RUNX2 is overexpressed in gastric cancer but the mechanism(s) through which it promotes tumor progression remain undefined. Here, we investigated the role of RUNX2 on gastric cancer pathogenesis at the molecular level.The qRT-PCR and western bolt were utilized to examine the mRNA and protein levels. CCK-8, Transwell and wound healing assays were used to measure cell proliferation, invasion and migration. CHIP-PCR gel electrophoresis was used to verify RUNX2 as a transcription factor for MMP13 and MGAT5. The in vivo assay was utilized to assess tumor growth. In vivo assay was used to evaluate tumor growth, aberrant expression of RUNX2 and lung metastasis of gastric cancer.RUNX2 is overexpressed in MKN-45 and AGS cells. Genetic RUNX2 silencing reduced the proliferation, invasion and migration of MKN-45 and AGS cells. Analysis of the gastric cancer samples from the database revealed a significant positive correlation between MGAT5, MMP13, and RUNX2 expression. JASPAR analysis revealed that there was a potential binding site of RUNX2 in the promoter regions of MGAT5 and MMP13, and the experimental results confirmed that RUNX2 could regulate the expression of MGAT5 and MMP13 respectively. In vivo assays confirmed the aberrant expression of RUNX2 in mouse models of gastric cancer and reduced growth and lung metastasis in RUNX2 silenced xenograft tumors assessed.Collectively, these data reveal that RUNX2 enhances MGAT5 and MMP13 expression in gastric cancer cells and represents a biomarker and potential therapeutic target for gastric cancer therapy.
Glucose transporter 1 (GLUT1) plays an important role in the transport and metabolism of glucose in cancer cells. An increasing number of studies have explored the connection between GLUT1 expression and prognosis in non-small cell lung cancer (NSCLC), but the results have been controversial. Therefore, we conducted a meta-analysis to obtain a comprehensive evaluation of the prognostic value of GLUT1 in NSCLC. Relevant studies from PubMed, Embase, and Web of Science were searched. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were used as the effective measures. A total of 10 studies involving 1,665 patients were included in this meta-analysis. The results showed that GLUT1 overexpression was associated with poor overall survival (HR = 2.21; 95% CI, 1.42-3.42; p < 0.001) and disease-free survival (HR = 1.73; 95% CI, 1.35-2.23; p < 0.001). Furthermore, elevated GLUT1 expression correlated with sex (OR = 2.29; 95% CI, 1.17-4.49; p = 0.015), advanced tumor stage (OR = 2.46; 95% CI, 1.79-3.38; p < 0.001), histology (OR = 6.99; 95% CI, 4.71-10.38; p < 0.001), and large tumor size (OR = 2.77; 95% CI, 1.73-4.44; p < 0.001). This meta-analysis revealed overexpression of GLUT1 to be a biomarker of worse prognosis in NSCLC.
With increasingly explored ideologies and technologies for potential applications of artificial intelligence (AI) in oncology, we here describe a holistic and structured concept termed intelligent oncology. Intelligent oncology is defined as a cross-disciplinary specialty which integrates oncology, radiology, pathology, molecular biology, multi-omics and computer sciences, aiming to promote cancer prevention, screening, early diagnosis and precision treatment. The development of intelligent oncology has been facilitated by fast AI technology development such as natural language processing, machine/deep learning, computer vision, and robotic process automation. While the concept and applications of intelligent oncology is still in its infancy, and there are still many hurdles and challenges, we are optimistic that it will play a pivotal role for the future of basic, translational and clinical oncology.
The dynamic changes of N6-methyladenosine controlled by m6A regulators are vital for cancer biology.1 However, the role of m6A regulators in lung adenocarcinoma (LUAD) remains unclear. This study aimed to gain a deeper insight into the roles of m6A regulators in LUAD by bioinformatics.
Methods
31 m6A regulators were retrieved from previous literature. The expression levels of the 31 regulators were investigated by TIMER2.0. The association between the 31 regulators and overall survival (OS) were explored via K-M plotter and Cox regression. Next, mutations status and copy number alterations of the 31 regulators were probed through cBioPortal. Moreover, the interaction between the 31 regulators were revealed via principal component analysis (PCA), protein-protein interaction (PPI), and Metascape enrichment by R programming, STRING 11.5, Cytoscape, and Metascape. Then, the immune microenvironment including immune score, specific immune cells infiltration, and expressions of immune-related gene families were probed via ESTIMATE, TIMER2.0, TIMER, and R programming. Next, LUAD samples were divided into 3 clusters based on the expression patterns of the 31 regulators by k-means method. The differences of OS, gene enrichment, immune microenvironment of the 3 clusters were compared by Log-rank test, GSVA, ESTIMATE, and CIBERSORTx. Moreover, a m6A Score Model was constructed using stepwise regression in this study. The predicting ability of the m6A Score Model was verified by GEO LUAD dataset and TCGA Pan- adenocarcinoma dataset.
Results
22 out of 31 regulators showed differential expression levels between LUAD and normal lung (figure 1). 28 out of 31 regulators were linked with OS (figure 2). The frequency of mutation and copy number alterations were 26.6% and 29.1% respectively (figure 3). PCA revealed the 31 m6A regulators displayed almost completely distinct distribution patterns between LUAD and normal lung (figure 4). PPI and Metascape enrichment indicated the 31 m6A regulators displayed close interrelation (figure 5). Between high and low expression groups of 20, 20 and 29 regulators, tumor purity, immune score, immune cells infiltrations exhibited statistical difference (figure 6). Moreover, 3 clusters displayed distinct OS, gene enrichment, and immune microenvironment (figure 7). Notably, a m6A Score Model was built up upon 15 m6A regulators (figure 8). The model was associated with OS for LUAD and pan-adenocarcinoma (figure 9). Conclusions m6A regulators are associated with molecular features, immune microenvironment and prognosis in LUAD. m6A Score could be used as a reference to immunotherapy and a prognostic index for LUAD.
Reference
Nombela P, Miguel-López B, Blanco S. The role of m6A, m5C and ? RNA modifications in cancer: Novel therapeutic opportunities. Mol Cancer 2021;20:18.
Abstract Background and purpose: This study aims to explore the advantages and robustness of the partial arc combined with prone position planning technique for radiotherapy in rectal cancer patients. Adaptive radiotherapy is recalculated and accumulated on the synthesis CT (sCT) obtained by deformable image registration (DIR) between planning CT and cone beam CT (CBCT). Full and partial volume modulation arc therapy (VMAT) with the prone position on gastrointestinal and urogenital toxicity, based on the probability of normal tissue complications (NTCP) model in rectal cancer patients were evaluated. Materials and methods: Thirty-one patients were studied retrospectively. The contours of different structures were outlined in 155 CBCT images. First, full VMAT (F-VMAT) and partial VMAT (P-VMAT) planning techniques were processed and calculated using the same optimization constraints. The Acuros XB (AXB) algorithm was used in order to generate more realistic dose distributions and DVH, considering the air cavities. Second, the Velocity 4.0 software was used to fuse the planning CT and CBCT to obtain the sCT. Then, the AXB algorithm was used in the Eclipse 13.6 software to conduct re-calculation based on the sCT to obtain the corresponding dose. Furthermore, the LKB NTCP model was used to analyze its radiobiological side effects on the bladder and the bowel bag. Results: With a CTV coverage of 98%, when compared with F-VMAT, P-VMAT with the prone position technique can effectively reduce the mean dose of the bladder and the bowel bag. The LKB NTCP model showed that the P-VMAT combined with the prone planning technique resulted in a significantly lower complication probability of the bladder (1.88±2.08vs1.62±1.41, P=0.041) and the bowel bag (1.77 ± 2.90vs1.57 ± 2.36, P<0.001) than the F-VMAT. In terms of robustness, the P-VMAT is more robust than the F-VMAT, considering the fact that fewer changes were observed in the dose of the CTV, the bladder and the bowel bag. Conclusion: This study analyzed the advantages and robustness of the P-VMAT in the prone position from three aspects, based on the sCT fused by CBCT. Whether it is in regards to dosimetry, radiobiological effects or robustness, P-VMAT in the prone position has shown great advantages.
Abstract Background and purpose This study aims to explore the advantages and robustness of the partial arc combined with prone position planning technique for radiotherapy in rectal cancer patients. Adaptive radiotherapy is recalculated and accumulated on the synthesis CT (sCT) obtained by deformable image registration between planning CT and cone beam CT (CBCT). Full and partial volume modulation arc therapy (VMAT) with the prone position on gastrointestinal and urogenital toxicity, based on the probability of normal tissue complications (NTCP) model in rectal cancer patients were evaluated. Materials and methods Thirty-one patients were studied retrospectively. The contours of different structures were outlined in 155 CBCT images. First, full VMAT (F-VMAT) and partial VMAT (P-VMAT) planning techniques were designed and calculated using the same optimization constraints for each individual patient. The Acuros XB (AXB) algorithm was used in order to generate more realistic dose distributions and DVH, considering the air cavities. Second, the Velocity 4.0 software was used to fuse the planning CT and CBCT to obtain the sCT. Then, the AXB algorithm was used in the Eclipse 15.6 software to conduct re-calculation based on the sCT to obtain the corresponding dose. Furthermore, the NTCP model was used to analyze its radiobiological side effects on the bladder and the bowel bag. Results With a CTV coverage of 98%, when compared with F-VMAT, P-VMAT with the prone position technique can effectively reduce the mean dose of the bladder and the bowel bag. The NTCP model showed that the P-VMAT combined with the prone planning technique resulted in a significantly lower complication probability of the bladder (1.88 ± 2.08 vs 1.62 ± 1.41, P = 0.041) and the bowel bag (1.28 ± 1.70 vs 0.95 ± 1.52, P < 0.001) than the F-VMAT. In terms of robustness, P-VMAT was more robust than F-VMAT, considering that less dose and NTCP variation was observed in the CTV, bladder and bowel bag. Conclusion This study analyzed the advantages and robustness of the P-VMAT in the prone position from three aspects, based on the sCT fused by CBCT. Whether it is in regards to dosimetry, radiobiological effects or robustness, P-VMAT in the prone position has shown comparative advantages.
Abstract For patients with left-sided breast cancer (LBC), postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival and many advanced planning techniques was adopted in PMRT. We aim to use an innovative VMAT technique to enhance the conformity of PTV and reduce the scattering dose of surrounding OARs, thereby reducing the long-term toxicity of the heart as well as ipsilateral lung (IL). The study further analyzes the more appropriate treatment planning techniques for personalized LBC patients with PMRT. 35 LBC patients were retrospectively selected undergoing PMRT. The PTV included lymph nodes, chest walls, excluding internal mammary nodes, where 95% of PTV receiving the prescription dose of 50Gy (2Gy/fraction) with three different techniques, VMAT, IMRT, Hybrid VMAT. Furthermore, the ratio of Heart Volume in Tangent line and heart volume (RHVTL) was proposed to evaluate the relative antonymy position between patient's heart and PTV, which hypothetically represents the complexity of treatment planning. The data from this study showed that for LBC patients undergoing PMRT, the CI from VMAT was 0.85 (IMRT and H-VMAT were 0.77 and 0.83), the heart D mean was 502.9cGy (IMRT and H-VMAT were 675.6cGy and 687cGy) and the V20 of IL was 21.3 as the lowest of the three techniques, but the dose of the contralateral breast (CB) and contralateral lung increased noticeably. In H-VMAT and IMRT, the mean heart dose was significantly related to RHVTL, with R-values of 0.911 and 0.892 respectively, while the values in VMAT was 0.613, thus the VMAT technique was relatively unaffected by the difficulty of treatment plan. For RHVTL values exceed than 0.06, the mean heart dose under VMAT technique raised by 98.7cGy compared to the RHVTL value of less than 0.06, but H-VMAT and IMRT increased by 233cGy and 261.58cGy individually. This study illustrates that separated fields and adjacent fields in VMAT technique obtained the optimal conformality and lowest doses of heart in three techniques for LBC with PMRT. Thus, based on the results of our preliminary study, the VMAT technique is highly recommended when RHVTL is exceeded 0.06.
Prostate cancer (PCa) remains a leading cause of mortality among men in the United States and Western Europe. The molecular mechanism of PCa pathogenesis has not been fully elucidated. In the present study, the expression profile of E2F transcription factor 7 (E2F7) in PCa was examined using immunohistochemistry and reverse transcription‑quantitative PCR, whilst cell cycle progression and apoptosis were determined using fluorescent cell activated sorting techniques. Cell viability was measured using Cell Counting Kit‑8 in loss‑ and gain‑of‑function studies. Dual‑luciferase reporter assay was used to verify if E2F7 was one of the potential targets of miR‑30c. The staining score of E2F7 of PCa tissues was found to be notably higher compared with that of adjacent normal tissues. Suppression of E2F7 expression in PCa cell lines led to significantly reduced proliferation rates, increased proportion of cells in the G1 phase of the cell cycle and higher apoptotic rates compared with those in negative control groups. Dual‑luciferase reporter assay revealed E2F7 to be one of the binding targets of microRNA (miR)‑30c. In addition, transfection of miR‑30c mimics into PCa cells resulted in reduced cell viability, increased proportion of cells in the G1 phase and higher apoptotic rates. By contrast, transfection with the miR‑30c inhibitor led to lower apoptosis rates of PCa cells compared with negative control groups, whilst E2F7 siRNA co‑transfection reversed stimulatory effects of miR‑30c inhibitors on cell viability. In addition, the expression of cyclin‑dependent kinase inhibitor p21 were found to be upregulated by transfection with either E2F7 siRNA or miR‑30c mimics into PCa cells. In conclusion, the present study suggested that E2F7 may be positively associated with PCa cell proliferation by inhibiting p21, whereas E2F7 is in turn under regulation by miR‑30c. These observations suggest the miR‑30c/E2F7/p21 axis to be a viable therapeutic target for PCa.
"BIO22-030: E2F1: A Potential Prognostic Biomarker and Therapeutic Target by Affecting Tumor Development and Immune Microenvironment in LIHC" published on 31 Mar 2022 by National Comprehensive Cancer Network.
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