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ERCC2, KDM6A, and TERT as Key Prognostic Factors in Bladder Cancer: Insights from the AACR Project GENIE Database
Background
Urothelial carcinoma (UC) is among the top 10 frequently diagnosed cancers in the world. Mutations in FGFR3, ARID1A, and TP53 are well documented as being some of the most frequent mutations found in UC. Despite advances in treatment, survival outcomes remain poor, especially in advanced stages. To promote future pharmacotherapeutic development, the molecular understanding of UC needs to be continually updated using more recently available databases.
Methods
This study utilizes the AACR Project GENIE database from the American Association for Cancer Research to explore the mutational profiles of patients with UC. Gene mutation frequencies were calculated, and two Kaplan-Meier curves were drawn for each gene, showing one curve for patients with the mutation and one for those without. Log-Rank tests were calculated with subsequent FDR (Benjamini–Hochberg) correction applied to account for multiple hypothesis testing. Data was analyzed using R 4.4.2 and statistical significance was set at α = 0.05.
Results
In this study, 4525 patients had histology consistent with UC. The 5 most common mutations were TERT (n = 1714, 37.9%), TP53 (n = 1689, 37.3%), KDM6A (n = 1091, 24.1%), ARID1A (n = 872, 19.3%), and FGFR3 (n = 762, 16.8%). Mutations associated with differential survival outcomes included ERCC2 (mutated n = 387, wild type n = 3751, p < 0.0001), KDM6A (mutated n = 1091, wild type n = 3047, p < 0.0001), TERT (mutated n = 1714, wild type n = 2424), and TP53 (mutated n = 1689, wild type n = 2449, p < 0.0001).
Conclusions
Interestingly, while mutations in TP53 and ERCC2 were associated with shorter median survival, mutations in KDM6A and TERT were associated with longer median survival.
Background
Urothelial carcinoma (UC) is among the top 10 frequently diagnosed cancers in the world. Mutations in FGFR3, ARID1A, and TP53 are well documented as being some of the most frequent mutations found in UC. Despite advances in treatment, survival outcomes remain poor, especially in advanced stages. To promote future pharmacotherapeutic development, the molecular understanding of UC needs to be continually updated using more recently available databases.
Methods
This study utilizes the AACR Project GENIE database from the American Association for Cancer Research to explore the mutational profiles of patients with UC. Gene mutation frequencies were calculated, and two Kaplan-Meier curves were drawn for each gene, showing one curve for patients with the mutation and one for those without. Log-Rank tests were calculated with subsequent FDR (Benjamini–Hochberg) correction applied to account for multiple hypothesis testing. Data was analyzed using R 4.4.2 and statistical significance was set at α = 0.05.
Results
In this study, 4525 patients had histology consistent with UC. The 5 most common mutations were TERT (n = 1714, 37.9%), TP53 (n = 1689, 37.3%), KDM6A (n = 1091, 24.1%), ARID1A (n = 872, 19.3%), and FGFR3 (n = 762, 16.8%). Mutations associated with differential survival outcomes included ERCC2 (mutated n = 387, wild type n = 3751, p < 0.0001), KDM6A (mutated n = 1091, wild type n = 3047, p < 0.0001), TERT (mutated n = 1714, wild type n = 2424), and TP53 (mutated n = 1689, wild type n = 2449, p < 0.0001).
Conclusions
Interestingly, while mutations in TP53 and ERCC2 were associated with shorter median survival, mutations in KDM6A and TERT were associated with longer median survival.
Background
Urothelial carcinoma (UC) is among the top 10 frequently diagnosed cancers in the world. Mutations in FGFR3, ARID1A, and TP53 are well documented as being some of the most frequent mutations found in UC. Despite advances in treatment, survival outcomes remain poor, especially in advanced stages. To promote future pharmacotherapeutic development, the molecular understanding of UC needs to be continually updated using more recently available databases.
Methods
This study utilizes the AACR Project GENIE database from the American Association for Cancer Research to explore the mutational profiles of patients with UC. Gene mutation frequencies were calculated, and two Kaplan-Meier curves were drawn for each gene, showing one curve for patients with the mutation and one for those without. Log-Rank tests were calculated with subsequent FDR (Benjamini–Hochberg) correction applied to account for multiple hypothesis testing. Data was analyzed using R 4.4.2 and statistical significance was set at α = 0.05.
Results
In this study, 4525 patients had histology consistent with UC. The 5 most common mutations were TERT (n = 1714, 37.9%), TP53 (n = 1689, 37.3%), KDM6A (n = 1091, 24.1%), ARID1A (n = 872, 19.3%), and FGFR3 (n = 762, 16.8%). Mutations associated with differential survival outcomes included ERCC2 (mutated n = 387, wild type n = 3751, p < 0.0001), KDM6A (mutated n = 1091, wild type n = 3047, p < 0.0001), TERT (mutated n = 1714, wild type n = 2424), and TP53 (mutated n = 1689, wild type n = 2449, p < 0.0001).
Conclusions
Interestingly, while mutations in TP53 and ERCC2 were associated with shorter median survival, mutations in KDM6A and TERT were associated with longer median survival.
Organs of Metastasis Predominate with Age in Non-Small Cell Lung Cancer Subtypes: National Cancer Database Analysis
Background
Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.
Objective
To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).
Methods
The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.
Results
In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.
Conclusions
This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.
Background
Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.
Objective
To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).
Methods
The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.
Results
In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.
Conclusions
This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.
Background
Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.
Objective
To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).
Methods
The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.
Results
In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.
Conclusions
This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.