Chromosomal instability (CIN) covers approximately 65 to 70% of colorectal cancer patients and plays an essential role in cancer progression. However, the molecular features and therapeutic strategies related to those patients are still controversial. R-loop binding proteins (RLBPs) exert significant roles in transcription and replication. Here, integrative colorectal cancer proteogenomic analysis identified two RLBPs subtypes correlated with distinct prognoses. Cluster I (CI), represented by high expression of RLBPs, was associated with the CIN phenotype. While Cluster II (CII) with the worst prognosis and low expression of RLBPs was composed of a high percentage of patients with mucinous adenocarcinoma or right-sided colon cancer. The molecular feature analysis revealed that the active RNA processing, ribosome synthesis, and aberrant DNA damage repair were shown in CI, a high inflammatory signaling pathway, and lymphocyte infiltration was enriched in CII. In addition, we revealed 42 tumor-associated RLBPs proteins. The CI with high expression of tumor-associated proteins was sensitive to drugs targeting genome integrity and EGFR in both cell and organoid models. Thus, our study unveils a significant molecular association of the CIN phenotype with RLBPs, and also provides a powerful resource for further functional exploration of RLBPs in cancer progression and therapeutic application.

Chromosomal Instability (CIN) encompasses approximately 65 %-70 % of colorectal cancer (CRC) patients, playing a pivotal role in tumor progression. However, controversies persist regarding the molecular characteristics and treatment strategies associated with these patients. Integrative colorectal cancer proteogenomic analysis identified DDX18 in colorectal cancer. We investigated the molecular mechanisms underlying the regulation of colorectal cancer by the R-loop binding protein DDX18 using colon cancer tissues, cell lines and patient-derived organoids. Our findings revealed that DDX18 expression positively correlates with the expression of genomic instability marker R-loops. Moreover, heightened DDX18 expression delays the completion of DNA damage repair, leading to an increase in double-strand DNA breaks, thereby promoting genomic instability. Notably, the upregulation of DDX18 enhances sensitivity to DNA-damaging. This study elucidated DDX18 beyond participating in fundamental physiological functions, may play a crucial role in the regulation of genomic stability, and also provides a powerful resource for further functional exploration of DDX18 in cancer progression and therapeutic application.

Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. While common metastatic sites of hepatocellular carcinoma include the lung, bone, and lymph nodes, pharyngeal metastasis is extremely rare. This case report presents a unique case of a patient with hepatocellular carcinoma who developed pharyngeal metastasis. We describe the patient’s clinical course, diagnostic work-up, and treatment strategies and details. We paid special attention to diagnostic difficulties and to ways of its resolving. Additionally, a comprehensive literature review was performed to summarize the characteristics, possible mechanisms, and management of hepatocellular carcinoma pharyngeal metastasis. By presenting this case and reviewing the literature, we aim to raise awareness among clinicians about this rare metastatic manifestation of hepatocellular carcinoma and provide insights into its diagnosis and treatment.

Background: Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. Previous studies have reported that interleukin enhancer–binding factor 3 (ILF3) is involved in the regulation of multiple cancers. This study investigated the molecular mechanisms whereby ILF3 promotes HCC progression. Methods: ILF3 expression levels were determined through immunohistochemistry (IHC) and Western blot (WB) analyses. The biological functions of ILF3 in HCC were evaluated using both in vitro assays and in vivo animal models. Co‐immunoprecipitation (Co‐IP) was carried out to identify HMGCL as a binding partner of ILF3. To clarify the potential molecular pathways underlying ILF3‐mediated regulation of HCC malignant behaviors, protein stability assays and in vitro ubiquitination experiments were performed. Results: ILF3 was significantly upregulated in HCC. The patients with high expression of ILF3 showed poor prognosis in our cohort. ILF3 knockdown inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo in this study. Mechanistically, ILF3 was found to be bound to HMGCL and to accelerate its protein degradation. Additionally, we found that ILF3 promotes HCC cell proliferation and metastasis through HMGCL. Overexpression of HMGCL in ILF3‐upregulated HCC cells could significantly reverse the proliferation and invasion role of ILF3 on HCC cells. Moreover, USP38 was identified as a deubiquitinating enzyme that participates in promoting the stability of HMGCL. ILF3 disrupted the interaction between USP38 and HMGCL, thereby enhancing HMGCL ubiquitination and accelerating its degradation. Conclusion: ILF3 promotes the proliferation and metastasis of HCC by enhancing the ubiquitination of HMGCL by interfering with the interaction between the deubiquitinase USP38 and HMGCL.