Oncology Letters最新文献

Immunotherapy provides durable responses for locally advanced esophageal carcinoma clinical therapy in numerous patients. However, the mechanisms of resistance to immunotherapy have not been elucidated. The phenomenon of the histological transformation of non-small cell lung cancer to small cell lung cancer resulting in resistance to immune checkpoint inhibitors (ICIs) has been reported. It remains unclear whether ICIs or chemotherapy could cause a similar transformation from esophageal squamous cell carcinoma (ESCC) to esophageal neuroendocrine carcinoma (ENEC). The present study report the case of a patient initially diagnosed with stage II ESCC who underwent radical surgery after three cycles of neoadjuvant therapy with cisplatin, albumin bound paclitaxel and ICIs. Immunohistochemical staining confirmed the absence of the SCC component and the presence of the NEC component, with negativity for CK5/6 and tumor protein p40, but positive expression of tumor protein p53, pan-cytokeratin, synaptophysin and CD56. The patient was followed up for 5 months with no treatment or postoperative complications. In conclusion, histological transformation to ENEC is a potential mechanism of acquired resistance to ICIs in ESCC. Prospective larger studies are warranted to further characterize ESCC-to-NEC transformation on use of ICIs.

Tumor invasion and metastasis are the processes that primarily cause adverse outcomes in patients with cervical cancer. Cancer-associated fibroblasts (CAFs), which participate in cancer progression and metastasis, are novel targets for the treatment of tumors. The present study aimed to assess the heterogeneity of CAFs in the cervical cancer microenvironment through single-cell RNA sequencing. After collecting five cervical cancer samples and obtaining the CAF-associated gene sets, the CAFs in the cervical cancer microenvironment were divided into myofibroblastic CAFs and extracellular (ec)CAFs. The ecCAFs appeared with more robust pro-tumorigenic effects than myCAFs according to enrichment analysis. Subsequently, through combining the ecCAF hub genes and bulk gene expression data for cervical cancer obtained from The Cancer Genome Atlas and Gene Ontology databases, univariate Cox regression and least absolute shrinkage and selection operator analyses were performed to establish a CAF-associated risk signature for patients with cancer. The established risk signature demonstrated a stable and strong prognostic capability in both the training and validation cohorts. Subsequently, the association between the risk signature and clinical data was evaluated, and a nomogram to facilitate clinical application was established. The risk score was demonstrated to be associated with both the tumor immune microenvironment and the therapeutic responses. Moreover, the signature also has predictive value for the prognosis of head and neck squamous cell carcinoma, and bladder urothelial carcinoma, which were also associated with human papillomavirus infection. In conclusion, the present study assessed the heterogeneity of CAFs in the cervical cancer microenvironment, and a subgroup of CAFs that may be closely associated with tumor progression was defined. Moreover, a signature based on the hub genes of ecCAFs was shown to have biomarker functionality in terms of predicting survival rates, and therefore this CAF subgroup may become a therapeutic target for cervical cancer in the future.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m² nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m² gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

Worldwide, liver cancer is the most frequent fatal malignancy. Liver cancer prognosis is poor because patients frequently receive advanced-stage diagnoses. The current study aimed to establish the potential pharmacological targets and the biological networks of scutellarein (SCU) in liver cancer, a natural product known to have low toxicity and side effects. To identify the differentially expressed genes between SCU-treated and SCU-untreated HepG2 cells, RNA sequencing (RNA-seq) was carried out. A total of 463 genes were revealed to have differential expression, of which 288 were upregulated and 175 were downregulated in the group that had received SCU treatment compared with a control group. Gene Ontology (GO) enrichment analysis of associated biological process terms revealed they were mostly involved in the regulation of protein heterodimerization activity and nucleosomes. Interaction of protein-protein network analysis using Search Tool for the Retrieval of Interacting Genes/Proteins resulted in two crucial interacting hub targets; namely, histone H1-4 and protein tyrosine phosphatase receptor type C. Additionally, the crucial targets were validated using western blotting. Overall, the present study demonstrated that the use of RNA-seq data, with bioinformatics tools, can provide a valuable resource to identify the pharmacological targets that could have important biological roles in liver cancer.