TICRR serves as a prognostic biomarker in lung adenocarcinoma with implications in RNA epigenetic modification, DDR pathway, and RNA metabolism.

Purpose: TOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells. Methods: RT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions. Results: TICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management. Conclusions: Taken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

Insights from a patient with chronic lymphocytic leukemia complicating ALK+ anaplastic large cell lymphoma.

Chronic lymphocytic leukemia (CLL) that transforms into a more aggressive lymphoma has been termed Richter syndrome (RS). CLL with T-cell neoplasia is rarely reported; those with ALK+ anaplastic large cell lymphoma (ALCL) are also exceedingly rarely reported. A 63-year-old woman from the south of China presented with generalized lymphadenectasis and fever; she already had a prior diagnosis of CLL 9 years ago. As per her current diagnosis, it was CLL with ALK+ ALCL. The two-lymph node and bone marrow biopsies presented two types of cellular groups: i) left cervical lymph node biopsy suggested CLL (Ki67: 10%), along with bone marrow biopsy exhibited enhancement of the small lymphocytes (30%) with scant cytoplasm, round or irregular cell nuclei, and massive amounts of chromatin. Large cells (< 1%) that expressed CD30 and ALK were visible; The results of immunohistochemistry were as follows: CD20 (weak positive); PAX5 (positive); CD23 and CD5 (weak positive); and CD3, CD10, and CyclinD1 (negative); ii) left supraclavicular lymph node biopsy suggested ALK+ ALCL (Ki67: 70%). The final diagnosis was CLL with ALCL. The mechanisms of this condition are not fully understood, which might be associated with chronic stimulation of T cells by CLL cells along with immune dysfunction.

Expression of Tspan-1 gene in patients with advanced gastric cancer.

The present study investigated the correlations of the Tspan-1 gene expression with the clinical characteristics and survival prognoses of patients with advanced gastric cancer. A total of 150 patients with advanced gastric cancer were enrolled in the present study, of whom 84 were at stage II and 66 were at stage III according to the tumor node metastasis (TNM) staging; the immunohistochemical staining method and the semi-quantitative PCR method were used to detect the positive expression rates and mRNA relative expression levels of Tspan-1, vascular endothelial growth factor (VEGF), E-cadherin and N-cadherin. The positive expression rates of Tspan-1, VEGF, E-cadherin and N-cadherin were 58.0% (87 patients), 50.0% (75 patients), 28.0% (42 patients) and 53.3% (80 patients), respectively. The positive expressions and mRNA levels of Tspan-1, VEGF, E-cadherin and N-cadherin were not correlated with sex or age (P>0.05), but associated with the cancer state (stage II or stage III) and maximum tumor diameter (P<0.05). With the increase of stage and tumor diameter, the positive rates and mRNA levels of Tspan-1, VEGF and N-cadherin were increased, while those of E-cadherin were decreased. Among patients with stage II/III advanced gastric cancer, those with positive expression of Tspan-1, VEGF and N-cadherin had lower median survival time and survival rates than patients with negative expressions, while patients with positive expression of E-cadherin had higher median survival time and survival rate than those with negative expression (P<0.05). The high expression of Tspan-1 gene is associated with the TNM staging of advanced gastric cancer and the tumor diameter, influences the survival prognosis, and may involve the processes of angiogenesis and epithelial-mesenchymal transition.