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Published on: April 6, 2016
Immune cell infiltration and drug sensitivity in PIK3CA-mutated esophageal squamous cell carcinoma: A TCGA database
Shuo He1, Qing Liu2, Shujuan Luo1
1State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi 830017, China.
Abstract:
Recent studies have increasingly focused on PIK3CA mutations in esophageal squamous cell carcinoma (ESCC); however, the clinicopathological significance of these mutations within the tumor microenvironment remains underexplored. This study aimed to evaluate and compare the clinicopathological significance of mutated PIK3CA in ESCC using in silico analyses of the ESCC dataset from the TCGA database. We assessed prognosis, differential expression, correlation with immune cell infiltration and immune checkpoint expression, heterogeneity, and drug sensitivity in comparison with wild-type PIK3CA. Our findings revealed that PIK3CA mutation is associated with increased tumor mutation burden and significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells. Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC.
Insights
PIK3CA mutations in esophageal squamous cell carcinoma (ESCC) correlate with increased tumor mutation burden and specific immune cell infiltration. Mutated PIK3CA in ESCC may confer resistance to p38/JNK MAPK inhibitors.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- PIK3CA mutations are increasingly studied in esophageal squamous cell carcinoma (ESCC).
- The clinicopathological significance of PIK3CA mutations within the tumor microenvironment of ESCC is not well understood.
Purpose of the Study:
- To evaluate the clinicopathological significance of PIK3CA mutations in ESCC.
- To compare mutated PIK3CA with wild-type PIK3CA regarding prognosis, immune infiltration, and drug sensitivity using in silico analyses.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for ESCC dataset analysis.
- Performed in silico analyses to assess prognosis, differential gene expression, immune cell infiltration, immune checkpoint expression, tumor heterogeneity, and drug sensitivity.
Main Results:
- PIK3CA mutation was associated with increased tumor mutation burden.
- PIK3CA mutation significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells.
- ESCC cells with PIK3CA mutations showed reduced sensitivity to p38/JNK MAPK inhibitors compared to wild-type.
Conclusions:
- Mutational PIK3CA influences the tumor microenvironment in ESCC, particularly immune cell infiltration.
- PIK3CA mutations in ESCC may contribute to resistance against p38 and JNK MAPK targeted therapies.
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