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Identifying molecular features is an essential component of the management and targeted therapy of brain metastases (BMs). The molecular features are different between primary lung cancers and BMs of lung cancer. Here we report the DNA and RNA mutational profiles of 43 pathological samples of BMs. In addition to previously reported mutational events associated with targeted therapy, PTPRZ1‐MET, which was previously exclusively identified in glioma, was present in two cases of BMs of lung cancer. Furthermore, MET exon 14 skipping may be more common (6/37 cases) in BMs of lung cancer than the frequency previously reported in lung cancer. These findings highlight the clinical significance of targeted DNA plus RNA sequencing for BMs and suggest PTPRZ1‐MET and MET exon 14 skipping as critical molecular events that may serve as targets of targeted therapy in BMs. [ABSTRACT FROM AUTHOR]

Background: Gliomas are aggressive tumors with various molecular and clinical characteristics and exhibit strongly resistance to radio-chemotherapy. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein, which was reported in many cancers, modulating cancer-associated immune responses, while the role of PD-L2 in gliomas remained unclear. Herein, we aimed to investigate the biological behaviors and clinical prognostic values of PD-L2 in gliomas. Methods: Totally, we enrolled RNA sequencing data of 325 glioma samples from Chinese Glioma Genome Atlas (CGGA) as training cohort and RNA expression data of 1032 samples from The Cancer Genome Atlas (TCGA) dataset as validation cohort in this research. Then, the clinical and molecular characteristics, and the prognostic value of PD-L2 were analyzed. Results: We found that PD-L2 expression level was significantly upregulated in higher grade glioma and IDH wild-type glioma. Receiver Operating Characteristic (ROC) analysis revealed that PD-L2 was a potential indicator of mesenchymal subtype. PD-L2 exhibited tight relationship with immune response and immune-modulating process in glioma. Moreover, PD-L2 expression level could predict unfavorable prognoses of patients independent of age, grade, IDH status and 1p/19q status. Conclusions: Our study revealed that PD-L2 was closely related with inflammation and immune response. Patients with lower PD-L2 expression level tended to experience improved survival. Targeting PD-L2 may become a valuable approach for the treatment of gliomas in clinical practice. [ABSTRACT FROM AUTHOR]

Tumor recurrence is a common clinical dilemma in diffuse gliomas. We aimed to identify a recurrence-related signature to predict the prognosis for glioma patients. In the public Chinese Glioma Genome Atlas dataset, we enrolled multi-omics data including genome, epigenome and transcriptome across primary and recurrent gliomas. We included RNA sequencing data from the batch 1 patients (325 patients) as the training set, while RNA sequencing data from the batch 2 patients (693 patients) were selected as the validation set. The R language was used for subsequent analysis. Compared with primary gliomas, more somatic mutations and copy number alterations were revealed in recurrent gliomas. In recurrent gliomas, we identified 113 genes whose methylation levels were significantly different from those of the primary glioma. Through differential expression analysis between primary and recurrent gliomas, we screened 121 recurrence-related genes. Based on these 121 gene expression profiles, consensus clustering of 325 patients yielded two robust groups with different molecular and prognostic features. We developed a recurrence-related risk signature with the lasso regression algorithm. High-risk group had shorter survival and earlier tumor recurrence than the low-risk group. Compared with traditional indicators, the signature showed better prognostic value. In addition, we constructed a nomogram model to predict glioma survival. Functional characteristics analysis found that the signature was associated with cell division and cell cycle. Immune analysis suggested that immunosuppressive status and macrophages might promote glioma recurrence. We demonstrated a novel 18-gene signature that could effectively predict recurrence and prognosis for glioma patients., Competing Interests: None., (AJCR Copyright © 2021.)

The impact of sexual dysfunction (SD) is distressing to many male patients with pituitary adenomas which affect both physical and psychological health. The research explored to identify risk factors affecting sexual function and the prognosis of male patients with pituitary adenomas. Two hundred and fifty-four male patients, who aged between 18 and 60 (mean ± s.d.: 44.16 ± 10.14) years and diagnosed with pituitary adenomas, were retrospectively analyzed. One hundred and fifty-nine patients (62.6%) complained of SD prior to surgery. The mean International Index of Erectile Function (IIEF-5) in patients with giant adenomas was 16.13 ± 2.51, much smaller than those with microadenomas or macroadenomas (P < 0.05). All the patients showed significant improvement in terms of erectile dysfunction (ED) following surgery (P < 0.05). In addition, complete resection achieved a higher degree of SD relief than partial resection. The incidence of SD in functioning pituitary adenomas (FPAs) was much higher than that in nonfunctioning pituitary adenomas (NFPAs) (P < 0.05). In addition, compared with NFPAs, males with prolactinomas (82.8%) had the higher prevalence of SD and significantly improvement following surgical intervention (P < 0.05). An inverse relationship was identified between decreasing testosterone levels and increasing incidence of SD before surgery (P < 0.05). There was no significant difference between 6 months and 12 months after surgery in serum testosterone level (P > 0.05). Our results indicated that surgical therapy could be optimized for improvements in SD and that testosterone levels can be used as a sensitive indicator to predict the recovery rate of sexual function in patients with pituitary adenomas following surgery and the serum testosterone level will stay stable in 6 months after surgery.

Objective: To employ whole-genome messenger RNA profiling to identify the genes involved in malignant progression in glioma., Methods: The whole genome expressed genes were profiled in 220 glioma patients from the Chinese Glioma Genome Atlas (97 LGGs and 123 HGGs). The differential expressed genes between LGG and HGG were identified by SAM analysis. Microarray data were validated by immunohistochemistry., Results: Among all the detected genes, the genes up-regulated mostly in high-grade glioma were IGFBP-2, CKLF, PTTG1, OSTCL and PTTG2 while those down-regulated mostly SEC31, RRP7B, HOOK3, SNRPN and CSMD3. Validation of IGFBP-2 with immunohistochemical staining showed a good correlation with the microarray data., Conclusion: A panel of potential genes of malignant transformation may serve as future targets of gene therapy for glioma.