Relationship of PI3K-Akt/mTOR/AMPK signaling pathway genetic mutation with efficacy and prognosis in nasopharyngeal carcinoma.

objectivesGenetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.

methodsA total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time.

resultsThe 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ

conclusionsThe NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.