Prognostic significance of TMEM131L in glioma and establishment of oxidative stress prognostic model.

Gliomas are the most aggressive of all brain tumors. In this study, it was found that there is a significant expression of transmembrane-like 131 (TMEM131L) in glioma tissues. The relevance of TMEM131L in the diagnosis and clinical prognosis of GBM and LGG was verified by additional clinical correlation and survival analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve reflected the diagnostic effect of TMEM131L on the clinicopathologic features of glioma. As a unique molecular marker for the poor prognosis of overall survival (OS), PFI, and DSS in patients with GCB and LGG, TMEM131L might be employed, according to time-dependent ROC curves and Kaplan-Meier survival analysis at 1, 3, and 5 years. The potential methylation sites of TMEM131L were selected by correlation analysis between TMEM131L and DNA methylation sites. Meanwhile, TMEM131L was significantly correlated with matrix, immunity, and estimated scores of GBM and LGG. The CIBERSORT analysis revealed a significant correlation between immune checkpoint and infiltration of 22 different kinds of immune cells. Coexpression genes of TMEM131L associated with oxidative stress phenotype were screened by the LASSO logistic regression analysis. Nomogram and calibration curves further confirmed that the prognostic model composed of SYT1, CREB3L3, ITPR1, RASGRF2, PDX1, and RASGRF1 has good stability and potential application value for poor prognosis in patients with glioma.

Circular RNA circLRCH3 promotes oxaliplatin resistance in gastric cancer through the modulation of the miR-383-5p/FGF7 axis.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor of the digestive system. Circular RNAs (circRNAs) play a vital role in tumorigenesis and chemoresistance. The current study aimed to explore the possible role and mechanism of circRNA leucine rich repeats and calponin homology domain containing 3 (circLRCH3) in GC chemoresistance. METHODS: The levels of circLRCH3, microRNA-383-5p (miR-383-5p) and fibroblast growth factor 7 (FGF7) were determined by quantitative real-time PCR or Western blot. Cell Counting Kit-8 (CCK-8) assay was utilized to evaluate cell survival rate and proliferation ability. Colony formation, transwell and flow cytometry assays were used to assess cell proliferation, migration, invasion and apoptosis. The expression of multidrug resistance proteins was detected by Western blot. The binding relationship between miR-383-5p and circLRCH3/FGF7 was verified by dual-luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the role of circLRCH3 in OXA resistance in vivo. RESULTS: CircLRCH3 and FGF7 levels were up-regulated, while miR-383-5p level was reduced in OXA-resistant GC tissues and cells. Depletion of circLRCH3 attenuated the resistance of OXA-resistant cells to OXA. CircLRCH3 silence reduced OXA resistance by regulating miR-383-5p. Besides, miR-383-5p elevated OXA sensitivity of GC cells by repressing FGF7. Moreover, the deletion of circLRCH3 increased OXA sensitivity in vivo. CONCLUSIONS: Knockdown of circLRCH3 alleviated OXA resistance of GC by modulating the miR-383-5p/FGF7 axis, which provided a promising therapeutic target for GC chemoresistance.

Tumoral Overexpression of Hepcidin is Associated with Poor Prognosis of Patients with Clear Cell Renal Cell Carcinoma.

This study aimed to investigate the prognostic value of tumoral HAMP expression in patients with clear cell renal cell carcinoma (ccRCC). In a TCGA dataset, we found that HAMP mRNA expression was increased in ccRCC tumors compared with normal controls. Tumoral HAMP mRNA expression was positively correlated with clinical stage, tumor grade, and TNM stages. Patients with high HAMP expression had poorer overall survival than those with low HAMP expression. Tumoral HAMP mRNA level independently predicted the survival of patients. HAMP protein expression was increased in real-world ccRCC tumors compared with those in paired, adjacent noncancerous tissue and was positively correlates with tumor grading. These results suggest HAMP as a potential prognostic factor for ccRCC patients.

Application of Prognostic Models Based on Psoas Muscle Index, Stage, Pathological Grade, and Preoperative Carcinoembryonic Antigen Level in Stage II-III Colorectal Cancer Patients Undergoing Adjuvant Chemotherapy.

OBJECTIVE: To investigate the effect of sarcopenia on the prognosis of stage II-III colorectal cancer patients undergoing adjuvant chemotherapy. METHODS: A total of 196 stage II-III colorectal cancer patients who received 8 cycles of postoperative chemotherapy were retrospectively analyzed. An abdominal CT acquired at 3-4 weeks after surgery was used to calculate the psoas muscle index. Subsequently, once gender-specific receiver operating characteristic curves were plotted and cut-off values of psoas muscle index were defined, the clinicopathological characteristics and the prognosis of patients with high and low values were compared. Lastly, prognostic models were established based on the independent prognostic factors of relapse-free survival and overall survival identified by COX analysis. RESULTS: Based on the psoas muscle index, the prevalence of sarcopenia was 37.5% among 196 patients. This prevalence has significant correlation with patients' age and gender. However, it was not related to the AJCC stage, T stage, lymph node metastasis, pathological grade, grade III-IV myelosuppression, or preoperative carcinoembryonic antigen level. In addition, both the relapse-free and the overall survival of patients with low and high psoas muscle indexes were significantly different. COX analysis indicated that the psoas muscle index was an independent prognostic factor. Both the overall survival prognostic model based on patients' psoas muscle index, stage, pathological grade, and preoperative carcinoembryonic antigen level and the relapse-free survival prognostic model based on patients' psoas muscle index, pathological grade, and preoperative carcinoembryonic antigen level could accurately predict the prognosis of patients. CONCLUSION: For stage II-III colorectal cancer patients, the presence of sarcopenia before adjuvant chemotherapy would adversely affect their recurrence-free and overall survival. Prognostic models based on psoas muscle index, stage, pathological grade, and preoperative carcinoembryonic antigen level could accurately predict the prognosis in these patients.

Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis.

BACKGROUND: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. METHODS: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. RESULTS: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. CONCLUSIONS: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.