Identification of secretory pathway-related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma.

BACKGROUND: The dysfunction of secretory pathways may represent biomarkers or therapeutic targets of cancer. The hepatocellular carcinoma (HCC) phenotype was studied in relation to the genes in the secretory pathway and to screen for a combination of genes that may be a viable therapeutic target for HCC and connected to the pathophysiological features of the tumor. METHODS: Using the HCC information from The Cancer Genome Atlas, somatic mutation and prognostic association analysis were performed on the secretory pathway genes. Based on prognostic genes in the secretory pathway, the samples were consensus clustered, and a Random Forest model was built. The clinical characteristics, tumor mutation burden, functional status and potential responses to immunotherapy and tumor suppressor medications of various subtypes and risk groups were discussed. RESULTS: Of the 84 genes for secretory pathway, 32 were prognostic genes related to HCC, which divided HCC into two categories: C1 and C2. By comparing the two types of HCC samples, it was found that the survival outcome of C1 was inferior, with stronger adaptive and innate immunity, but less sensitive to immunotherapy than C2. The constructed prognostic signature included seven of the 32 prognostic genes in the secretory pathway, which showed significant correlation with the prognosis, somatic mutation, biological pathway status, potential response to immunotherapy and sensitivity of 72 tumor suppressor drugs from different HCC cohorts, and had a feasible prognostic effect for 31 types of cancer and immunotherapy cohorts. CONCLUSIONS: In this study, HCC was divided into two molecular subtypes according to prognostic genes in the secretory pathway, and seven of them were combined into one signature, which produced significant results in evaluating the prognosis of different HCC cohorts, pan-cancer cohorts and immunotherapy cohorts, and had potential guiding significance for prophylactic immunotherapy in patients with HCC.

[Changes of peripheral blood estradiol and testosterone in early stage after trauma].

OBJECTIVE: To explore the correlation of serum estradiol, testosterone and their ratio to the injury severity score (ISS) and Glasgow coma score (GCS) in patients with multiple traumatic injuries. METHODS: The serum levels of estradiol and testosterone were determined by radioimmunoassay double antibody precipitation method in 95 patients with multiple traumatic injuries within 24 h after trauma. The patients were grouped according to the ISS or GCS (in cases with craniocerebral injury) for comparison of the serum estradiol and testosterone levels with those in 15 normal individuals. RESULTS: In the acute stage of multiple trauma, a distinct declination of testosterone and a marked increment of estradiol were observed, and the changes were closely related to the severity of the trauma .The serum levels of estradiol and testosterone and their ratio differed significantly between patients with severe trauma (ISS>25) and the other groups (P<0.01), and also between patients with craniocerebral injury (with GCS of 3-5 or 5-8) and the other groups (P<0.01). CONCLUSION: Serum estradiol and testosterone levels and their ratio are correlated to the severity of trauma and craniocerebral injuries, and may serve as indicators for evaluating the trauma severity and prognosis of the traumatic patients.