Transient-receptor potential (TRP) channels comprise a diverse family of ion channels, which play important roles in regulation of intracellular calcium. Emerging evidence has revealed the critical roles of TRP channels in tumor development and progression. However, we still lack knowledge about the genetic and pharmacogenomics landscape of TRP genes across cancer types. Here, we comprehensively characterized the genetic and transcriptome alterations of TRP genes across >10,000 patients of 33 cancer types. We revealed prevalent somatic mutations and copy number variation in TRP genes. In particular, mutations located in transmembrane regions of TRP genes were likely to be deleterious mutations (p-values < 0.001). Genetic alterations were correlated with transcriptome dysregulation of TRP genes, and we found that TRPM2, TRPM8, and TPRA1 showed extent dysregulation in cancer. Patients with TRP gene alterations were with significantly higher hypoxia scores, tumor mutation burdens, tumor stages and grades, and poor survival. The alterations of TRP genes were significantly associated with the activity of cancer-related pathways. Moreover, we found that the expression of TRP genes were potentially useful for development of targeted therapies. Our study provided the landscape of genomic and transcriptomic alterations of TPRs across 33 cancer types, which is a comprehensive resource for guiding both mechanistic and therapeutic analyses of the roles of TRP genes in cancer. Identifying the TRP genes with extensive genetic alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.

Long non-coding RNAs (lncRNAs) have been demonstrated to be significant in numerous biological processes. Hypertension is a form of cardiovascular disease with at least one billion cases worldwide. The present study sought to compare the differential expression profiles of lncRNAs in the renal cortex of spontaneously hypertensive rats (SHRs) and normotensive Wistar‑Kyoto (WKY) rats. The ipsilateral renal cortex was obtained from 15‑week‑old SHRs and WKY rats whose blood pressures had been monitored. Total RNA was extracted using TRIzol, and lncRNAs and messenger RNAs were profiled by microarray and validated using fluorescent quantitative reverse transcription‑polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the function of differentially expressed genes. Microarray analysis demonstrated that 145 lncRNAs were differentially expressed between SHRs and WKY rats. GO and KEGG pathway analysis indicated that these lncRNAs are involved in numerous biological processes. Thus, lncRNAs may contribute to the pathogenesis of hypertension.

Background: To better understand the difference between traditional breast-conserving surgery (BCS) and oncoplastic surgery (OPS), we conducted a retrospective cohort study involving breast cancer patients who received neoadjuvant chemotherapy (NAC) and then underwent breast conservation at the Fudan University Shanghai Cancer Center. Methods: A retrospective chart review was conducted. All breast cancer patients who received NAC and then underwent traditional BCS or OPS at the Fudan University Shanghai Cancer Center from January 1, 2008, to December 31, 2019, were included. Results: Three hundred ninety-nine breast cancer patients received NAC and underwent traditional BCS, and 99 patients underwent OPS. The average age of the patients in the OPS group was younger than that in the BCS group (43 vs 48 years, P = 0.017). The size of the tumor assessed by ultrasonography at baseline in the OPS group was larger than that in the BCS group (31.3 vs 28.1 mm, P = 0.013). The same trend was observed in the clinical T stage and overall staging assessments before the administration of NAC in these 2 groups. Oncoplastic techniques were more frequently applied when tumors were located in areas with relatively few glands, such as the upper inner quadrant. There were no significant differences in the margins and distributions of pathological types and molecular subtypes between these 2 groups. The rates of pathological complete response were similar in the traditional BCS and OPS groups. Conclusions: Unlike traditional BCS, in breast cancer patients after NAC, the adoption of oncoplastic techniques makes breast conservation feasible, even in patients with large tumors, late stages, and unfavorable tumor locations.

Angiogenesis constitutes a critical rate-limiting determinant of tumor progression in breast cancer (BC). Resistance to conventional anti-angiogenic therapies in BC highlights an unmet need to identify upstream molecular regulators coordinating malignant cell plasticity and vascular remodeling. Lemur tail kinase 3 (LMTK3) is a well-established oncogenic kinase; however, its specific role within the tumor angiogenic microenvironment remains undefined. Here, we identify LMTK3 as a context-dependent driver of angiogenesis through a mesenchymal-epithelial transition (MET) program. By integrating single-cell RNA sequencing with functional validation, we uncover a ‘Simpson’s paradox’ (where a correlation present in different groups disappears or reverses when combined): In mesenchymal-like triple-negative breast cancer (TNBC), LMTK3 promotes a pro-angiogenic, ‘partial EMT’ (p-EMT) state characterized by sustained ERK signaling and elevated secretion of angiogenic factors, including angiogenin. Conversely, in luminal-like cells, LMTK3 enforces a hyperepithelialized state that suppresses angiogenic phenotypes. Consequently, LMTK3 emerges as a central regulator of angiogenic plasticity, and its targeted inhibition offers a promising strategy to abrogate the pro-angiogenic p-EMT state and promote vascular normalization in TNBC.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, due to its aggressive invasiveness and resistance to therapy. The dense, stiff extracellular matrix, composed primarily of collagen I and basement membrane components such as collagen IV and laminin, acts as a mechanical barrier that constrains PDAC invasion. We investigated whether the actin‐related protein (Arp) 2/3 complex, a key actin nucleator, is essential for PDAC cells to overcome extracellular matrix stiffness and facilitate migration. CRISPR/Cas9 knockout of the Arpc4 gene in murine PDAC cell lines derived from Kras ^G12D ‐driven transgenic mice resulted in substantially downregulated all Arp2/3 complex members. Inactivation of Arp2/3 significantly impaired PDAC cell migration, disrupted branched tubular structure formation in collagen I, and inhibited invasive front formation in organoid culture together with tumor‐associated macrophages and fibroblasts. Mechanistically, β1 integrin signaling emerged as a key regulator of Arp2/3‐dependent migration through collagen‐rich matrices. Clinically, elevated expression of Arp2/3 complex components correlates with poor patient survival and basal‐like differentiation subtypes, underscoring its role in disease progression. This study identifies the Arp2/3 complex and β1 integrin signaling as critical mediators of PDAC invasiveness and suggests them as potential therapeutic targets for mitigating PDAC progression.