The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence

BackgroundTransmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understandin...

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Main Authors: Chen Ye, Siqian Ren, Abuduhaibaier Sadula, Xin Guo, Meng Yuan, Meng Meng, Gang Li, Xiaowei Zhang, Chunhui Yuan
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1047377/full
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author Chen Ye
Chen Ye
Siqian Ren
Abuduhaibaier Sadula
Xin Guo
Meng Yuan
Meng Meng
Gang Li
Xiaowei Zhang
Chunhui Yuan
author_facet Chen Ye
Chen Ye
Siqian Ren
Abuduhaibaier Sadula
Xin Guo
Meng Yuan
Meng Meng
Gang Li
Xiaowei Zhang
Chunhui Yuan
author_sort Chen Ye
collection DOAJ
description BackgroundTransmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understanding of this poorly characterized protein genes in PDAC.MethodsWe selected the TMEM family genes through the Human Protein Atlas and characterized their expression by single-cell and bulk transcriptomic datasets. Identification of the key TMEM genes was performed through three machine learning algorithms: LASSO, SVM-RFE and RF-SRC. Then, we established TMEM gene riskscore and estimate its implication in predicting survival and response to systematic therapy. Additionally, we explored the difference and impact of TMEM gene expression in PDAC through immunohistochemistry and cell line research.Results5 key TMEM genes (ANO1, TMEM59, TMEM204, TMEM205, TMEM92) were selected based on the single-cell analysis and machine learning survival outcomes. Patients stratified into the high and low-risk groups based on TMEM riskscore, were observed with distinct overall survival in internal and external datasets. Moreover, through bulk RNA-sequence and immunohistochemical staining we verified the protein expression of TMEM genes in PDAC and revealed TMEM92 as an essential regulator of pancreatic cancer cell proliferation, migration, and invasion.ConclusionOur study on TMEM gene expression and behavior in PDAC has revealed unique characteristics, offering potential for precise therapeutic approaches. Insights into molecular mechanisms expand understanding of PDAC complexity and TMEM gene roles. Such knowledge may inform targeted therapy development, benefiting patients.
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spelling doaj.art-4e6675d0920c4470844159755e3f890b2023-05-17T05:34:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.10473771047377The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequenceChen Ye0Chen Ye1Siqian Ren2Abuduhaibaier Sadula3Xin Guo4Meng Yuan5Meng Meng6Gang Li7Xiaowei Zhang8Chunhui Yuan9Department of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of Hepatobiliary surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaDepartment of Hematology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of General Surgery, Peking University Third Hospital, Beijing, ChinaBackgroundTransmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understanding of this poorly characterized protein genes in PDAC.MethodsWe selected the TMEM family genes through the Human Protein Atlas and characterized their expression by single-cell and bulk transcriptomic datasets. Identification of the key TMEM genes was performed through three machine learning algorithms: LASSO, SVM-RFE and RF-SRC. Then, we established TMEM gene riskscore and estimate its implication in predicting survival and response to systematic therapy. Additionally, we explored the difference and impact of TMEM gene expression in PDAC through immunohistochemistry and cell line research.Results5 key TMEM genes (ANO1, TMEM59, TMEM204, TMEM205, TMEM92) were selected based on the single-cell analysis and machine learning survival outcomes. Patients stratified into the high and low-risk groups based on TMEM riskscore, were observed with distinct overall survival in internal and external datasets. Moreover, through bulk RNA-sequence and immunohistochemical staining we verified the protein expression of TMEM genes in PDAC and revealed TMEM92 as an essential regulator of pancreatic cancer cell proliferation, migration, and invasion.ConclusionOur study on TMEM gene expression and behavior in PDAC has revealed unique characteristics, offering potential for precise therapeutic approaches. Insights into molecular mechanisms expand understanding of PDAC complexity and TMEM gene roles. Such knowledge may inform targeted therapy development, benefiting patients.https://www.frontiersin.org/articles/10.3389/fonc.2023.1047377/fulltransmembrane protein genepancreatic ductal adenocarcinomatumor microenvironmentsingle-cell RNA sequenceprognostic marker
spellingShingle Chen Ye
Chen Ye
Siqian Ren
Abuduhaibaier Sadula
Xin Guo
Meng Yuan
Meng Meng
Gang Li
Xiaowei Zhang
Chunhui Yuan
The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
Frontiers in Oncology
transmembrane protein gene
pancreatic ductal adenocarcinoma
tumor microenvironment
single-cell RNA sequence
prognostic marker
title The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
title_full The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
title_fullStr The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
title_full_unstemmed The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
title_short The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence
title_sort expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single cell rna sequence
topic transmembrane protein gene
pancreatic ductal adenocarcinoma
tumor microenvironment
single-cell RNA sequence
prognostic marker
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1047377/full
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