Abstract
Aim This study analyzed the correlation between immunohistochemical markers in hepatocellular carcinoma cells and the results of in vitro high-throughput drug sensitivity screening, to provide a reference for individualized drug treatment in patients with liver cancer. Methods Seventy-four patients with hepatocellular carcinoma were included in this study from December 2019 to June 2021, and their liver cancer cells were used for in vitro high-throughput drug sensitivity screening. According to the screening results, the patients were divided into relatively sensitive and insensitive groups, and the correlations between sensitivity and immunohistochemistry results were analyzed statistically. Results Alpha-fetoprotein (AFP)-positive liver cancer cells were significantly more sensitive to gemcitabine than AFP-negative cells (χ2 = 6.102, P=0.014). AFP was also positively correlated with sensitivity of liver cancer cells to three combined regimens containing oxaliplatin (L-OHP) and epirubicin (EPI) : L-OHP + EPI + irinotecan + 5-fluorouracil (5-FU), L-OHP + irinotecan + EPI, and L-OHP + EPI (χ2 = 8.168, P=0.004, χ2 = 5.705, P=0.017, and χ2 = 8.275, P=0.004, respectively). Conclusion Gemcitabine and L-OHP + EPI + irinotecan + 5-FU, L-OHP + EPI, and L-OHP + irinotecan + EPI were more effective against AFP-positive compared with AFP-negative liver cancer cells according to in vitro high-throughput drug sensitivity screening. These results may guide the selection of personalized drug treatments for patients with advanced liver cancer in the future but still need further clinical studies to confirm.
Highlights
Multiple or giant tumors and accompanying metastases make surgical treatment impossible [3], and the remaining options in these patients include palliative, down-staging, or systemic treatments, such as transcatheter arterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), radiofrequency and microwave ablation, and targeted therapy and immunotherapy [2, 4]. e single or combined use of these treatments (e.g., TACE combined with sorafenib [5] or apatinib [6], HAIC combined with sorafenib [7]) has achieved some clinical results; the benefits in patients with advanced liver cancer are still not optimistic
We examined the expression of alpha-fetoprotein (AFP), cytokeratin 7 (CK7), glypican 3 (GPC-3), antihepatocyte-specific antigen (HepPar1), and Ki-67. e cells were divided into positive and negative groups for all antigens, except for Ki-67, and Ki-67 ≥ 20% was considered as high expression and
Interventional therapy, targeted therapy, and immunotherapy have all been applied in clinical practice, the occurrence of drug resistance and the high heterogeneity of liver cancer mean that the survival benefits of these treatments are not ideal. e diversification of cytotoxic, targeted, and immune drugs has increased the available treatment options for patients with advanced liver cancer; research into the personalized and targeted treatment of these patients remains in the preliminary stages. e current study aimed to identify immunohistochemical indicators that could guide clinical drug use and provide recommendations for future clinical trials
Summary
According to [1], HCC is the sixth most common cancer globally and the fourth leading cause of cancer-related death. E single or combined use of these treatments (e.g., TACE combined with sorafenib [5] or apatinib [6], HAIC combined with sorafenib [7]) has achieved some clinical results; the benefits in patients with advanced liver cancer are still not optimistic. Is heterogeneity may be reflected in the histological types (e.g., thin trabecular type, thick trabecular type, pseudoglandular type, and compact type), as well as in the cellular phenotype (e.g., clear-cell type, fat-rich type, spindle-cell type, and undifferentiated type) It may be reflected in terms of the tumor differentiation status and growth pattern (e.g., invasion of ambient normal liver tissue, invasion of the capsule, generation of satellite nodules, intrahepatic metastasis, and formation of tumor thrombi) [10]. High-throughput drug sensitivity screening (HDS) is a precision medication technology system for cancer patients. We examined the HDS results for several cytotoxic and targeted drugs and chemotherapy regimens in relation to the immunohistochemical characteristics of liver cancer cells, to identify possible correlations as a reference for clinical treatment
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