Volume 37 · Issue 05 · 2021

With the continuous improvement of diagnosis and treatment technology, the focus of acoustic neuroma surgery has shifted from reducing surgical mortality to improving the retention rate of cranial nerve function^[1,2,3,4]。 Because the cochlear nerve function of most patients has been lost to varying degrees before operation, it is generally difficult to retain hearing; However, facial nerve function is rarely abnormal before operation, and it is expected to preserve facial nerve function after tumor resection. The preservation of facial nerve function depends not only on the physician's skilled surgical skills, but also on the good cooperation with the neuroelectrophysiological monitoring team^[5,6], also depends on the correct treatment after different degrees of facial nerve injury. However, the current reality is that a considerable proportion of acoustic neuroma surgical teams lack intraoperative neuroelectrophysiological monitoring assistance, and mainly rely on the experience of surgeons; There is also a lack of scientific and reasonable repair techniques after facial nerve injury. Therefore, the probability of facial paralysis in patients with acoustic neuroma after operation is still very high, and some patients will remain with different degrees of facial nerve dysfunction^[7,8]。 At present, there is still a lack of expert consensus or guidelines on the prevention and treatment of facial paralysis during perioperative period of acoustic neuroma in China. In view of this, we organized multi-disciplinary experts from across the country to jointly write this consensus, in order to standardize the protection of facial nerve during the perioperative period of acoustic neuroma and improve the functional reconstruction level after facial nerve injury.

To investigate the factors influencing prognosis of patients with giant invasive pituitary adenomas who underwent surgical treatment.

Clinical data of 84 patients with giant invasive pituitary adenomas who underwent surgical treatment at Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University from April 2011 to December 2016 were retrospectively analyzed. Univariate and multivariate logistic regression analysis were used to explore the influencing factors of the degree of tumor resection. Kaplan-Meier analysis and multivariate Cox regression analysis were used to investigate the influencing factors of tumor progression.

Among 84 patients, total resection was achieved in 13 cases (15.5%), near-total resection in 40 cases (47.6%) and subtotal resection in 31 cases (36.9%). There were 89.3% (75/84) of the patients who had been followed up for 15-83 months (46.8±19.0 months). There was no perioperative death, and 2 patients (2.4%) died due to surgical complications within 3 months. Univariate analysis showed that previous surgery or radiotherapy, maximal diameter of tumor, tumor shape, tumor invasion degree to the cavernous sinus, whether the tumor invaded the posterior cranial fossa, the enhancement characteristics of the lesions on MRI and the tumor texture could affect the degree of tumor resection (all P<0.05). Multivariate logistic regression analysis showed that the tumor invasion degree to the cavernous sinus (OR=0.089, 95%CI: 0.009-0.850, P=0.036) and tumor texture (OR=0.246, 95%CI: 0.077-0.786, P=0.018) were independent risk factors for tumor resection. Among 84 patients, 14 cases had tumor progression during the follow-up period. Log-rank analysis showed that the tumor resection degree, the presence of mitosis and Ki-67 index in pathological examination might be related to tumor progression (all P<0.05). Multivariate Cox analysis showed that the tumor resection degree (HR=0.316, 95%CI: 0.107-0.932, P=0.037) was a protective factor for tumor progression, and the presence of mitosis (HR=5.064, 95%CI: 1.726-14.859, P=0.003) was an independent risk factor for tumor progression.

For giant invasive pituitary adenomas, it is not easy to achieve total resection for those with a high degree of invasion to the cavernous sinus (Knosp grade 3-4) and tough texture. The tumor with high degree of tumor resection is not liable to progress, while the tumor with mitotic appearance in pathological examination has a tendency to progress.

To investigate the clinical efficacy of supraorbital keyhole approach via a forehead wrinkle incision in resection of tumors in anterior skull base and sellar region.

A retrospective study was conducted on the clinical data of 62 patients with tumors located in anterior skull base and sellar region who underwent surgery through supraorbital keyhole approach via a forehead wrinkle incision at Neurosurgery Department of the First Affiliated Hospital of Anhui Medical University from January 2017 to February 2020. All patients underwent MRI plain scan and enhanced scan before operation, including 49 cases of meningioma (24 cases of olfactory groove meningioma, 18 cases of tuberculum sellae meningioma and 7 cases of sphenoid ridge meningioma), 8 cases of craniopharyngioma and 5 cases of pituitary adenoma. According to the size and growth of tumor, skin incision and bone flap position were designed individually. Postoperative imaging data and clinical symptoms were used to evaluate the total resection rate and the incidence of complications, and the satisfaction of patients with regard to the aesthetic of forehead wrinkle incision was investigated. The tumor recurrence rate and survival rate were followed up 3 months after operation.

Among the 62 patients, total resection was achieved in 54 cases (87.1%) and subtotal resection in 8 cases (12.9%). There was no surgical death. All 62 cases were confirmed by pathological examination. The improvement rate of headache, visual acuity, olfactory symptoms, vertigo, numbness and walking instability was 85.7% (24/28), 13/14, 13/15, 5/6, 4/5; the patients with satisfaction with regard to the aesthetic of forehead wrinkle incision accounted for 87.1% (54/62). All 62 patients were followed up for 18.0±5.6 months (1-36 months). No patients died during the follow-up period, the survival rate was 100%, The dumbness of forehead and supraorbital area occurred in 4 cases post operation relieved or disappeared at 3 months follow-up. 2 (3.2%) cases of pituitary adenoma recurred, and no recurrence was found after the second operation.

Supraorbital keyhole approach via a forehead wrinkle incision for anterior skull base and sellar region tumor resection can not only provide enough surgical field and the same total resection rate as conventional craniotomy, but also significantly improve the clinical symptoms.

To explore the relationship between radiotherapy dose and survival prognosis of patients with supratentorial diffuse glioma with different ataxia telangiectasia mutated (ATM) gene expression levels.

The transcriptome data and clinical data of 87 patients with supratentorial diffuse glioma in the Chinese Glioma Genome Atlas database were retrospectively analyzed. All patients received three-dimensional conformal radiotherapy or intensity-modulated conformal radiotherapy. The expression of ATM gene was detected by transcriptome sequencing, and patients were divided into high expression group and low expression group according to the median of ATM gene expression. Univariate and multivariate Cox regression analysis methods were used to determine whether patients aged >40 years old, male, astrocytoma, isocitrate dehydrogenase ( IDH) mutation, co-deletion of chromosome 1p/19q, and radiotherapy dose were independent influencing factors of survival prognosis in the two groups of patients.

The median (quartiles) of ATM gene expression in 87 patients was 15.0(11.1, 20.8). The median radiation dose (quartiles) of patients in the ATM gene low expression group (n=44) was 54.0 (50.4, 55.8) Gy. The results of univariate analysis showed that astrocytoma was a risk factor for progression-free survival (P=0.036); the radiation dose was a protective factor for progression-free survival and overall survival (both P<0.05). The results of multivariate Cox regression analysis showed that astrocytoma (HR=4.775, 95%CI: 1.104-20.652, P=0.036) was an independent risk factor for progression-free survival; the radiation dose was the independent protective factor for progression-free survival (HR=0.847, 95%CI: 0.761-0.942, P=0.002) and overall survival (HR=0.844, 95%CI: 0.739-0.963, P=0.012). The median (quartile) of radiotherapy dose of patients in the ATM gene high expression group (n=43) was 54.0 (50.4, 57.6) Gy. The results of univariate and multivariate Cox regression analysis revealed that the dose of radiotherapy did not affect progression-free survival or overall survival (all P>0.05).

For patients with low ATM gene expression, increasing the dose of radiotherapy can improve the survival prognosis of patients with supratentorial diffuse glioma.

To investigate the distribution of T-lymphocyte subsets and natural killer (NK)cells activity in peripheral blood from patients with pituitary adenomas and its clinical significance.

A total of 215 patients with pituitary adenomas who were admitted to Department of Neurosurgery, the First Affiliated Hospital of Soochow University from March 2010 to October 2016 were prospectively enrolled in this study. In the same period, 95 healthy subjects were included as the healthy control group (referred to as the control group). Flow cytometry was used to detect the proportions of CD3⁺ , CD3⁺ CD4⁺ , CD3⁺ CD8⁺ , CD3⁺ CD25⁺ , CD3⁺ CD69⁺ , CD3⁺ HLA^-DR⁺ , CD3^-HLA^-DR⁺ and CD3^-CD(16+ 56)⁺ (NK)cells in the peripheral blood of patients with different types of pituitary adenomas and the control group, which were compared between groups. The relationship between different proportions of lymphocyte subsets and clinical characteristics of patients with pituitary adenomas was explored.

In the pituitary adenoma group (215 cases), the proportion of CD3⁺ cells in peripheral blood was lower than that in the control group, while CD3⁺ CD25⁺ and CD3⁺ HLA^-DR⁺ cells were higher than the control group, and the differences were statistically significant (all P<0.05). Compared with the control group, (1) the proportion of CD3⁺ cells in peripheral blood of patients with non-functioning adenoma decreased, while the proportion of CD3⁺ CD25⁺ and CD3⁺ HLA^-DR⁺ cells increased (all P<0.05); (2) in the growth hormone(GH) adenoma and prolactin(PRL) adenoma patients, the proportions of CD3⁺ CD8⁺ , CD3⁺ CD25⁺ and CD3⁺ HLA^-DR⁺ cells increased, while the proportion of NK cells decreased (all P<0.05); (3) in patients with adrenocorticotropic hormone (ACTH) adenomas, the proportions of CD3⁺ CD4⁺ cells and NK cells decreased, while the proportions of CD3⁺ CD8⁺ , CD3⁺ CD25⁺ , CD3⁺ CD69⁺ and CD3⁺ HLA^-DR⁺ cells increased (all P<0.05). The proportion of CD3⁺ cells in the peripheral blood of patients with GH cell adenoma, gonadotropin cell adenoma, and naked cell adenoma (based on the 2017 WHO Classification of Pituitary Adenoma) was lower than that of the control group (all P<0.05). The proportion of NK cells in patients with GH cell adenoma, ACTH cell adenoma, multihormonal and dual hormone cell adenoma was lower than that of the control group (allP<0.05). The proportions of CD3⁺ CD25⁺ and CD3⁺ HLA^-DR⁺ cells in patients with GH cell adenoma, ACTH cell adenoma, PRL cell adenoma, gonadotropin cell adenoma, naked cell adenoma, multihormonal and dual hormone cell adenomas were higher than those in the control group (all P<0.05). In the PRL cell adenoma, multihormonal and dual hormone cell adenoma groups, the proportion of CD3^-HLA^-DR⁺ cells was lower than that of the control group (P<0.05). The proportion of CD3⁺ cells in the giant pituitary adenoma group (tumor diameter >4 cm) was lower than that in the large adenoma group (1-4 cm) and microadenoma group (<1 cm) (both P<0.05). Compared with the non-invasive group, the proportion of CD3⁺ cells in the invasion group decreased, while the proportion of CD3⁺ CD25⁺ cells increased (both P<0.05). The proportion of NK cells in patients with recurrent pituitary adenoma was lower than that in patients with primary pituitary adenoma (P<0.05).

Patients with different types of pituitary adenomas have changes in immune function, which are mainly manifested as the function suppression of cellular immunity or NK cell. The suppression of immune function in patients with pituitary adenomas may be related to tumor burden, tumor invasiveness and recurrence.

To investigate the influencing factors for acute hemorrhagic apoplexy in pituitary adenoma.

A retrospective analysis was conducted on the clinical data of 319 patients with pituitary adenomas undergoing surgery at Department of Neurosurgery, the First Affiliated Hospital of Kunming Medical University from January 2015 to December 2017. According to the presence or absence of acute hemorrhagic apoplexy in pituitary adenomas, the patients were divided into apoplexy group (60 cases) and non-apoplexy group (259 cases). Univariate and multivariate logistic regression analyses were used to determine whether age, gender, hypertension, diabetes, tumor diameter, tumor type, recurrent tumor and other factors were the influencing factors of acute hemorrhagic apoplexy in pituitary adenomas. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to identify the best cut-off value of risk factors for predicting pituitary adenoma apoplexy.

The results of univariate analysis showed that there was no significant difference in gender, age, diabetes or tumor type (all P>0.05), while the differences between the two groups in hypertension, tumor diameter classification and recurrent tumor were statistically significant (allP<0.05). Multivariate logistic regression analysis results showed that hypertension (OR = 2.270, 95% CI: 1.090-4.728, P=0.029), tumor diameter (OR =1.087, 95%CI: 1.048-1.126, P<0.001) and recurrent tumor(OR=3.266, 95%CI: 1.343-7.944, P=0.009) were independent risk factors for apoplexy of pituitary adenomas. The ROC curve of tumor diameter predicting pituitary adenoma apoplexy showed that AUC value was 0.718 (95% CI: 0.658-0.779, P<0.001), the best cut-off value was 24.5 mm, the sensitivity was 85%, and the specificity was 45.6%. There were 167 cases with tumor diameter≤25 mm, including 16 cases with acute hemorrhagic apoplexy in pituitary adenoma and 151 cases without apoplexy. There were 152 cases with tumor diameter>25 mm, including 44 cases with pituitary adenoma apoplexy and 108 cases without apoplexy. Tumor diameter>25 mm was a risk factor for acute hemorrhagic apoplexy in pituitary adenomas (OR = 3.845, 95%CI: 2.062-7.170, P<0.001).

Patients with hypertension, tumor diameter>25 mm and tumor recurrence have a high incidence of acute hemorrhagic apoplexy in pituitary adenomas.

To study the relationship between cervical semispinous muscle atrophy and loss of cervical lordosis following cervical laminae recapping.

The clinical data of 40 patients who underwent cervical spinal tumor resection and laminae recapping at Department of Neurosurgery, Peking University Third Hospital from January 2010 to December 2018 were retrospectively analyzed. All patients were followed up for more than 12 months. According to the difference of C_2-7 Cobb angle between preoperative and the latest follow-up, patients were divided into the group with loss of lordosis(>5°) and group without loss of lordosis(≤5°). Univariate and multivariate logistic regression analysis were used to analyze the influence of cervical semispinous muscle atrophy on the loss of C_2-7 lordosis.

The follow-up time of 40 patients was 25.0±13.2 months (12-63 months). Among them, 13 patients were divided into the group with loss of cervical lordosis, and 24 patients were divided into the group with non-loss of cervical lordosis. C_2-7 cervical semispinous muscle atrophy rate was (44.8±10.6)% (15.6%-62.8%). The univariate logistic regression analysis showed that the preoperative C_2-7 Cobb angle of >15° and the cervical semispinous muscle atrophy rate of >50% were related to the loss of cervical lordosis (both P<0.05). Multivariate logistic regression analysis indicated that preoperative C_2-7 Cobb angle of >15°( OR=82.797, 95%CI: 1.904-3 601.334, P=0.022) and postoperative cervical spine muscle atrophy rate of >50% ( OR=30.42, 95%CI: 2.126-435.463, P=0.012) were risk factors for cervical lordosis loss.

The loss of cervical lordosis following laminae recapping is significantly related to cervical semispinous muscle atrophy.

To investigate the role of balloon guided catheter (BGC) proximal blood flow control technique in mechanical thrombectomy for acute ischemic stroke with anterior circulation large artery occlusion.

Sixty-two patients with acute ischemic stroke with anterior circulation large artery occlusion who underwent mechanical thrombectomy from January 2018 to December 2019 at Department of Cerebrovascular Diseases, Zhengzhou University People′s Hospital, Department of Neurological Diseases, Nanyang Central Hospital and Department of Neurological Disease, Zhengzhou Central Hospital Affiliated to Zhengzhou University were enrolled into this study. BGC proximal blood flow control technique was used during operation of all cases. Among them, there were 36 cases of internal carotid occlusion combined with middle cerebral artery occlusion and 26 cases of middle cerebral artery occlusion in the horizontal segment.Duration of operation, recanalization of blood vessels [based on thrombolysis in cerebral infarction (TICI) score], surgical complications, and modified Rankin scale (mRS) at 90 days post operation were retrospectively analyzed.

The median duration of operation of 62 patients was 94.0 min (P₂₅: 53.0 min, P₇₅: 129.3 min). Successful recanalization (TICI 2b~3 grade) was achieved in 57 cases (91.9%) and failure was reported in 5 cases (8.1%). There were 47 cases (65.8%) with thrombus removal ≤ 2 times, of which 22 cases (35.5%) were successful in 1 thrombus removal. Thirty-two patients (51.6%) underwent stenting after embolization. Complications occurred in 17 cases (27.4%), including 7 cases (11.3%) of intraoperative thromboembolic events and 10 cases (16.1%) of symptomatic cerebral hemorrhage after operation, and 8 cases (12.9%) died. Among 62 cases, 37 (59.7%) had a good outcome (≤2 score) within 90 days after surgery, and 25 cases (40.3%) had a poor outcome.

Mechanical thrombectomy in the treatment of acute anterior circulation large artery occlusive cerebral infarction using BGC proximal blood flow control technology seems to be associated with short operative duration, high rates of blood vessel recanalization and that post single procedure, low incidence of thromboembolic events, and the proportion of good outcomes at 90 d post operation.

To preliminarily discuss the characteristics of elderly patients with traumatic brain injury (TBI) in China and to provide a reference for clinical treatment.

The clinical data of a total of 13 627 TBI patients collected from 56 hospitals in 22 provinces (cities) in the Chinese registry of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) from December 2014 to August 2017 were retrospectively analyzed. The baseline data, clinical manifestations, treatment measures, outcome, cause and location of injury of 3 694 TBI patients aged 60 years or older were extracted. The American Society of Anesthesiologists Physical Status Classification (ASA-PS) was used to evaluate the pre-injury health status, and the Injury Severity Score (ISS) and Glasgow Coma Score (GCS) were used to evaluate the patient’s injury.

Elderly TBI patients ≥60 years old accounted for 27.1% (3 694/13 627) of all TBI patients in the CENTER-TBI Chinese Registry. Among them, patients 60 to 74 years old accounted for 74.7% (2 760/3 694); 67.1% (2 478/ 3 694) were male patients. Patients with ASA-PS of grade I and II before injury accounted for 89.6% (3 309/3 694). The median (upper and lower quartiles) of ISS was 16 (10, 24) points. Patients with GCS 13-15 points accounted for 57.4% (2 120/3 694). Among them, 21.1% (779/3 694) of the patients underwent surgical treatment, and 11.1% (409/3 694) underwent intracranial pressure monitoring. 92.7% (3 426/3 694) were improved and discharged, and 7.3% (268/3 694) of the patients died. Among the causes of injury, traffic injuries accounted for 46.7% (1 726/3 694), and fall injuries accounted for 27.2% (1 005/3 694). The differences in the proportions of the two causes in different age groups were statistically significant (both P<0.001 ). Among the injured locations, traffic roads accounted for 53.3% (1 970/3 694), and homes accounted for 32.4% (1 196/3 694). The differences in the proportions of the two locations in different age groups were statistically significant (bothP<0.001).

The proportion of elderly patients with TBI in China is relatively high, who are mainly 60-74 years old and more commonly males. Most of the patients are in good health before injury and have mild TBI. The main causes and locations of elderly TBI injuries are traffic injuries and traffic roads.

To explore the role of controlled decompression in unilateral craniotomy for contrecoup traumatic brain injury.

The clinical data of 160 patients with contrecoup traumatic brain injury who underwent unilateral craniotomy at Department of Neurosurgery, the 904^th Hospital of Chinese PLA Joint Services from January 2016 to December 2018 were retrospectively analyzed. Among them, 80 patients underwent the surgery of controlled decompression (controlled decompression group), and the other 80 cases were treated with conventional decompression (conventional surgery group). There were no statistically significant differences in gender, age, cause of injury, preoperative pupil size, Glasgow Coma Score (GCS), the stress position, the time from injury to operation between the two groups of patients (all P>0.05). For the two groups of patients, we retrospectively analyzed their operation time, the incidence of intraoperative encephalocele, the postoperative incidences of delayed cerebral hemorrhage, reoperation of distant parts, cerebral infarction, epilepsy and hydrocephalus, and their difference in the Glasgow Outcome Score (GOS) at 6-month follow-up.

There was no significant difference in the operation time, or postoperative incidences of delayed hemorrhage, epilepsy and hydrocephalus between the two groups (all P>0.05). However, compared with conventional surgery group, the controlled decompression group had lower incidences of intraoperative encephalocele [13% (10/80)vs. 33% (26/80)], reoperation on remote site [16% (13/80) vs. 30% (24/80)] and cerebral infarction [24% (9/80) vs. 41% (33/80)] (all P<0.05). At 6-month follow-up, the controlled decompression group had higher proportion of favored outcomes [35% (28/80)vs. 20% (16/80)] and lower mortality [10% (8/80) vs. 24% (19/80)] compared with the conventional surgery group (both P<0.05).

For the treatment of contrecoup traumatic brain injury, unilateral craniotomy with the assistance of controlled decompression technology could reduce the incidences of some intraoperative and postoperative complications and improve the outcomes of patients.

To investigate the expression and biological function of long non-coding RNA Homeobox gene A11 antisense RNA(HOXA11-AS) in gliomas.

We first analyzed the expression of HOXA11-AS in the low-grade glioma and glioblastoma in The Cancer Genome Atlas (TCGA) database (689 cases) and normal brain tissue samples from the GTEx database (255 cases). Based on the TCGA database, we further analyzed the expression of HOXA11-AS in World Health Organization (WHO) grade Ⅱ to Ⅳ glioma samples. According to the median of HOXA11-AS expression, the testees were divided into high expression group and low expression group, and Kaplan-Meier survival curve was drawn. Log-rank test was used to compare the survival of glioma patients in the HOXA11-AS low expression group with that in the HOXA11-AS high expression group. Human astrocytes were set as the control group and real-time fluorescence quantitative polymerase-linked chain reaction (qRT-PCR) was performed in further in vitro experiments to assess the expression of HOXA11-AS in glioma U251, U87 and LN229 cell lines. In U87 and LN229 cell lines, overexpressed lentiviral vectors carrying the HOXA11-AS cDNA sequence were used to construct cell lines overexpressing HOXA11-AS. Construction of control cell lines was made with lentiviral vector. U87 and LN229 cell lines were transfected with siRNA to knock down the expression of HOXA11-AS. We then further studied the effects of HOXA11-AS on the proliferation, migration and invasion ability of glioma cells through EdU experiment, cell scratch experiment and Transwell experiment.

The difference in HOXA11-AS expression among normal brain tissue, low-grade glioma and glioblastoma was statistically significant (P<0.001). In the TCGA database, theHOXA11-AS expression levels of WHO grade Ⅲ and Ⅳ gliomas were higher than that of grade Ⅱ gliomas (P<0.001). Among glioma (all grades) patients, the overall survival of theHOXA11-AS high expression group (n=344) was shorter than that of the low expression group (n=345, P<0.001). In further in vitro experiments, the qRT-PCR test results showed that the expression ofHOXA11-AS in the U87 group, LN229 group and U251 group was increased compared with the control group (all P<0.001). The expression ofHOXA11-AS in the U87 and LN229 overexpression groups was up-regulated compared with the control group (both P<0.001). The expression ofHOXA11-AS in U87 knockdown groups and LN229 knockdown groups were all down-regulated compared with the control group (all P<0.001). The EdU experiment results showed that the EdU positive rates of U87 and LN229 overexpression groups were higher than those of U87 and LN229 control groups (allP<0.05). On the contrary, the EdU positive rates of U87 knockdown groups were lower than that of U87 nonsense sequence group, and the EdU positive rates of LN229 knockdown groups were lower than that of LN229 nonsense sequence group (allP<0.001). The results of cell scratch experiments showed that the cell migration rates of U87 and LN229 overexpression groups were higher than those of U87 and LN229 control groups (allP<0.05). On the contrary, the cell migration rates of U87 knockdown groups were lower than that of U87 nonsense sequence; compared with the LN229 nonsense sequence group, the cell migration rates of LN229 knockdown groups were both decreased (P<0.001). The results of the Transwell experiment showed that the numbers of gel-penetrating cells in the U87 and LN229 overexpression groups was higher than those in the U87 control group and the LN229 control group (allP<0.05). On the contrary, the numbers of gel-penetrating cells in U87 knockdown groups were lower than that of U87 nonsense sequence group (allP<0.05); the number of gel-penetrating cells in LN229 knockdown groups were lower than that of LN229 nonsense sequence group(allP<0.05).

HOXA11-AS is highly expressed in brain gliomas and can promote the proliferation, migration and invasion of glioma cells.

To study the expression and clinical significance of TNFAIP6 in gliomas, and to determine its biological processes involved in the development and progression of gliomas.

The mRNA sequencing data and clinical data in the Chinese Glioma Genome Atlas (CGGA, n=309) were retrospectively analyzed, and mRNA sequencing data in The Cancer Genome Atlas (TCGA, n=550) were used for validation. The expression of TNFAIP6 in gliomas with different grades and molecular subtypes were analyzed by R software, and immunohistochemistry was used to verify the expression of TNFAIP6 in gliomas with different grades. Kaplan-Meier method and Cox regression model were used to evaluate the correlation between TNFAIP6 expression and prognosis of glioma. Pearson correlation coefficient was used to analyze the correlation between expression of TNFAIP6 and other genes. Gene ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functions of genes related to TNFAIP6.

In the CGGA and TCGA databases were analyzed, the TNFAIP6 expression was significantly increased in the WHO grade Ⅳ gliomas (all P<0.01). Immunohistochemical staining revealed the results that were consistent with the results above (P<0.01). TheTNFAIP6 expression in the isocitrate dehydrogenase (IDH) wildtype gliomas with different degrees was higher than that in IDH-mutant gliomas with different degrees (all P<0.01). In addition,TNFAIP6 expression in classical and mesenchymal types was higher than that in proneural and neural subtypes (all P<0.01);TNFAIP6 expression in patients with O6-methylguanine methyl transferase (MGMT) promoter methylation was higher than that in non-methylated group (all P<0.01). Patients with high expression ofTNFAIP6 had significantly shorter overall survival (OS) than those with low-expression of TNFAIP6 (all P<0.001). Multivariate Cox regression analysis showed that pathological grade (HR=2.371, 95%CI: 1.686-3.335)、radiotherapy (HR=0.431, 95%CI: 0.286-0.651) and were TNFAIP6 expression level (HR=1.305, 95%CI: 1.041-1.636) independently associated with OS of glioma patients (all P<0.05). There were 1 064 and 1 954 genes positively correlated withTNFAIP6 expression in CGGA and TCGA databases, respectively(r≥0.5, P<0.01). Bioinformatics analysis showed that the functions of genes positively related toTNFAIP6 were mainly enriched in extracellular matrix organization, angiogenesis, cell adhesion, inflammatory response, and so on.

With the increase of pathological grade of glioma, the expression level of TNFAIP6 increases gradually. TNFAIP6 is mainly involved in biological processes such as extravascular matrix composition, angiogenesis, cell adhesion and inflammatory response, which can predict the prognosis of glioma patients and provide a potential research and therapeutic target.

To analyze the expression characteristics and clinical significance of hematopoietic cell specific protein-1 (HCLS1) gene in gliomas.

Two mRNA sequencing datasets and clinical data were collected from the Chinese Glioma Genome Atlas (CGGA) (325 cases in the CGGA325 dataset, 693 cases in the CGGA693 dataset). The expression characteristics of HCLS1 were analyzed in different World Health Organization (WHO) pathological grades, isocitrate dehydrogenase (IDH) mutation status, 2016 central nervous system tumor classification, O⁶-methylguanine DNA methyltransferase (MGMT) promoter status. Using the median HCLS1 expression level as a cutoff, patients were divided into high and low expression groups. Kaplan-Meier survival analysis and log-rank test were used to compare the survival significance between stratified groups. Univariate and multivariate Cox regression analysis were used to assess prognostic factors for overall survival of patients with glioma. Glioma samples and survival information were collected from glioma patients admitted to Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from January 2007 to October 2015 (27 cases in group 1 and 17 cases in group 2). Quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) was used to detect the expression of HCLS1 in group 1. Immunohistochemical staining was used to detect the expression of HCLS1 protein in group 2, and Immunohistochemical staining scores were calculated. Bioinformatics methods were used to analyze the biological functions of HCLS1.

In the CGGA325 dataset, the expression of HCLS1 increased along with grade progression (F=30.29, P<0.001); the expression level ofHCLS1 in the IDH wildtype group was significantly higher than that in the IDH mutant group (t=8.51, P<0.001). In the 2016 classification of central nervous system tumors,HCLS1 expression was the lowest in lower grade gliomas with IDH mutation and 1p/19q codeletion among three lower grade groups (F=23.61, P<0.001), whileHCLS1 expression was higher in high grade gliomas with IDH wildtype (P<0.001); the expression ofHCLS1 was higher in the MGMT promoter unmethylated group (P=0.001). Patients who had higher HCLS1 expression had a significantly shorter survival time than those who had lower HCLS1 expression (P<0.001). Similar results were shown in the CGGA693 dataset. Multivariate Cox regression analysis showed that the expression ofHCLS1 was an independent hazard factor affecting the overall survival of patients with glioma (HR=1.951, 95%CI: 1.307-2.910, P=0.001). The results of qRT-PCR confirmed that the expression of HCLS1 increased along with grade progression (F=11.11, P<0.001). Immunohistochemical staining results showed that the scores ofHCLS1 protein in WHO Ⅱ-Ⅳ grade samples were 1.33±0.21, 3.40±0.87, 7.67±0.88, and the difference among groups was statistically significant (F=21.88, P<0.001). The overall survival of patients with high HCLS1 gene and protein expression were shorter than that of patients with low HCLS1 gene and protein expression in group 1 and 2 (bothP<0.05).HCLS1 might be related to the immune response of glioma cells based on the bioinformatics analysis.

The expression level of HCLS1 is related to the malignant degree of glioma and the survival of the patient, and can be used as a potential indicator for judging the prognosis of the patient.