3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways

Background: Extensive amounts of archived formalin fixed paraffin embedded (FFPE) human tumor tissues are the ultimate resource to investigate signaling network underlying tumorigenesis in human. Yet, their usage is severely limited for lacking of suitable protein techniques. In this study, a quanti...

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Main Authors: Jiahong Lyu MS, Guohua Yu MD, PhD, Yunyun Zhang MS, Yan Lyu MS, Wenfeng Zhang MS, Jiandi Zhang PhD, Fangrong Tang MS
Format: Article
Language:English
Published: SAGE Publishing 2021-12-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/15330338211065603
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author Jiahong Lyu MS
Guohua Yu MD, PhD
Yunyun Zhang MS
Yan Lyu MS
Wenfeng Zhang MS
Jiandi Zhang PhD
Fangrong Tang MS
author_facet Jiahong Lyu MS
Guohua Yu MD, PhD
Yunyun Zhang MS
Yan Lyu MS
Wenfeng Zhang MS
Jiandi Zhang PhD
Fangrong Tang MS
author_sort Jiahong Lyu MS
collection DOAJ
description Background: Extensive amounts of archived formalin fixed paraffin embedded (FFPE) human tumor tissues are the ultimate resource to investigate signaling network underlying tumorigenesis in human. Yet, their usage is severely limited for lacking of suitable protein techniques. In this study, a quantitative, objective, absolute, and high throughput immunoblot method, quantitative dot blot (QDB), was explored to address this issue by investigating the putative relationship between estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) pathways in breast cancer tumorigenesis. Methods: In this descriptive observational retrospective study, ER, PR, Her2, and Ki67 protein levels were measured absolutely and quantitatively in 852 FFPE breast cancer tissues using the QDB method. ER, PR, and Her2 levels were charted on the X, Y, and Z-axes to observe samples distribution in a 3D scatterplot. Results: A “seesaw” relationship between ER/PR and Her2 pathways was observed in ER–PR–Her2 space, characterized by the expression levels of these 3 proteins. Specimens with strong expressions of ER/PR proteins were found spreading along the ER/PR floor while those with strong Her2 expression were found wrapping around the Her2 axis. Those lacking strong expressions of all 3 proteins were found accumulating at the intersection of the ER, PR, and Her2 axes. Few specimens floated in the ER–PR–Her2 space to suggest the lack of co-expression of all 3 proteins simultaneously. Ki67 levels were found to be significantly reduced in specimens spreading in the ER–PR space. Conclusions: The unique distribution of specimens in ER–PR–Her2 space prior to any clinical intervention provided visual support of bidirectional talk between ER/PR and Her2 pathways in breast cancer specimens. Clinical interventions to suppress these 2 pathways alternatively warrant further exploration for breast cancer patients accordingly. Our study also demonstrated that the QDB method is an effective tool to analyze archived FFPE cancer specimens in biomedical research.
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spelling doaj.art-7b1d263800fc4a919ea677afa98fca6a2022-12-22T02:05:27ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382021-12-012010.1177/153303382110656033D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 PathwaysJiahong Lyu MS0Guohua Yu MD, PhD1Yunyun Zhang MS2Yan Lyu MS3Wenfeng Zhang MS4Jiandi Zhang PhD5Fangrong Tang MS6 Yantai Quanticision Diagnostics, Inc, Yantai, P. R. China Yuhuangding Hospital, affiliated Qingdao University, Yantai, P. R. China Yantai Quanticision Diagnostics, Inc, Yantai, P. R. China Yantai Quanticision Diagnostics, Inc, Yantai, P. R. China Yantai Quanticision Diagnostics, Inc, Yantai, P. R. China Yantai Quanticision Diagnostics, Inc, Yantai, P. R. China Yantai Quanticision Diagnostics, Inc, Yantai, P. R. ChinaBackground: Extensive amounts of archived formalin fixed paraffin embedded (FFPE) human tumor tissues are the ultimate resource to investigate signaling network underlying tumorigenesis in human. Yet, their usage is severely limited for lacking of suitable protein techniques. In this study, a quantitative, objective, absolute, and high throughput immunoblot method, quantitative dot blot (QDB), was explored to address this issue by investigating the putative relationship between estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) pathways in breast cancer tumorigenesis. Methods: In this descriptive observational retrospective study, ER, PR, Her2, and Ki67 protein levels were measured absolutely and quantitatively in 852 FFPE breast cancer tissues using the QDB method. ER, PR, and Her2 levels were charted on the X, Y, and Z-axes to observe samples distribution in a 3D scatterplot. Results: A “seesaw” relationship between ER/PR and Her2 pathways was observed in ER–PR–Her2 space, characterized by the expression levels of these 3 proteins. Specimens with strong expressions of ER/PR proteins were found spreading along the ER/PR floor while those with strong Her2 expression were found wrapping around the Her2 axis. Those lacking strong expressions of all 3 proteins were found accumulating at the intersection of the ER, PR, and Her2 axes. Few specimens floated in the ER–PR–Her2 space to suggest the lack of co-expression of all 3 proteins simultaneously. Ki67 levels were found to be significantly reduced in specimens spreading in the ER–PR space. Conclusions: The unique distribution of specimens in ER–PR–Her2 space prior to any clinical intervention provided visual support of bidirectional talk between ER/PR and Her2 pathways in breast cancer specimens. Clinical interventions to suppress these 2 pathways alternatively warrant further exploration for breast cancer patients accordingly. Our study also demonstrated that the QDB method is an effective tool to analyze archived FFPE cancer specimens in biomedical research.https://doi.org/10.1177/15330338211065603
spellingShingle Jiahong Lyu MS
Guohua Yu MD, PhD
Yunyun Zhang MS
Yan Lyu MS
Wenfeng Zhang MS
Jiandi Zhang PhD
Fangrong Tang MS
3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
Technology in Cancer Research & Treatment
title 3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
title_full 3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
title_fullStr 3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
title_full_unstemmed 3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
title_short 3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways
title_sort 3d visualization of the dynamic bidirectional talk between er pr and her2 pathways
url https://doi.org/10.1177/15330338211065603
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