Comprehensive molecular profiling of intrahepatic cholangiocarcinoma in the Chinese population and therapeutic experience

Abstract

Background: The genomic alterations of intrahepatic cholangiocarcinoma (ICC) in the Chinese population have not been fully revealed. Molecular profiling may provide a reference for clinical management, especially targeted therapy. Methods: A retrospective study was conducted in 122 ICC patients. All patients' samples underwent next-generation sequencing (NGS), which analyzed 417 genes. The genetic characteristics, clinical management and therapeutic responses were analyzed. Results: The most commonly mutated genes were TP53 (34%), KRAS (25%) and ARID1A (17%). Targeted agents were used referring to molecular profiling, in combination with chemotherapy. Twenty-two patients with wild-type KRAS/ NRAS/BRAF were treated with cetuximab. The disease control and response rates were 78% and 47%, respectively, which were higher than those achieved with chemotherapy alone (72% and 11%, P = 0.16). Fifty-four patients underwent anti-VEGF treatment with bevacizumab. The disease control and response rates were 85% and 60%, respectively. Better therapeutic efficiency (P = 0.001) and longer progression-free survival (PFS) were observed in the bevacizumabtreated group compared to chemotherapy alone group (15.4 and 6.7 months, respectively; P = 0.04). The PFS of ten patients who underwent hepatectomy after combined treatment with chemotherapy and bevacizumab was longer than that of 139 patients who underwent surgical treatment (28.9 vs 18.0 months, P = 0.03). Two patients (1.6%) had signatures of microsatellite instability (MSI-H), and both benefited from immunotherapy. Conclusions: This study provides an overview of genetic alterations in Chinese ICC patients and indicates the potential clinical implications for NGS-based personalized therapies.

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma

“…Regarding VEGF expression, it was found that its overexpression was associated with decreased survival rate though it did not lead to a significant difference. These findings were also in line with those of an Asian study done by Wang et al (Wang et al, 2020). Several factors regulate the occurrence and development of CCA, such as proliferation, apoptosis, and tumor angiogenesis, which are closely related to biological behavior of .…”

The Curious Case of the HepG2 Cell Line: 40 Years of Expertise

“…Hepatic AS and ICCA also have a TP53 gene mutation associated with reduced survival [ 65 , 66 , 67 ]. In ICCA, mutations are also often observed in the KRAS and ARID1A genes [ 68 , 69 ], the proteins involved in the cell signaling pathways that control cell growth, maturation, and death. Sometimes, mutations occur in genes involved in Wnt signaling, i.e., CTNNB1, AXIN1, and APC [ 70 , 71 ].…”

Non-surgical treatment of hilar cholangiocarcinoma

“…The goal of molecular research is to develop a tailored therapy protocol based on molecular profiling, in order to minimize toxicity and optimize efficiency. Only recently, Wang et al [ 59 ] published a retrospective study investigating the molecular profile of intrahepatic cholangiocarcinoma in the Chinese population, using next-generation sequencing. The identified genomic alterations were used for personalized therapy and targeted or immunotherapy agents demonstrated superior survival and tumor response outcomes compared to standard chemotherapy[ 59 ].…”

“…Only recently, Wang et al [ 59 ] published a retrospective study investigating the molecular profile of intrahepatic cholangiocarcinoma in the Chinese population, using next-generation sequencing. The identified genomic alterations were used for personalized therapy and targeted or immunotherapy agents demonstrated superior survival and tumor response outcomes compared to standard chemotherapy[ 59 ]. Moreover, genome sequencing and animal model studies suggest that gain-of-function mutations in the IDH gene, could be involved in a subset of cancers with inflammatory signature and trials with IDH inhibitors are ongoing[ 60 ].…”