TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

Prediction of the response of ocular adnexal lymphoma to chemotherapy using combined pretreatment dynamic contrast-enhanced and diffusion-weighted MRI.

Background There are no established biomarkers predictive of the efficacy of treatment for ocular adnexal lymphoma (OAL). Purpose To evaluate the effectiveness of pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the response of OAL to chemotherapy. Material and Methods Twenty-one patients, who were pathologically diagnosed with OAL, were retrospectively analyzed. According to the National Comprehensive Cancer Network (NCCN) response evaluation criteria for non-Hodgkin's lymphoma, patients were divided into responders (n = 14) and non-responders (n = 7). The volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (Ve), and apparent diffusion coefficient (ADC) were computed. Two independent-sample tests were applied for statistical analysis. For significantly different parameters, receiver-operator characteristics curve analysis was performed. Results The Ktrans value (min-1), Kep value (min-1), and ADC value (10-3 mm2/s) were 0.76 ± 0.36 vs. 0.47 ± 0.18 (mean ± SD), 4.43 ± 1.29 vs. 3.14 ± 1.37, and 0.51 ± 0.12 vs. 0.66 ± 0.15, respectively, in the responders and non-responders groups. Significant differences were found between the two groups regarding these parameters ( P < 0.05). However, no significant difference was observed in Ve (min-1) between the groups ( P > 0.05). Ktrans, Kep, and ADC had a moderately predictive sensitivity or specificity. When Ktrans and ADC or the three parameters were combined, a considerably higher sensitivity (85.7%) and specificity (85.7%) with a significant discriminative accuracy (area under the curve = 0.929; P = 0.002) was found. Conclusion Ktrans, Kep, and ADC could potentially predict OAL response to chemotherapy. A combination of these DWI and DCE-MRI quantitative parameters might increase sensitivity and specificity.