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
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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.
KeywordsQuantum dot Triple-negative breast cancer Epidermal growth factor receptor Collagen IV Prognosis
This work was supported by the grants from the National Science Foundation of China [grant numbers 81201196, 81471781, 81302314, and 81230031], the National Key Scientific Instrument and Equipment Development Project [grant number 20133655893], the Key Scientific Research Project of Hubei Provincial Department of Education [grant number D20126102], the Natural Science Foundation of Hubei Province, China [grant numbers 301130851 and 2011CBD489], the Research Foundation of Public Health Bureau of Hubei Province [grant numbers JS-2011018, JX4B19, and JX3A14], the Key Project of Health and the Family Planning Commission of Hubei Province [grant number WJ2015MA016].
Conflicts of interest
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