ABSTRACT
BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.
ABSTRACT
BACKGROUND: College students are vulnerable to suffering from anxiety and depression. Moreover, mental disorders can contribute to drug consumption or inappropriate use of prescribed drugs. Studies on this topic in Spanish college students are limited. This work analyses anxiety and depression and psychoactive drug intake pattern in the post-COVID era in college students. METHODS: An online survey was conducted among college students from UCM (Spain). The survey collected data including demographic, academic student perception, GAD-7 and PHQ-9 scales, and psychoactive substances consumption. RESULTS: A total of 6798 students were included; 44.1 % (CI95%: 42.9 to 45.3) showed symptoms of severe anxiety and 46.5 % (CI95%: 45.4 to 47.8) symptoms of severe or moderately severe depression. The perception of these symptoms did not change after returning to face-to-face university classes in the post-COVID19 era. Despite the high percentage of cases with clear symptoms of anxiety and depression, most students never had a diagnosis of mental illnesses [anxiety 69.2 % (CI95%: 68.1 to 70.3) and depression 78.1 % (CI95%: 77.1 to 79.1)]. Regarding psychoactive substances, valerian, melatonin, diazepam, and lorazepam were the most consumed. The most worrying issue was the consumption of diazepam, 10.8 % (CI95%: 9.8 to 11.8), and lorazepam, 7.7 % (CI95%: 6.9 to 8.6) without medical prescription. Among illicit drugs, cannabis is the most consumed. LIMITATIONS: The study was based on an online survey. CONCLUSIONS: The high prevalence of anxiety and depression aligned with poor medical diagnosis and high intake of psychoactive drugs should not be underestimated. University policies should be implemented to improve the well-being of students.
