Pan-cancer analysis identifies proteasome 26S subunit, ATPase (PSMC) family genes, and related signatures associated with prognosis, immune profile, and therapeutic response in lung adenocarcinoma.

Background: Proteasome 26S subunit, ATPase gene (PSMC) family members play a critical role in regulating protein degradation and are essential for tumor development. However, little is known about the integrative function and prognostic significance of the PSMC gene family members in lung cancer. Methods: First, we assessed the expression and prognostic features of six PSMC family members in pan-cancer from The Cancer Genome Atlas (TCGA) dataset. Hence, by focusing on the relationship between PSMC genes and the prognostic, genomic, and tumor microenvironment features in lung adenocarcinoma (LUAD), a PSMC-based prognostic signature was established using consensus clustering and multiple machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO) Cox regression, CoxBoost, and survival random forest analysis in TCGA and GSE72094. We then validated it in three independent cohorts from GEO and estimated the correlation between risk score and clinical features: genomic features (alterations, tumor mutation burden, and copy number variants), immune profiles (immune score, TIDE score, tumor-infiltrated immune cells, and immune checkpoints), sensitivity to chemotherapy (GDSC, GSE42127, and GSE14814), and immunotherapy (IMvigor210, GSE63557, and immunophenoscore). Twenty-one patients with LUAD were included in our local cohort, and tumor samples were submitted for evaluation of risk gene and PD-L1 expression. Results: Nearly all six PSMC genes were overexpressed in pan-cancer tumor tissues; however, in LUAD alone, they were all significantly correlated with overall survival. Notably, they all shared a positive association with increased TMB, TIDE score, expression of immune checkpoints (CD276 and PVR), and more M1 macrophages but decreased B-cell abundance. A PSMC-based prognostic signature was established based on five hub genes derived from the differential expression clusters of PSMC genes, and it was used to dichotomize LUAD patients into high- and low-risk groups according to the median risk score. The area under the curve (AUC) values for predicting survival at 1, 3, and 5 years in the training cohorts were all >.71, and the predictive accuracy was also robust and stable in the GSE72094, GSE31210, and GSE13213 datasets. The risk score was significantly correlated with advanced tumor, lymph node, and neoplasm disease stages as an independent risk factor for LUAD. Furthermore, the risk score shared a similar genomic and immune feature as PSMC genes, and high-risk tumors exhibited significant genomic and chromosomal instability, a higher TIDE score but lower immune score, and a decreased abundance of B and CD8+ T cells. Finally, high-risk patients were suggested to be less sensitive to immunotherapy but had a higher possibility of responding to platinum-based chemotherapy. The LUAD samples from the local cohort supported the difference in the expression levels of these five hub genes between tumor and normal tissues and the correlation between the risk score and PD-L1 expression. Conclusion: Overall, our results provide deep insight into PSMC genes in LUAD, especially the prognostic effect and related immune profile that may predict therapeutic responses.

Clinical and biomechanical researches of polyetheretherketone (PEEK) rods for semi-rigid lumbar fusion: a systematic review.

Lumbar spinal fusion using rigid rods is a common surgical technique. However, adjacent segment disease and other adverse effects can occur. Dynamic stabilization devices preserve physiologic motion and reduce painful stress but have a high rate of construct failure and reoperation. Polyetheretherketone (PEEK) rods for semi-rigid fusions have a similar stiffness and adequate stabilization power compared with titanium rods, but with improved load sharing and reduced mechanical failure. The purpose of this paper is to review and evaluate the clinical and biomechanical performance of PEEK rods. A systematic review of clinical and biomechanical studies was conducted. A literature search using the PubMed, EMBASE, and Cochrane Library databases identified studies that met the eligibility criteria. Eight clinical studies and 15 biomechanical studies were included in this systematic review. The visual analog scale and the Oswestry disability index improved significantly in most studies, with satisfactory fusion rates. The occurrence of adjacent segment disease was low. In biomechanical studies, PEEK rods demonstrated a superior load-sharing distribution, a larger adjacent segment range of motion, and reduced stress at the rod-screw/screw-bone interfaces compared with titanium rods. The PEEK rod construct was simple to assemble and had a reliable in vivo performance compared with dynamic devices. The quality of clinical studies was low with confounding results, although results from mechanical studies were encouraging. There is no evidence strong enough to confirm better outcomes with PEEK rods than titanium rods. More studies with better protocols, a larger sample size, and a longer follow-up time are needed.

Prognostic value of EUS combined with MSCT in predicting the recurrence and metastasis of patients with gastric cancer.

OBJECTIVE: This study aims to explore the prognostic value of endoscopic ultrasonography combined with multi-slice spiral computed tomography in predicting the recurrence and metastasis of gastric cancer, as well as investigate the correlation of fragile histidine triad protein expression with the tumor-node-metastasis stage of gastric cancer patients. METHODS: A total of 81 gastric cancer patients were selected in our study. All patients were examined by endoscopic ultrasonography and multi-slice spiral computed tomography before operation, and gastric cancer tissues and adjacent normal tissues were obtained after operation. Immunohistochemistry was performed to detect fragile histidine triad expression. All patients were followed up for 3 years after operation. Univariate and multivariate analysis of risk factors were conducted for the prognosis of gastric cancer patients. RESULTS: Endoscopic ultrasonography combined with multi-slice spiral computed tomography could increase the accuracy of preoperative tumor-node-metastasis stage of gastric cancer patients. In gastric cancer tissues, fragile histidine triad expression was mostly weakly positive with a positive rate of 60.5%. In gastric cancer adjacent normal tissues, the positive fragile histidine triad expression was mostly moderate with a positive rate of 79.0%. The fragile histidine triad expression was negatively correlated with tumor-node-metastasis stage of gastric cancer patients. The fragile histidine triad expression decreased along with the increase of T-stage, N-stage and M-stage of gastric cancer patients. Univariate and multivariate analysis showed that T-stage and N-stage were risk factors for the recurrence/metastasis and 3-year mortality of gastric cancer patients, while fragile histidine triad expression was a protective factor. CONCLUSION: Our study demonstrated that endoscopic ultrasonography combined with multi-slice spiral computed tomography may be more accurate in assessing the preoperative tumor-node-metastasis stage of gastric cancer patients.