Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma

Abstract

BackgroundOne of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration.MethodsWe retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing.ResultsGenomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells.ConclusionsIn this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.

Silencing of lncRNA UCA1 Reverses Doxorubicin Resistance of Breast Cancer Through Inhibiting PI3K/AKT/mTOR Signaling Pathway

“…A previous study about UCA1 related to drug resistance reported the upregulation of UCA1 expression could be associated with the development of tamoxifen resistance in BC cells via mTOR signaling pathway [35] . Additionally, there are different studies in the literature that UCA1 increases carcinogenesis including drug resistance, and regulates the PI3K/AKT signaling pathway by targeting EZH2, PTEN molecules in the cell [36–39] . According to the results, UCA1 may play a role in doxorubicin resistance of BC lines by activating PI3K/AKT/PTEN pathway.…”

“…[35] Additionally, there are different studies in the literature that UCA1 increases carcinogenesis including drug resistance, and regulates the PI3K/AKT signaling pathway by targeting EZH2, PTEN molecules in the cell. [36][37][38][39] According to the results, UCA1 may play a role in doxorubicin resistance of BC lines by activating PI3K/AKT/PTEN pathway. It could be concluded that UCA1 may have a role in reversing doxorubicin resistance.…”