Introduction The prognosis of patients with glioma is dismal. It has been reported that Serpin peptidase inhibitor clade A member 3 (SERPINA3) is associated with the mobility and invasion of tumor cells. Our study was designed to explore the value of SERPINA3 messenger RNA (mRNA) expression in the biological process, prognosis, and immune significance in glioma. Methods We analyzed the biological functions of SERPINA3 through data from the Chinese Glioma Genome Atlas databases. Differentially expressed genes and enrichment analysis were performed and correlations between SERPINA3 expression and immune cell infiltration were analyzed. Further, we validated the expression and the survival prediction role of SERPINA3 by using tissue microarrays and RNAscope in situ hybridization in 321 gliomas. The correlations between the expression and clinical‐pathological parameters as well as other biomarkers were examined. Results Univariate and multivariate regression both indicated that the level of SERPINA3 transcript represented an independent prognostic factor. High levels of SERPINA3 correlated with poor survival in patients with glioma. Expression of SERPINA3 mRNA was observed positively correlated with MCM6, IGFBP2, and FKBP10. Enrichment analysis showed SERPINA3 mainly enriched in immune‐related terms and signaling pathways including MAPK, TNF, P53, PI3K‐Akt, nuclear factor‐κB. Immune infiltration analysis further declare the SERPINA3 expression negatively correlated with levels of Macrophages M1, native CD4+ T cell, monocytes, and Mast cell activated. And overexpression of SERPINA3 correlated with low CD4+ T cell infiltration in glioma tissues. Conclusions SERPINA3 may play a key role in the biological process of glioma cells especially in immune suppression activities. SERPINA3 may serve as an independent survival prediction factor in glioma patients.

Purpose To explore the potential pathogenesis and clinical features of second primary glioblastoma (spGBM) following first primary renal cell carcinoma (fpRCC). Methods Patients with spGBM after fpRCC were enrolled from our institution and the SEER dataset. Sanger sequencing, whole genome sequencing, and immunehistochemistry were used to detect molecular biomarkers. Results Four and 122 cases from our institution and the SEER dataset, respectively, were collected with an overall median age of 69 years at spGBM diagnosis following fpRCC. The median interval time between fpRCC and spGBM was 50.7 months and 4 years, for the four and 122 cases respectively. The median overall survival time was 11.2 and 6.0 months for the two datasets. In addition, spGBM patients of younger age (< 75 years) or shorter interval time (< 1 year) had favorable prognosis (p = 0.081 and 0.05, respectively). Moreover, the spGBM cases were molecularly classified as TERT only paired with TP53 mutation, PIK3CA mutation, EGFR alteration, low tumor mutation burden, and stable microsatellite status. Conclusions This is the first study to investigate the pathogenesis and clinical features of spGBM following spRCC. We found that spGBMs are old-age related, highly malignant, and have short survival time. Moreover, they might be misdiagnosed and treated as brain metastases from RCC. Thus, the incidence of spGBMs after fpRCC is underestimated. Further studies are needed to investigate the underlying molecular mechanisms and clinical biomarkers for the development of spGBM following fpRCC.

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