TY - JOUR
T1 - Transcriptomic properties of her2+ ductal carcinoma in situ of the breast associate with absence of immune cells
AU - Agahozo, Marie Colombe
AU - Smid, Marcel
AU - van Marion, Ronald
AU - Hammerl, Dora
AU - van den Bosch, Thierry P.P.
AU - Timmermans, Mieke A.M.
AU - Heijerman, Chayenne J.
AU - Westenend, Pieter J.
AU - Debets, Reno
AU - Martens, John W.M.
AU - van Deurzen, Carolien H.M.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/12
Y1 - 2021/8/12
N2 - The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor‐infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL‐poor HER2+ DCIS to that of TIL‐rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL‐poor DCIS cases were micro‐dissected for RNA isolation. The Ion AmpliSeq Tran-scriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann–Whitney rank sum test was used to analyze differentially expressed genes between TIL‐poor and TIL‐rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein ex-pression. We identified a 29‐gene expression profile that differentiated TIL‐rich from TIL‐poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously de-scribed in breast cancer and cancer immunity and were more highly expressed in TIL‐rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL‐rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune‐mediated therapy in HER2+ DCIS, such as targeted vaccine therapy.
AB - The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor‐infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL‐poor HER2+ DCIS to that of TIL‐rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL‐poor DCIS cases were micro‐dissected for RNA isolation. The Ion AmpliSeq Tran-scriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann–Whitney rank sum test was used to analyze differentially expressed genes between TIL‐poor and TIL‐rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein ex-pression. We identified a 29‐gene expression profile that differentiated TIL‐rich from TIL‐poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously de-scribed in breast cancer and cancer immunity and were more highly expressed in TIL‐rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL‐rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune‐mediated therapy in HER2+ DCIS, such as targeted vaccine therapy.
UR - http://www.scopus.com/inward/record.url?scp=85113237876&partnerID=8YFLogxK
U2 - 10.3390/biology10080768
DO - 10.3390/biology10080768
M3 - Article
C2 - 34440000
AN - SCOPUS:85113237876
SN - 2079-7737
VL - 10
JO - Biology
JF - Biology
IS - 8
M1 - 768
ER -
