Single gene pan cancer + simple experiment can be published 7 points+

Introduction

CD147 It plays an important role in promoting tumor proliferation and inhibiting cancer cell apoptosis in tumor microenvironment .

Background introduction

The key to the high score of single gene pan cancer lies in the selection of genes . Today, I bring you a single gene pan cancer + A simple experiment was published 7 branch + Of Front. Immunol The article , titled Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer.

Data is introduced

Pancarcinoma RNA-seq Data from TCGA get , Including having OS and DSS Complete survival information and samples of tumor histology . Including adrenocortical carcinoma （ACC）, Bladder cancer （BLCA）, Mammary cancer （BRCA）, cervical carcinoma （CESC）, Cholangiocarcinoma （CHOL）, colorectal cancer （COAD）, esophageal cancer （ESCA）, Glioblastoma （GBM）, Squamous cell carcinoma of head and neck （HNSC）, Chromophobe cell carcinoma of kidney （KICH）, Renal clear cell carcinoma （ KIRC ）, Papillary cell carcinoma of the kidney （KIRP）, Low grade glioma （LGG）, Hepatocellular carcinoma （LIHC）, Adenocarcinoma of the lung （LUAD）, Squamous cell carcinoma of lung （LUSC）, Mesothelioma （MESO）, oophoroma （OV）, Pancreatic adenocarcinoma （PAAD）, Pheochromocytoma and paraganglioma （PCPG）, prostatic cancer （PRAD）, Rectal cancer （READ）, Sarcoma （SARC）, Melanoma of skin （SKCM）, Gastric adenocarcinoma （STAD）, Testicular cancer （TGCT）, Thyroid cancer （THCA）, Thymoma （THYM）, Endometrial carcinoma （UCEC）, Uterine sarcoma （UCS） And eye melanoma （UVM）. Cell line data from CCLE And the human protein map （HPA） download . Single cell data from GEO And the single cell portal platform （http://singlecell.broadinstitute.org） download .

Result analysis

01

CD147 Expression and mutation of

The research design is shown in the figure 1 Shown .

chart 1

First , The author observed 31 individual GTEx Of normal tissue CD147 Expression level （ chart 2A）.CD147 The first three tissues that are enriched are the testes 、 Heart and colon . come from CCLE The data shows that ,CD147 stay 38 Highly expressed in tumor cell lines , Especially in glioma 、 Medulloblastoma 、 Melanoma 、 Endometrium and thyroid （ chart 2B）. come from HPA The data shows that , The first five are rich in CD147 RNA Our cell line is U-87、U-2197、NTERA-2、HaCaT and MCF7（ chart 2C）. come from TCGA The data shows that , except KIRC、LAML、READ、UCS、SARC outside , Of almost all cancer samples CD147 The expression was significantly higher than that of normal control （ chart 2D）.

chart 2

Author use cBioportal Data observed in Pan cancer CD147 The mutation of . It turns out that ,SARC、CESC、LGG and OV With high mutation level , Change frequency more than 4%. The author also analyzes CD147 mRNA The relationship between level and mutation type and copy number change . Total findings 64 Mutation sites （ Include 52 Missense 、8 A truncation 、3 Splices and 1 Fusion ）.

02

CD147 Prognosis of

The author passes KM The curve analyses CD147 Prognostic value in Pan cancer .CD147 In predicting many tumor types OS and DSS Show significant value in .CD147 High expression and BRCA、CHOL、COAD、HNSC、LGG、LIHC、LUAD、SARC and SKCM Of OS Short related to （ chart 3C）. contrary , stay ACC、KICH、KIRC、KIRP、UCEC in ,CD147 High expression and longer OS relevant （ chart 3C）. Besides , Over expressed CD147 And BRCA、HNSC、LGG、LIHC、LUAD、READ、SARC、SKCM and THCA Medium DSS Reduce the relevant , And with the ACC、 Lymphoid tumors are diffuse and large B Cell lymphoma (DLBC)、KIRC、KIRP、UCEC Medium DSS Extend about .

chart 3

03

CD147 Immune infiltration

In order to identify generalized cancer TME in CD147 Immune status , Author use ESTIMATE The algorithm calculates CD147 Level and immune score 、 Estimate the correlation between scores and matrix scores .CD147 The top three tumors significantly correlated with interstitial score were TGCT、THCA and KIRC.CD147 The top three tumors significantly correlated with immune score were THCA、SKCM and KIRC.CD147 The first three tumors with a significant correlation with estimated scores were KIRC、THCA and SKCM.

CD147 In terms of immune infiltration ,BRCA、KIRC and LIHC Is the first three most prominent types of cancer . Besides , Raised CD147 Level and GBM、READ and STAD There was a significant correlation between the number of new antigens in .

chart 4

In order to elucidate pan cancer TME CD147 And immune cells , Six algorithms are used to quantify immune cells , Include TIMER（ chart 4A）、EPIC（ chart 4B）、quantTIseq（ chart 4C）、MCP -counter（ chart 4D）、CIBERSORT and xCell. It turns out that ,CD147 It has a close relationship with immune cells in Pan cancer , Especially in BRCA、KIRC、KIRP、PRAD and SKCM in ,CD147 High expression and CD4+ T cells 、CD8+ T cells 、 Neutrophils 、B There is a significant positive correlation between macrophages and cells （ chart 4A、B、D）. CD147 High expression and BLCA、BRCA、COAD、GBM、KIRC、PRAD、LIHC、PRAD、LUAD、STAD and SKCM Medium M1 or M2 Macrophages are significantly correlated （ chart 4C）.

chart 5

The author found CD147 And COAD、DLBC、ESCA、HNSC、KIRC、KIRP、LIHC、LUSC、SKCM and STAD Microsatellite instability in （MSI） There is a positive correlation , And with the TGCT Medium MSI There is a negative correlation （ chart 5A).CD147 And COAD、ESCA、GBM、KIRP、LGG、PAAD、STAD、THYM and UCEC Tumor mutation load in (TMB) There is a positive correlation , And with the LAML Medium TMB There is a negative correlation （ chart 5B ）.

Last , The author discusses CD147 The relationship between expression and classical immune checkpoints , for example SIGLEC15、TIGIT、CD274、HAVCR2、PDCD1、CTLA4、LAG3 and PDCD1LG2（ chart 5C）. All in all ,CD147 It plays an important role in the immune infiltration of Pan cancer , It may become a new target of immunotherapy in tumor therapy .

04

CD147 The function of

according to GSVA Calculated GO enrichment ,CD147 It is negatively correlated with immune related pathways in various cancers , Especially in BRCA、GBM、KIRC、KIRP、PRAD、SKCM and THCA in （ chart 6A）. Most of these pathways are involved in fibroblasts 、T Activation and proliferation of cellular and macrophage related pathways . meanwhile , The first three negative enrichment pathways are Alzheimer's disease 、 Huntington's disease 、 Parkinson's disease 、 Glutathione metabolism and pyruvate metabolism （ chart 6B）, The first four positive enrichment pathways are based on KEGG Of ABC Transporter term （ chart 6C）. according to HALLMARK The term , Glycolysis 、MYC Target and oxidative phosphorylation are the first three negative enrichment pathways （ chart 6D）, The first four positive enrichment pathways are KRAS Signal transmission 、 Spermatogenesis 、 Bile acid metabolism and allograft rejection （ chart 6E）.

chart 6

05

Single cell analysis and immunofluorescence staining

The authors studied several types of cancer CD147 Expression in tumor and stromal cells , Include GBM（ chart 7A）、HNSC（ chart 7B）、KIRC（ chart 7C）、LUAD（ chart 7D）、PRAD（ chart 7E）、CHOL（ chart 7F） etc. . It turns out that CD147 It is highly co expressed on cancer cells and stromal cells in these cancers , Especially in M2 Macrophages 、 Macrophages 、T cells 、B Cells and CAF On .

chart 7

The authors used multiple immunofluorescence staining to verify that CD147 And macrophages (CD68) and M2 Macrophages (CD163) Co expression of , among CD68 Marked in red ,CD163 It's marked green ,CD147 Marked purple ,DAPI Is marked in blue （ chart 8）.

chart 8

06

CD147 With immunotherapy and drug prediction

Last , To explore CD147 Potential value as a new immune target for Pan cancer , The author predicts that based on CD147 Expression of immunotherapeutic responses and sensitive drugs （ chart 9）.CD147 Predictable 4 Immunotherapy responses in a murine immunotherapy cohort , These responders are more likely to have elevated CD147 level （ chart 9A）.

The author also calculated CD147 Biomarker correlation , Compare it with a standardized biomarker based on the predictive power of the immunotherapy response of the human immunotherapy cohort . The author found that only CD147 Of AUC exceed 0.5（ chart 9B）.

chart 9

be based on GDSC Data sets CD147 The correlation between levels and drug sensitivity suggests that , Methotrexate 、TPCA-1（IKK-2 Inhibitors ） and PAC-1（procaspase Activating compounds ） Is with the CD147 Expression was positively correlated with the first three drugs （ chart 9C). contrary , Bleomycin 、17-AAG With docetaxel is with CD147 The first three drugs expressed negative correlation （ chart 9C）. be based on CTRP Data sets CD147 The correlation between levels and drug sensitivity shows ,LRRK2-IN-1（LRRK2 Effective and selective inhibitors of ）、PRIMA-1（ mutation p53 Reactivators ） And his sidinalin （HDAC Inhibitors ） Is the top three drugs and CD147 Expression was positively correlated （ chart 9D）. These results prove that CD147 The value of immunotherapy in Pan cancer , A series of targeted small molecule drugs with good therapeutic effects were predicted , Targeting pan cancer CD147 The immunotherapy provided a direction .

Editor's summary

This article is a traditional single gene universal cancer article , Its highlight is the addition of immunofluorescence experiments , And the genes have chosen CD147 This is closely related to immunity CD molecular , Remind us to do single gene pan cancer gene selection , We must select the star genes that are closely related to tumor and immunity .