High Expression of KIFC1 in Glioma Correlates with Poor Prognosis.

OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review.

BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival. AIM: To investigate the clinical features and survival factors in Chinese patients with PMME. METHODS: The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival. RESULTS: A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME. CONCLUSION: The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

Identification of a seven-cell cycle signature predicting overall survival for gastric cancer.

While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.

Coexistence of Pituitary Adenoma and Primary Pituitary Lymphoma: A Case Report and Review of the Literature.

In the pituitary sella, the coexistence of pituitary adenoma and primary pituitary lymphoma is exceedingly rare. Thus far, only six cases have been reported. Here, we present the seventh case of coexisting pituitary adenoma and primary pituitary lymphoma, which was difficult to differentiate from other sellar tumors. To our knowledge, this is the first case of the prolactin subtype of the pituitary adenoma in literature. We have also systematically reviewed the literature and summarized the characteristics of coexisting pituitary adenoma and lymphoma. We believe this report provides a new clinical reference for the diagnosis and treatment of collision tumors of pituitary adenoma and lymphoma.

DCLK1 inhibition attenuates tumorigenesis and improves chemosensitivity in esophageal squamous cell carcinoma by inhibiting ß-catenin/c-Myc signaling.

Doublecortin-like kinase 1 (DCLK1) is involved in tumorigenesis, tumor growth and metastasis, and epithelial-to-mesenchymal transition in many digestive tract tumors. It is reportedly highly expressed in Barrett's esophagus and esophageal adenocarcinoma, but its effects on the occurrence and progression of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin-treated cells. Western blot assay revealed that expression of nuclear ß-catenin and c-Myc was significantly increased in ESCC tissues and that si-DCLK1 markedly downregulated nuclear ß-catenin and c-Myc in Eca109 cells. Treatment with lithium chloride, an activator of ß-catenin signaling, partially abolished the si-DCLK1-induced inhibition of proliferation, migration, invasion, and chemoresistance of ESCC cells. These findings suggest that knockdown of DCLK1 may inhibit the progression of ESCC by regulating proliferation, migration, invasion, and chemosensitivity via suppressing the ß-catenin/c-Myc pathway, supporting a promising therapeutic target against ESCC.

Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway.

Malignant glioma is an aggressive type of brain tumor with poor prognosis and mostly incurable. Although cisplatin is used for adjuvant chemotherapy against glioma, intrinsic and acquired resistance restricts the application of cisplatin. Long noncoding RNA (lncRNA) DANCR is reported to regulate the differentiation and progression of several cancers. However, whether DANCR participates in cisplatin resistance of glioma is still unknown. In this study, we found that DANCR expression was negatively correlated with cisplatin sensitivity in glioma cells. Gain-of and loss-of function assays revealed that DNACR attenuated cisplatin-induced cell proliferation inhibition in vitro and xenograft growth suppression in vivo. Furthermore, DNACR also attenuated cisplatin-induced cell apoptosis in vitro and in vivo. Mechanistically, we found that DANCR upregulated AXL via competitively binding miR-33a-5p, miR-33b-5p, miR-1-3p, miR-206, and miR-613. Through upregulating AXL, DANCR activated PI3K/Akt/NF-κB signaling pathway in glioma cells. Inhibiting AXL/PI3K/Akt/NF-κB signaling pathway reversed the effects of DANCR on cisplatin resistance. In conclusion, we identified a cisplatin-resistance associated lncRNA DANCR. DANCR promotes cisplatin resistance via activating AXL/PI3K/Akt/NF-κB signaling pathway in glioma. Our data suggested that DANCR would be a potential biomarker for predicting cisplatin sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.

Association of genotypes of rs671 withinALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high- and low-incidence areas.

OBJECTIVE: : This study aimed to determine if gastric cardia adenocarcinoma (GCA) risk was associated with the lys (A or *2) allele at the rs671 (glu504lys) polymorphism within the aldehyde dehydrogenase 2 (ALDH2) gene in a Chinese Han population. We also aimed to investigateALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma (ESCC). METHODS: : We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and low-incidence areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used to genotype the rs671 polymorphism.χ2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA, and multivariate ordinal logistic regression was used to analyzeALDH2 genotypic distributions among different groups. RESULTS: : Compared withALDH2*1/*1 homozygotes,ALDH2*1/*2 andALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population (P>0.05). Interestingly, the ratio of homozygous or heterozygousALDH2 *2 carriers in high-incidence areas for both GCA and ESCC was lower than that in low-incidence areas (P<0.001). CONCLUSIONS: : Genotypes of rs671 atALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, theALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Truth telling for patients with esophageal squamous cell carcinoma in Henan, China.

OBJECTIVE: : This study aims to investigate the truth-telling status and the relevant factors of esophageal squamous cell carcinoma (ESCC) patients in Henan, China. METHODS: : A cross-sectional study from April to June 2015 using questionnaires was given to 301 family members of hospitalized ESCC patients based in three affiliated hospitals of Zhengzhou University (i.e., The First Hospital, The Second Hospital, and Tumor Hospital) and Anyang Tumor Hospital. RESULTS: : Among the 41.9% (126/301) hospitalized ESCC patients who knew of their true diagnoses, only 4.0% patients were informed by their corresponding responsible doctors, 39.7% by their family members, and 56.3% by themselves. Univariate analyses showed that disclosure of confirmed ESCC diagnosis to patients was correlated with gender, family history of cancer (FHC), education level, vocation, hospital administrative level, and attitudes of family members (P < 0.05). Furthermore, multivariate analysis indicated that attitude of family members was the most important and an independent factor for diagnosis disclosure. Those patients with a negative FHC, under-education, manual occupation, advanced stages, and hospitalized in municipal hospitals exhibited a low rate of truth telling. CONCLUSIONS: : Truth telling for ESCC patients in Henan is not prevalent and may be improved through consultation with family members, particularly for patients with a negative FHC, poor education, manual occupation, and advanced stages.

Golgi Phosphoprotein 3 Inhibits the Apoptosis of Human Glioma Cells in Part by Downregulating N-myc Downstream Regulated Gene 1.

BACKGROUND Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. Our previous study showed that GOLPH3 expression in glioma tissues was related to the severity of the malignancy of the cancer. However, the mechanism by which GOLPH3 affects cell apoptosis is largely unknown. The present study was designed to explore the possible mechanism of GOLPH3 in cell apoptosis. MATERIAL AND METHODS To analyze the biological role of GOLPH3 in glioma cells, we used GOLPH3 small interference RNA in apoptosis of glioma cells. The apoptosis of glioma cells was detected by flow cytometry. The expression level of GOLPH3 and NDRG1 protein was determined by Western blot analyses and immunohistochemical staining, respectively, to evaluate their association with glioma. Tumor tissues were collected from patients with glioma. Normal cerebral tissues were acquired from cerebral trauma patients undergoing internal decompression surgery. RESULTS We confirm that the decrease of GOLPH3 that promotes the apoptosis of glioma cells may be regulated by the activation of NDRG1 and cleaved capcase 3. There was a inverse association between GOLPH3 and NDRG1 in glioma samples. CONCLUSIONS Our findings indicate that GOLPH3 and NDRG1 both play an important role in glioma etiology. Either GOLPH3 or NDRG1 might be a potential candidate for malignant glioma therapy.

Protein phosphatase 4 catalytic subunit is overexpressed in glioma and promotes glioma cell proliferation and invasion.

Protein phosphatase 4 catalytic subunit (PP4C) has been identified to be overexpressed in various solid cancers. However, to date, the role of PP4C in glioma remains elusive. In the present study, we aimed to detect PP4C expression in glioma patients and explore its function in glioma and prognostic significance in patients with glioma. The expression levels of PP4C mRNA and protein in 30 glioma tissue specimens and 10 non-cancerous brain tissue specimens were detected by qRT-PCR and Western blot analysis. Moreover, immunohistochemistry was performed to assess PP4C expression in 120 glioma patients. The effects of siRNA-mediated PP4C silencing on the proliferation, migration, and invasion of U251 and U87 glioma cells were assessed. We found that PP4C was upregulated in glioma tissue at both mRNA and protein levels compared with non-cancerous brain tissue. Univariate and multivariate analyses indicated that high PP4C expression was an independent prognostic factor for poor survival of glioma patients. Knockdown of PP4C reduced the proliferation, migration, and invasion of U251 and U87 cells. In conclusion, our findings suggest that PP4C plays an oncogenic role in glioma development and progression and might serve as a prognostic biomarker as well as a potential therapeutic target for glioma.

Expression and clinical significance of nestin in astrocytic tumors.

PURPOSE: This study aimed to investigate the expression and clinical significance of nestin in human astrocytic tumors. METHODS: Indirect immunofluorescent staining and flow cytometry were used to quantitatively detect the nestin content in 35 specimens, including 3 normal brain tissues, 29 astrocytic tumor (AT) tissues, and 3 peritumoral tissues. RESULTS: In normal brain tissues, nestin expression was extremely low. Nestin expression was significantly positively correlated with the histological grade of astrocytic tumors (p<0.05, rs=0.83). Nestin content in the peritumoral tissues was between the levels of nestin in tumor tissue and in normal brain tissue (p<0.01). Nestin expression was unrelated to the patient's gender, age, tumor location, size, etc. (p>0.05). CONCLUSION: The application of flow cytometry in the determination of nestin content could improve the accuracy of early cancer diagnosis. This method would be helpful for developing a reference range that is closely related to the pathological grading of ATs through routine assessments of nestin in many patients. Additionally, through examining nestin levels in peritumoral tissues, the invasiveness of ATs can be clarified.

Expression of the Golgi phosphoprotein-3 gene in human gliomas: a pilot study.

The oncogene Golgi phosphoprotein 3 (GOLPH3) has been found in several solid cancers, but its expression in glioma tumor tissues is unknown. Reverse transcription polymerase chain reaction and Western blot was used to investigate expression of GOLPH3 mRNA and protein, respectively, in 76 patients with glioma. Non-cancerous brain issues and lung cancer cells were used as controls. There were 45 males and 31 females (mean age 50.7 ± 12.8 years). Astrocytoma was found in 65 patients and glioblastoma in 11. No GOLPH3 expression was found in the non-cancerous brain tissues, but positive GOLPH3 protein was found in lung cancer cells. GOLPH3 mRNA and protein expression were identified in 40 patients with glioma (52.6%). Positive expression of GOLPH3 mRNA or protein was similar in patients with astrocytoma grades I-III and glioblastoma (P > 0.05). The highest mean value of GOLPH3 mRNA and protein was found in patients with glioblastoma (P < 0.01) whereas the lowest mean values were found in those with grade I astrocytoma (P < 0.01). We concluded that, in this pilot study, GOLPH3 expression was present in more than half of the patients with glioma. The amount of GOLPH3 expression in the glioma was associated with the severity of the tumor. Whether positive GOLPH3 gene expression can be used as a predictor for prognosis of the patients or as a therapeutic target for glioma requires further investigation.

Association between AKT/mTOR signalling pathway and malignancy grade of human gliomas.

The mammalian target of rapamycin (mTOR) signaling pathway has emerged as a major effector of cell growth and proliferation, and is an attractive target for cancer therapy. However, the association between mTOR pathway and the malignancy grade of human gliomas has not been thoroughly investigated. Tumor tissues from 87 Chinese patients (49 males, average age of 51.7 ± 13.0 years, range 15-78) with glioma were prospectively collected. The expression of three key proteins of the mTOR pathway, pAKT, pmTOR and p-p70S6 kinase (p-p70S6K) was measured by semi-quantitative immunohistochemical techniques. Grade I-II, III and IV glioma was pathologically identified in 27 (31.0%), 24 (27.6%) and 36 (41.4%) patients, respectively. Of the 87 patients, pAKT, pmTOR and p-p70S6K were found in 63 (72.4%), 65 (74.7%), and 63 (72.4%) patients, respectively. The expression of all three pAKT, pmTOR and p-p70S6K proteins was found in 42 (48.3%) patients, while only one or two of the three proteins were found in the remaining patients (51.7%). The percentage of patients with very strong expression of pAKT, pmTOR and p-p70S6K in grade IV glioma was 13 (36.1%), 16 (44.4%) and 15 (41.7%), respectively, which was greater than in grade I or II tumors (0-3.7%, P < 0.01). In conclusion, expression of mTOR pathway proteins pAKT, pmTOR and p-p70S6K can be found in human glioma of all malignancy grades. However, higher levels of these proteins were associated with advanced malignancy grades of the tumor.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

[Clinical study of cerebral oxygen utilization coefficients in patients with severe head injury].

OBJECTIVE: To investigate the relationship in cerebral oxygen utilization coefficients (O.2UCc) in patients with acute severe head injury and illness prognosis. METHODS: Forty patients with acute severe head injury were studied, and 40 patients with light head injury were used as control. Through blood analysis, the changes in oxygen saturation of carotid blood (SaO(2)), oxygen saturation of jugular blood (SjO(2)), cerebral arteriovenous difference of oxygen saturation (S(a-j)O(2)), O.2 UCc were observed. Furthermore, the relationship of these patients' condition and prognosis was analyzed. RESULTS: There was no significant change between the test group and control group in SaO(2). In test group, SjO(2) increased and O.2 UCc decreased, there was an obvious difference between two groups (both P<0.01). In test group, 26 died and 14 lived. There was no significant difference between died and lived patients in SaO(2). SjO(2) significantly increased and O.2 UCc obviously decreased in died patients in comparison with those of the lived patients (both P<0.01). CONCLUSION: Cerebral oxygen metabolism dynamics obstacle frequently was accompanied with acute severe head injury. The high SjO(2) and low O.2 UCc are main symptoms with O.2 UCc<11percent hinting a bad prognosis.