Table_2_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.xlsx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

DataSheet1_Development of a Novel Sphingolipid Signaling Pathway-Related Risk Assessment Model to Predict Prognosis in Kidney Renal Clear Cell Carcinoma.PDF

This study aimed to explore underlying mechanisms by which sphingolipid-related genes play a role in kidney renal clear cell carcinoma (KIRC) and construct a new prognosis-related risk model. We used a variety of bioinformatics methods and databases to complete our exploration. Based on the TCGA database, we used multiple R-based extension packages for data transformation, processing, and statistical analyses. First, on analyzing the CNV, SNV, and mRNA expression of 29 sphingolipid-related genes in various types of cancers, we found that the vast majority were protective in KIRC. Subsequently, we performed cluster analysis of patients with KIRC using sphingolipid-related genes and successfully classified them into the following three clusters with significant prognostic differences: Cluster 1, Cluster 2, and Cluster 3. We performed differential analyses of transcription factor activity, drug sensitivity, immune cell infiltration, and classical oncogenes to elucidate the unique roles of sphingolipid-related genes in cancer, especially KIRC, and provide a reference for clinical treatment. After analyzing the risk rates of sphingolipid-related genes in KIRC, we successfully established a risk model composed of seven genes using LASSO regression analysis, including SPHK1, CERS5, PLPP1, SGMS1, SGMS2, SERINC1, and KDSR. Previous studies have suggested that these genes play important biological roles in sphingolipid metabolism. ROC curve analysis results showed that the risk model provided good prediction accuracy. Based on this risk model, we successfully classified patients with KIRC into high- and low-risk groups with significant prognostic differences. In addition, we performed correlation analyses combined with clinicopathological data and found a significant correlation between the risk model and patient’s M, T, stage, grade, and fustat. Finally, we developed a nomogram that predicted the 5-, 7-, and 10-year survival in patients with KIRC. The model we constructed had strong predictive ability. In conclusion, we believe that this study provides valuable data and clues for future studies on sphingolipid-related genes in KIRC.</p

Presentation_1_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.pptx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

Table_1_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.xlsx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

Table_5_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.xlsx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

Image5_Potential Application of Pyroptosis in Kidney Renal Clear Cell Carcinoma Immunotherapy and Targeted Therapy.TIF

Renal cell carcinoma (RCC) is a type of cancer with an increasing rate of morbidity and mortality and is a serious threat to human health. The treatment of RCC, especially kidney renal clear cell carcinoma (KIRC), has always been the focus of clinical treatment. Using The Cancer Genome Atlas (TCGA) database as a starting point, we explored the feasibility of applying the pyroptosis mechanism to KIRC treatment by searching for cancer markers associated with pyroptosis and cancer treatment signatures. The obtained samples were clustered using unsupervised clustering analysis to define the different KIRC subtypes with different pyroptosis expression levels. Based on this, a gene expression analysis was performed to explore the carcinogenic mechanism that is markedly related to pyroptosis. The Genomics of Drug Sensitivity in Cancer database and single sample gene set enrichment analysis (ssGSEA) algorithm were used to analyze the different treatment methods of the current prominent KIRC to determine whether pyroptosis plays a role. Finally, LASSO regression was used to screen for related genes and construct a model to predict patient prognosis. The expression levels of GSDME, CASP3, CASP4, CASP5, CHMP3, and CHMP4C were incorporated into the model construction. After verification, the prediction accuracy of the 3-, 5-, 7- and 10 years survival rates of our prognostic model were 0.66, 0.701, 0.719, and 0.728, respectively. Through the above analysis, we demonstrated the feasibility of pyroptosis in the clinical treatment of KIRC and provided novel ideas and suggestions for the clinical treatment of KIRC.</p

Image2_Potential Application of Pyroptosis in Kidney Renal Clear Cell Carcinoma Immunotherapy and Targeted Therapy.TIF

Renal cell carcinoma (RCC) is a type of cancer with an increasing rate of morbidity and mortality and is a serious threat to human health. The treatment of RCC, especially kidney renal clear cell carcinoma (KIRC), has always been the focus of clinical treatment. Using The Cancer Genome Atlas (TCGA) database as a starting point, we explored the feasibility of applying the pyroptosis mechanism to KIRC treatment by searching for cancer markers associated with pyroptosis and cancer treatment signatures. The obtained samples were clustered using unsupervised clustering analysis to define the different KIRC subtypes with different pyroptosis expression levels. Based on this, a gene expression analysis was performed to explore the carcinogenic mechanism that is markedly related to pyroptosis. The Genomics of Drug Sensitivity in Cancer database and single sample gene set enrichment analysis (ssGSEA) algorithm were used to analyze the different treatment methods of the current prominent KIRC to determine whether pyroptosis plays a role. Finally, LASSO regression was used to screen for related genes and construct a model to predict patient prognosis. The expression levels of GSDME, CASP3, CASP4, CASP5, CHMP3, and CHMP4C were incorporated into the model construction. After verification, the prediction accuracy of the 3-, 5-, 7- and 10 years survival rates of our prognostic model were 0.66, 0.701, 0.719, and 0.728, respectively. Through the above analysis, we demonstrated the feasibility of pyroptosis in the clinical treatment of KIRC and provided novel ideas and suggestions for the clinical treatment of KIRC.</p

Table_4_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.xlsx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

Table_3_The role and therapeutic significance of the anoikis pathway in renal clear cell carcinoma.xlsx

Anoikis is a specialized mode of programmed cell death. Specifically, once cells detach from the original extracellular matrix, an apoptotic program is initiated, preventing colonization of the cells in distant parts of the organ. Therefore, both distant metastasis and colonization of cancer cells rely on the anoikis resistance of cancer cells. Bioinformatics analysis was performed to confirm the relation of anoikis to kidney renal cell carcinoma (KIRC). To construct a prognostic model for patients with KIRC, we investigated several genes of the anoikis pathway most closely related to KIRC and also contrasted the effects of common anticancer drugs on the KIRC pathway. Besides KIRC, we explored the expression of anoikis-related genes in various other cancers. We classified patients with KIRC into three clusters based on the coefficients and mRNA expression levels of anoikis-related genes selected using the GSVA algorithm. We used the GDSC database to predict the response of the anoikis pathway to common anticancer drugs and explored the potential targets of the anoikis pathway in KIRC. We then analyzed the response of common immunotherapies to the anoikis pathway to analyze the correlation between anoikis and immune checkpoint inhibitor therapy. Finally, eleven cancer-related genes were screened and a prognostic model was constructed using LASSO regression.</p

Table5_Potential Application of Pyroptosis in Kidney Renal Clear Cell Carcinoma Immunotherapy and Targeted Therapy.XLSX

Renal cell carcinoma (RCC) is a type of cancer with an increasing rate of morbidity and mortality and is a serious threat to human health. The treatment of RCC, especially kidney renal clear cell carcinoma (KIRC), has always been the focus of clinical treatment. Using The Cancer Genome Atlas (TCGA) database as a starting point, we explored the feasibility of applying the pyroptosis mechanism to KIRC treatment by searching for cancer markers associated with pyroptosis and cancer treatment signatures. The obtained samples were clustered using unsupervised clustering analysis to define the different KIRC subtypes with different pyroptosis expression levels. Based on this, a gene expression analysis was performed to explore the carcinogenic mechanism that is markedly related to pyroptosis. The Genomics of Drug Sensitivity in Cancer database and single sample gene set enrichment analysis (ssGSEA) algorithm were used to analyze the different treatment methods of the current prominent KIRC to determine whether pyroptosis plays a role. Finally, LASSO regression was used to screen for related genes and construct a model to predict patient prognosis. The expression levels of GSDME, CASP3, CASP4, CASP5, CHMP3, and CHMP4C were incorporated into the model construction. After verification, the prediction accuracy of the 3-, 5-, 7- and 10 years survival rates of our prognostic model were 0.66, 0.701, 0.719, and 0.728, respectively. Through the above analysis, we demonstrated the feasibility of pyroptosis in the clinical treatment of KIRC and provided novel ideas and suggestions for the clinical treatment of KIRC.</p