title: Quantum dot-based in situ simultaneous molecular imaging and quantitative analysis of EGFR and collagen IV and identification of their prognostic value in triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with high heterogeneity and poor prognosis. Currently, the treatment effect of TNBC has reached a bottleneck, rendering new breakthroughs difficult. Cancer invasion is not an entirely cell-autonomous process, requiring the cells to transmigrate across the surrounding extracellular matrix (ECM) barriers. Developing a new system that integrates key constituents in the tumor microenvironment with pivotal cancer cell molecules is essential for the in-depth investigation of the mechanism of invasion in TNBC. We describe a computer-aided algorithm developed using quantum dot (QD)-based multiplex molecular imaging of TNBC tissues. We performed in situ simultaneous imaging and quantitative detection of epidermal growth factor receptor (EGFR), expressed in the TNBC cell membrane, and collagen IV, the major ECM constituent; calculated the EGFR/collagen IV ratio; and investigated the prognostic value of the EGFR/collagen IV ratio in TNBC. We simultaneously imaged and quantitatively detected EGFR and collagen IV in the TNBC samples. In all patients, quantitative determination showed a statistically significant negative correlation between EGFR and collagen IV. The 5-year disease-free survival (5-DFS) of the high and low EGFR/collagen IV ratio subgroups was significantly different. The EGFR/collagen IV ratio was predictive and was an independent prognostic indicator in TNBC. Compared with EGFR expression, the EGFR/collagen IV ratio had a greater prognostic value for 5-DFS. Our findings open up a new avenue for predicting the clinical outcome in TNBC from the perspective of integrating molecules expressed in both cancer cells and the ECM.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Tower 238 Jiefang Road, Wuchang District, Wuhan, Hubei Province, 430060, People's Republic of China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zheng
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Tower 238 Jiefang Road, Wuchang District, Wuhan, Hubei Province, 430060, People's Republic of China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, Hubei, People's Republic of China.
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Head and Neck Surgery, Hubei Cancer Hospital, Wuhan, Hubei, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Tower 238 Jiefang Road, Wuchang District, Wuhan, Hubei Province, 430060, People's Republic of China.
authors.forename: Jin-Zhong
authors.initials: JZ
authors.lastname: Sun
authors.affiliation: Department of Pathology, Hubei Cancer Hospital, Wuhan, Hubei, People's Republic of China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Tower 238 Jiefang Road, Wuchang District, Wuhan, Hubei Province, 430060, People's Republic of China. sun13712@163.com.
authors.forename: Sheng-Rong
authors.initials: SR
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D011379:Prognosis; D045663:Quantum Dots / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D024141:Collagen Type IV; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Collagen IV; Epidermal growth factor receptor; Prognosis; Quantum dot; Triple-negative breast cancer