) of different categories and all gliomas. Univariate and multivariate Cox regression analyses were conducted to assess the association between OS and TMT, hematological markers, and other clinical factors in glioma patients. Moreover, the clinical diagnostic efficiency of single and combination biomarkers was evaluated using receiver operating characteristic curve analysis. Results: We retrospectively analyzed 261 patients with newly diagnosed glioma between November 2016 and May 2020 at Hunan Cancer Hospital. Cox analysis indicated that higher TMT (HR 0.286, P< 0.001) and higher KPS score (HR 0.629, P= 0.012) were protective prognostic factors and IDH wildtype status (HR 2.946, P< 0.001), RDW > 12.6 (HR 1.513, P= 0.036), and NLR > 4 (HR 1.560, P= 0.042) were poor prognostic factors for gliomas. Subsequently, patients with thicker TMT were found to have significantly better overall survival (P< 0.001) than patients with thinner TMT among WHO III and WHO IV grade and patients with or without IDH mutation. TMT was considered a better single biomarker than recently prevalent hematological biomarkers for predicting high-grade [0.856 (0.797– 0.916)] and IDH- wild-type [0.864 (0.786– 0.941)] gliomas. Conclusion: This study suggests that TMT is a positive biomarker for clinical prognosis in gliomas and that patients with thicker TMT have greater overall survival for gliomas of different grades and IDH subtypes.
Background: The present study mainly aimed to investigate the direct effects of Endostar (ES) on the proliferation and radiosensitivity of human lung squamous cancer cell line H-520. Results: ES significantly inhibited H-520 cell proliferation in a time- and dose-dependent manner. According to the colony-forming assays, ES could increase the H-520 cell radiosensitivity. ES induced cell apoptosis, the apoptosis rate increased with the raise of ES concentration. Irradiation induced significantly higher apoptosis rate in ES-treated H-520 cells than non-treated H-520 cells. ES induced cell cycle distribution and G0/G1 arrest in H-520 cells, whereas irradiation induced G2/M arrest. The phospho-p38-MAPK and p-Akt protein levels were decreased in H-520 cells after ES treatment. Furthermore, activated caspase protein level increased and Bcl-2 protein levels decreased after treatment with ES and irradiation. Conclusion: ES significantly enhanced the sensitivity of H-520 cells to irradiation by inhibition of cellular proliferation, promotion of cell apoptosis and redistribution of cell cycle, possibly via deactivation of Akt pathway. The present study supports the possibility to use the combination of ES and ionizing irradiation to treat patients with lung squamous cell cancer in clinics.
Background: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. Results: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. Conclusion: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications.
28 November 2024 in International Journal of Radiation Oncology, Biology, Physics