Dados do Resumo

Título

Assessing the Immunoscore-Based Expression Model (ISBE) for Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Introdução

Accurately predicting response to neoadjuvant chemotherapy and radiotherapy (nCRT) in rectal cancer is crucial for optimizing treatment strategies and improving patient outcomes. The Immunoscore (ISB), a predictive biomarker based on immunohistochemistry (IHC), has been increasingly implemented in clinical practice. However, ISB's reliance on IHC limits its precision and reproducibility across diverse settings. This study aims to develop a molecular version of ISB (ISBE) using transcriptomics, enhancing predictive accuracy by overcoming the limitations of histology-based approaches.

Objetivo

This study aims to develop and validate ISBE, a molecular biomarker based on transcriptomic data, to predict response to nCRT in rectal cancer, using deconvolution tools like CIBERSORTx. By the end, we assess ISBE's predictive accuracy using a public RNAseq dataset.

Métodos

We utilized publicly available RNAseq data from Chatila et al. (2022) (GSE209746) to estimate ISBE in 110 rectal cancer patients who underwent nCRT. Patients were classified into responders (nCRT-R, 35) and non-responders (nCRT-NR, 70). CIBERSORTx was used to estimate immune cell composition from the transcriptomic data using the LM22 signature, which differentiates 22 immune cell populations, including various T cell subtypes, B cells, NK cells, and myeloid cells. ISBE was calculated by grouping CD8+ T cells and CD3+ T cells, converting into percentiles, and classifying patients into Low, Intermediate, and High ISBE based on predefined cutoff groups using R software for statistical computing. Survival analysis, including overall survival (OS) and disease-free survival (DFS), was conducted using Kaplan-Meier curves, and statistical significance was determined via the log-rank test across ISBE groups and between pairs of groups.

Resultados

We applied the ISBE model to RNA-seq data from the Chatila et al. (2022) cohort, comprising 110 rectal cancer patients treated with nCRT. The ISBE classification aligned well with immune groups (IGs) previously established by the authors, with ISBE-High strongly correlating with the IG3 phenotype, characterized by high immune infiltration. Despite this alignment, no significant association was found between ISBE classifications and patient response to nCRT (p = 0.3443, Chi-squared test), indicating that ISBE could not reliably predict treatment outcomes. Furthermore, ISBE classifications showed no correlation with either disease-free survival (DFS) or overall survival (OS). Kaplan-Meier survival analyses confirmed that there were no significant differences in survival outcomes across ISBE groups, with all p-values exceeding the 0.05 significance threshold for both DFS and OS, suggesting ISBE was not a predictor of long-term survival in this cohort.

Conclusões

In this study, the ISBE model did not significantly correlate with OS, DFS, or response to nCRT in rectal cancer patients. While ISBE is aligned with immune infiltration groups, its prognostic value remains inconclusive. In contrast, the Immunoscore (ISB) has proven effective in predicting response and survival in LARC patients undergoing surgery, with potential for guiding conservative treatments. We will refine and validate ISBE in a local cohort to assess its predictive value for nCRT outcomes.

Financiador do resumo

JP FAPESP 2018/15582-9

Palavras Chave

Locally advanced rectal cancer; Immunoscore; Transcriptomics