Transcriptomic analysis of breast cancer patients sensitive and resistant to chemotherapy: Looking for overall survival and drug resistance biomarkers 

Abstract

Neoadjuvant chemotherapy is one important therapeutic strategy for breast cancer with the drawback of resistance development. Chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to discover differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who received neoadjuvant chemotherapy were enrolled in this study and according to their pathological response were assigned as sensitive or resistant. To evaluate DEGs, GO, KEGG, and protein-protein interactions, RNAseq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study. Seven of those DEGs correlated with overall survival, of them the sub-expression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN and the over expression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.

Upregulated keratin 15 links to the occurrence of lymphovascular invasion, stromal cervical invasion as well as unfavorable survival profile in endometrial cancer patients

“…[12] Besides, another study reveals that KRT15 overexpression is associated with tumor metastasis in breast cancer patients. [17] In the present study, KRT15 protein expression was correlated with the occurrence of lymphovascular invasion and more advanced FIGO stage; meanwhile, KRT15 mRNA expression was correlated with the more advanced FIGO stage and marginally associated with the occurrence of stromal cervical invasion. Possible explanations could be that: KRT15 upregulation is associated with enhanced cancer stem cell property which exhibits a strong infiltration capacity; thus, KRT15 overexpression is linked with the occurrence of lymphovascular invasion and stromal cervical invasion in EC patients.…”

“…[23,24] Apart from the above-mentioned relevance of KRT15 with clinical features, its upregulation also links with an unsatisfying survival profile in breast cancer and non-small cell lung cancer. [17,25] Herein, the KRT15 overexpression was marginally correlated with accumulating DFS and OS in EC patients, which was estimated by Kaplan-Meier method and analyzed by log-rank test, whereas further adjusted multivariate Cox's regressions showed that tumor KRT15 protein (high vs low) was independently correlated with poor DFS and OS. Possible explanations could be that KRT15 overexpression is linked with enhanced cancer stem cell properties and therefore lined with a higher recurrence rate; thus, KRT15 overexpression is correlated with poor survival indexes.…”

“…[12] Differently, it is illustrated that KRT15 is downregulated in carcinoma tissue compared with normal tissue from breast cancer patients. [14,15,17] KRT15 expression discloses an opposite trend in breast cancer, which might be explained by that: The apoptosis and differentiation of KRT15 would be influenced by endocrine status, hence, we hypothesize that KRT15 expression in breast cancer might be affected by the hormonal environment (such as estrogen, progesterone, etc) [18,19] ; whereas, this speculation needs further investigation in the in vivo and in vitro studies. In the current study, it was discovered that KRT15 was higher in tumor tissue compared with adjacent tissue; meanwhile, it exhibited an acceptable capability in distinguishing tumor tissue from adjacent tissue.…”

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival

“…In addition, low expression of this gene was associated with a worse prognosis for OS. This gene has already been reported to predict treatment response and OS (Sinn et al, 2021;Barron-Gallardo et al, 2022). ATF6B has two ensemble IDs (ENSG00000228628 and ENSG00000213676).…”

“…A previous study was conducted to determine biomarkers of response to neoadjuvant chemotherapy in patients with breast cancer (GSE162187) (Barron-Gallardo et al, 2022). In this study, HER2+ samples were taken and included in the RNA-seq analysis; five samples were from patients categorized as resistant to treatment, and three samples were from patients sensitive to treatment.…”