The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients

Enrico Berrino; Umberto Miglio; Sara Erika Bellomo; Carla Debernardi; Alberto Bragoni; Annalisa Petrelli; Eliano Cascardi; Silvia Giordano; Filippo Montemurro; Caterina Marchiò; Tiziana Venesio; Anna Sapino

doi:10.3390/cells11121944

The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients

Cells. 2022 Jun 16;11(12):1944. doi: 10.3390/cells11121944.

Authors

Enrico Berrino^{1

2}, Umberto Miglio¹, Sara Erika Bellomo^{1

3}, Carla Debernardi², Alberto Bragoni^{1

2}, Annalisa Petrelli¹, Eliano Cascardi^{1

2}, Silvia Giordano^{1

3}, Filippo Montemurro¹, Caterina Marchiò^{1

2}, Tiziana Venesio¹, Anna Sapino^{1

2}

Affiliations

¹ Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
² Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
³ Department of Oncology, University of Turin, 10124 Turin, Italy.

Abstract

Background: Long-Interspersed Nuclear Element (L1) retrotransposons are silenced in healthy tissues but unrepressed in cancer. Even if L1 reactivation has been associated with reduced overall survival in breast cancer (BC) patients, a comprehensive correlation with clinicopathological features is still missing.

Methods: Using quantitative, reverse-transcription PCR, we assessed L1 mRNA expression in 12 BC cells, 210 BC patients and in 47 normal mammary tissues. L1 expression was then correlated with molecular and clinicopathological data.

Results: We identified a tumor-exclusive expression of L1s, absent in normal mammary cells and tissues. A positive correlation between L1 expression and tumor dedifferentiation, lymph-node involvement and increased immune infiltration was detected. Molecular subtyping highlighted an enrichment of L1s in basal-like cells and cancers. By exploring disease-free survival, we identified L1 overexpression as an independent biomarker for patients with a high risk of recurrence in hormone-receptor-negative BCs.

Conclusions: Overall, L1 reactivation identified BCs with aggressive features and patients with a worse clinical fate.

Keywords: L1 retrotransposons; basal-like; breast cancer; tumor-exclusive biomarker.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen / metabolism
Hormones
Humans
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / pathology
Retroelements*
Triple Negative Breast Neoplasms* / pathology

Substances

B7-H1 Antigen
Hormones
Retroelements

Grants and funding

This research was funded by the Project SEE-HER funded under FPRC 5X1000 MS2017 PTCRC. Part of the analyses were supported by Dipartimenti di Eccellenza 2018–2022 (Project No. D15D18000410001) and by FONDAZIONE AIRC under IG 2019—ID. 22850 project—P.I. Marchiò Caterina. E.B. was the recipient of a Ph.D. fellowship under the funding of Dipartimenti di Eccellenza 2018–2022 (Project No. 521 D15D18000410001).