Gene signatures in patients with early breast cancer and relapse despite pathologic complete response

Abstract

A substantial minority of early breast cancer (EBC) patients relapse despite their tumors achieving pathologic complete response (pCR) after neoadjuvant therapy. We compared gene expression (BC360; nCounter® platform; NanoString) between primary tumors of patients with post-pCR relapse (N = 14) with: (i) matched recurrent tumors from same patient (intraindividual analysis); and (ii) primary tumors from matched controls with pCR and no relapse (N = 41; interindividual analysis). Intraindividual analysis showed lower estrogen receptor signaling signature expression in recurrent tumors versus primaries (logFC = −0.595; P = 0.022). Recurrent tumors in patients with distant metastases also exhibited reduced expression of immune-related expression parameters. In interindividual analyses, primary tumor major histocompatibility complex class II expression was lower versus controls in patients with any relapse (logFC = −0.819; P = 0.030) or distant relapse (logFC = −1.151; P = 0.013). Primaries with later distant relapse also had greater homologous recombination deficiency than controls (logFC = 0.649; P = 0.026). Although no associations remained statistically significant following adjustment for false discovery rate, our results show that transcriptomic analyses have potential for prognostic value and may help in selecting optimal treatment regimens for EBC at risk of relapse and warrant further investigation.

End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO

“…Specifically, miR-194-5p is contained in the exosomes of dying cells and is released to residual ALDH-positive tumor-repopulating cells for their recovery. This finding is consistent with the enrichment of cells with stemness phenotype in occult metastatic lesion (47), and the overexpression of stemness signatures in triple negative breast cancer primary tumor of patients who eventually relapse regardless a pCR (10).…”

“…However, a reliable tool to separate patients at risk of relapse from those already cured after neoadjuvant therapy is currently lacking, hindering appropriate selection of adjuvant therapy escalation candidates. Primary tumor gene expression, proteomics and mutational profiling represent promising biomarkers, but need repeated tissue sampling and high-profile technology which limit their use in daily practice ( 10 , 11 ). A possible alternative is offered by the development of a non-invasive procedure such as liquid biopsy.…”

Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis

“…The false discovery rate (FDR) correction method was applied to the p -values in the differential expression analysis. Here, log2FC > 0 was considered an upregulated gene, as described previously, while log2FC < 0 was considered a downregulated gene [ 36 , 37 ]. All experiments were repeated three times or more, and all statistical and visualization work was carried out using GraphPad Prism 9.0 and SPSS software.…”

Prognostic value of the ferroptosis-related gene SLC2A3 in gastric cancer and related immune mechanisms

“…When the value of |logFC| was 1, 1.5, or 2, the GEO dataset would obtain very few DEGs because the threshold was too high. In order to keep the threshold consistent, we took |logFC| > 0.5 both in the TCGA and GEO datasets ( Huang et al, 2021 ; Bruzas et al, 2022 ). The volcano map and heat map of DEGs were drawn using the “ggplot2” R package to visualize the differential expression of DEGs.…”