The Krüppel-like transcription factor 14 (KLF14) is a critical regulator of a wide array of biological processes. However, the role of KLF14 in colorectal cancer (CRC) isn't fully investigated. This study aimed to explore the clinicopathological significance and potential role of KLF14 in the carcinogenesis and progression of CRC. A tissue microarray consisting of 185 samples from stage I-III CRC patients was adopted to analyze the correlation between KLF14 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The underlying mechanisms of altered KLF14 expression on glycolysis were studied using in vitro and patients' samples. The results showed that KLF14 expression was downregulated in CRC than their normal controls. Low KLF14 expression correlated with advanced T stage (P< 0.001) and N stage (P= 0.040), and larger tumor size (P= 0.008). Lost KLF14 expression implied shorter OS and DFS after colectomy in both univariate and multivariate survival analysis (P<0.05). Experimentally, restore KLF14 expression significantly decreased the rate of glycolysis both in vitro and in patients' sample. Mechanically, KLF14 regulated glycolysis by downregulating glycolytic enzyme LDHB. Collectively, KLF14 is a novel prognostic biomarker for survival in CRC, and downregulation of KLF14 in CRC prompts glycolysis by target LDHB. Hence, KLF14 could constitute potential prognostic predictors and therapeutic targets for CRC.
Background: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas. Methods: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated. Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12–30 Gy) in 4 fractions (2–6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40–90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG. Conclusions: Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.
(1) Background: Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies have been reported to have a promising survival benefit in recent studies. Anlotinib is a new oral VEGF receptor inhibitor. This report describes our experience using HSRT and anlotinib for recurrent glioblastoma (rGBM). (2) Methods: Between December 2019 and June 2020, rGBM patients were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. (3) Results: Five patients were enrolled. The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 21 (14–33). The ORR was 100%. Three (60%) patients had the best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). One patient died of tumour progression at the last follow-up. Two patients had grade 2 hand-foot syndrome. (4) Conclusions: Salvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM. A prospective phase II study (NCT04197492) is ongoing to further investigate the regimen.
Early-stage non-small cell lung cancer (NSCLC) patients are at substantial risk of poor prognosis. We attempted to develop a reliable metabolic gene-set-based signature that can predict prognosis accurately for early-stage patients. Least absolute shrinkage and selection operator method Cox regression models were performed to filter the most useful prognostic genes, and a metabolic gene-set-based signature was constructed. Forty-two metabolism-related genes were finally identified, and with specific risk score formula, patients were classified into high-risk and low-risk groups. Overall survival was significantly different between the two groups in discovery (HR: 5.050, 95% CI: 3.368–7.574, P < 0.001), internal validation series (HR: 6.044, 95% CI: 3.918–9.322, P < 0.001), GSE30219 (HR: 2.059, 95% CI: 1.510–2.808, P < 0.001), and GSE68456 (HR: 2.448, 95% CI: 1.723–3.477, P < 0.001). Survival receiver operating characteristic curve at the 5 years suggested that the metabolic signature (area under the curve [AUC] = 0.805) had better prognostic accuracy than any other clinicopathological factors. Further analysis revealed the distinct differences in immune cell infiltration and tumor purity reflected by an immune and stromal score between high- and low-risk patients. In conclusion, the novel metabolic signature developed in our study shows robust prognostic accuracy in predicting prognosis for early-stage NSCLC patients and may function as a reliable marker for guiding more effective immunotherapy strategies.
Background: The optimal treatment for recurrent high-grade gliomas (rHGG) remains uncertain. This research aimed to investigate the efficacy and safety of CyberKnife radiosurgery as a salvage treatment for high-grade gliomas at first recurrence that within the radiation field.Methods: Between January 2016 and October 2019, rHGG patients treated with CyberKnife radiosurgery were retrospectively analyzed. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and toxicity. Toxicity was assessed using CTCAE 5.0. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) were evaluated.Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis Glioblastoma (GBM), and rest (21) were WHO Grade 3 Gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). Median baseline Karnofsky Performance Status (KPS) is 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas; p = 0.039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed concurrent bevacizumab with radiosurgery and KPS>70 were favorable prognostic factors for grade 4 patients.Conclusions: Salvage CyberKnife radiosurgery showed a favorable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of HSRS in rHGG.
Background: The optimal treatment for recurrent high-grade gliomas (rHGG) remains uncertain. This study aimed to investigate the efficacy and safety of CyberKnife radiosurgery as a salvage treatment for in field recurrence of high-grade gliomas at first time.Methods: Between January 2016 and October 2019, seventy patients with rHGG undergone CyberKnife radiosurgery were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events which was according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) were evaluated.Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81 – 121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). Median baseline of Karnofsky Performance Status (KPS) is 70 (40 - 90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS>70 were favorable prognostic factors for grade 4 patients with HGG.Conclusions: Salvage CyberKnife radiosurgery showed a favorable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.