Background: This study sought to assess the prognostic factors for leiomyosarcoma (LMS) patients with lung metastasis and construct web-based nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Method: Patients diagnosed with LMS combined with lung metastasis between 2010 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into a training set and a testing set. The X-tile analysis provides the best age and tumor size cut-off point, and changes continuous variables into categorical variables. The independent prognostic factors were determined by Cox regression analysis, and 2 nomograms were established. Receiver operating characteristic curves and calibration curves were used to evaluate the nomograms. Based on the nomograms, 2 web-based nomograms were established. Results: Two hundred and twenty-eight cases were included in the OS nomogram construction, and were randomly divided into a training set (n=160) and a validation set (n=68). Age, T stage, bone metastasis, surgery, chemotherapy, marital status, tumor size, and tumor site were found to be correlated with OS. One hundred and eighty-three cases were enrolled in the CSS nomogram construction, and randomly divided into a training set (n=129) and a validation set (n=54). Age, bone metastasis, surgery, chemotherapy, tumor size, and tumor site were found to be correlated with CSS. Two nomograms were established to predict OS and CSS. In the training set, the areas under the curve of the nomogram for predicting 1-, 2-, and 3-year OS were 0.783, 0.830, and 0.832, respectively, and those for predicting 1-, 2-, and 3-year CSS were 0.889, 0.777, and 0.884, respectively. Two web-based nomograms were established to predict OS (https://wenn23. shinyapps.io/lmslmosapp/), and CSS (https://wenn23.shinyapps.io/lmslmcssapp/). Conclusion:The developed web-based nomogram is a useful tool for accurately analyzing the prognosis of LMS patients with lung metastasis, and could help clinical doctors to make personalized clinical decisions.
Background Osteosarcoma (OS) is a malignant bone tumour of mesenchymal origin. These tumours are characterised by rich vascularisation, therefore promoting rapid proliferation and facilitating metastasis. CD44 has been reported to be involved in OS, but its role and molecular mechanisms in the pathogenesis of the disease are not fully determined. Methods In this study, we investigated the antitumor effect of CD44 on the development of OS and further explored the molecular mechanisms. The expression of CD44, cathepsin S and MMP-9 was detected by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-qPCR) in different cell lines (MG63, U2OS OS and hFOB 1.19). To elucidate the role of CD44 in OS, MG63 and U2OS cells were treated with small interference RNA (siRNA) to knock down CD44, and the knockdown efficiency was validated with GFP and RT-qPCR. Furthermore, cell proliferation was assayed using Cell Counting Kit‑8 (CCK-8) and colony formation assays, and cell migration and invasion were assayed by transwell and wound-healing assays. Results We found that CD44 expression in the MG63 and U2OS OS cell lines was markedly increased compared to that of the human osteoblast hFOB 1.19 cell line. Knockdown of CD44 inhibited proliferation, migration and invasion of MG63 and U2OS cells. Cathepsin S expression in the MG63 and U2OS OS cell lines was increased compared to that of the human osteoblast hFOB 1.19 cell line. When CD44 was knocked down, its expression level went down. Conclusion Taken together, our data reinforced the evidence that CD44 knockdown inhibited cell proliferation, migration and invasion of OS cells accompanied by altered expression of cathepsin S. These findings offer new clues for OS development and progression, suggesting CD44 as a potential therapeutic target for OS.
Background: Studies have shown that the RNA N 6 -methyladenosine (m 6 A) modification patterns are extensively involved in the development of multiple tumors. However, the association between the m 6 A regulator expression patterns and the sarcoma tumor immune microenvironment (TIME) remains unclear. Methods: We systematically evaluated the m 6 A regulator expression patterns in patients with sarcoma based on known 23 m 6 A regulators. Different m 6 A regulator expression patterns were analyzed using gene set variation analysis and a single-sample gene set enrichment analysis algorithm. According to the results of consensus clustering, we classified the patients into four different clusters. Next, we subjected the four clusters to differential genetic analysis and established m 6 A-related differentially expressed genes (DEGs). We then calculated the m 6 A-related DEGs score and constructed the m 6 A-related gene signature, named m 6 A score. Finally, the 259 sarcoma samples were divided into high- and low-m 6 A score groups. We further evaluated the TIME landscape between the high- and low-m 6 A score groups. Results: We identified four different m 6 A modification clusters and found that each cluster had unique metabolic and immunological characteristics. Based on the 19 prognosis-related DEGs, we calculated the principal component analysis scores for each patient with sarcoma and classified them into high- and low-m 6 A score groups. Conclusions: The m 6 A regulator expression patterns and complexity of the sarcoma TIME landscape are closely related to each other. Systematic evaluation of m 6 A regulator expression patterns and m 6 A scores in patients with sarcoma will enhance our understanding of TIME characteristics.
To investigate immune-related long non-coding RNA (irlncRNA) signatures for predicting survival and the immune landscape in melanoma patients. We retrieved gene expression files from The Cancer Genome Atlas and the Genotype-Tissue Expression database and extracted all the long non-coding RNAs from the original data. Then, we selected immune-related long non-coding RNAs (irlncRNAs) using co-expression networks and screened differentially expressed irlncRNAs (DEirlncRNAs) to form pairs. We also performed univariate analysis and Least absolute shrinkage and selection operator (LASSO) penalized regression analysis to identify prognostic DEirlncRNA pairs, constructed receiver operating characteristic curves, compared the areas under the curves, and calculated the optimal cut-off point to divide patients into high-risk and low-risk groups. Finally, we performed multivariate Cox regression analysis, Kaplan–Meier (K–M) survival analysis, clinical correlation analysis, and investigated correlations with tumor-infiltrating immune cells, chemotherapeutic effectiveness, and immunogene biomarkers. A total of 297 DEirlncRNAs were identified, of which 16 DEirlncRNA pairs were associated with prognosis in melanoma. After grouping patients by the optimal cut-off value, we could better distinguish melanoma patients with different survival outcomes, clinical characteristics, tumor immune status changes, chemotherapeutic drug sensitivity, and specific immunogene biomarkers. The DEirlncRNA pairs showed potential as novel biomarkers to predict the prognosis of melanoma patients. Furthermore, these DEirlncRNA pairs could be used to evaluate treatment efficacy in the future.
Aim To explore the application value of modified closed biopsy technique in puncture biopsy of rabbit VX2 transplanted bone tumor model.Methods VX2 tumor was transplanted into the bilateral tibia of 30 rabbits through the tibial plateau to make the model of VX2 transplanted bone tumor. Seven days after modeling, the proximal tibia biopsy was performed under the guidance of X-ray, and the biopsy specimen was examined pathologically. The left leg was biopsied with modified closed biopsy technique (experimental group) and the right leg was biopsied with hollow needle (control group). After 14 days of modeling, all rabbits were killed after X-ray examination around the puncture hole, and the soft tissue around the puncture hole was taken for pathological examination, and the expression levels of PCNA and CD34 in the tissue extract were detected by enzyme-linked immunosorbent assay (ELISA).Results By the end of the experiment, a total of 3 rabbits died, and finally 27 rabbits were included in the study. Tumor cells were detected in all the intramedullary specimens obtained by puncture biopsy. On the 14th day after modeling, X-ray showed that the occurrence rate of periosteal reaction and extraosseous high density shadow around the puncture hole was 14.81% (4/27) in the experimental group and 40.74% (11/27) in the control group. the difference was statistically significant (P<0.05). The pathological results of soft tissue around the puncture hole showed that the tumor cell metastasis rate was 29.63% (8/27) in the experimental group and 100% (27/27) in the control group, and the difference was statistically significant (P<0.05).The expression levels of PCNA and CD34 in the experimental group were lower than those in the control group (P < 0.05). Conclusion Both the modified closed biopsy technique and needle aspiration biopsy can provide sufficient biopsy tissue for the diagnosis of VX2 transplanted bone tumor in rabbits. At the same time, the improved closed biopsy technique has a certain application value in preventing local metastasis of tumor cells along the puncture channel.
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