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Transcriptomics changes in liver metastatic biopsies of colorectal carcinoma between pre-treated and acquired resistance to Cetuximab [miRNA]

ABSTRACT: Two patients who were newly diagnosed and pathologically confirmed metastatic colorectal cancer were screened for eligibility between August 2011 and December 2013 in Affiliated Hospital, Academy of Military Medical Sciences. They were treated with Cetuximab in combination with FOLFOX regimen and obtained continuous partial responses in more than six months. CT scans of liver lesions were performed every two to eight weeks. The four biopsies were evaluated by two pathologists and were confirmed that the tumor purities were greater than 50%. Each biopsy was subjected to high-throughput RNA and small RNA sequencing to obtain expression profiles of genes and miRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84269 | GEO | 2019/06/20

REPOSITORIES: GEO

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Project description:Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA. Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration. Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumour tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination. FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.

Dataset Information

Transcriptomics changes in liver metastatic biopsies of colorectal carcinoma between pre-treated and acquired resistance to Cetuximab [miRNA]

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