Establishment of an ovarian cancer exhausted CD8+T cells-related genes model by integrated analysis of scRNA-seq and bulk RNA-seq.

Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.

CD4+ conventional T cells-related genes signature is a prognostic indicator for ovarian cancer.

Introduction: It is believed that ovarian cancer (OC) is the most deadly form of gynecological cancer despite its infrequent occurrence, which makes it one of the most salient public health concerns. Clinical and preclinical studies have revealed that intratumoral CD4+ T cells possess cytotoxic capabilities and were capable of directly killing cancer cells. This study aimed to identify the CD4+ conventional T cells-related genes (CD4TGs) with respect to the prognosis in OC. Methods: We obtained the transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD4TGs were first identified from single-cell datasets, then univariate Cox regression was used to screen prognosis-related genes, LASSO was conducted to remove genes with coefficient zero, and multivariate Cox regression was used to calculate riskscore and to construct the CD4TGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), decision curve analysis (DCA), nomogram, and calibration were made to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. The role of riskscore has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy. A risk signature with 11 CD4TGs in OC was finally established in the TCGA database and furtherly validated in several GEO cohorts. Results: High riskscore was significantly associated with a poorer prognosis and proven to be an independent prognostic biomarker by multivariate Cox regression. The 1-, 3-, and 5-year ROC values, DCA curve, nomogram, and calibration results confirmed the excellent prediction power of this model. Compared with the reported risk models, our model showed better performance. The patients were grouped into high-risk and low-risk subgroups according to the riskscore by the median value. The low-risk group patients tended to exhibit a higher immune infiltration, immune-related gene expression and were more sensitive to immunotherapy and chemotherapy. Discussion: Collectively, our findings of the prognostic value of CD4TGs in prognosis and immune response, provided valuable insights into the molecular mechanisms and clinical management of OC.

Construction and validation of a histone acetylation-related lncRNA prognosis signature for ovarian cancer.

Ovarian cancer (OC) leads to the most deaths among gynecological malignancies. The various epigenetic regulatory mechanisms of histone acetylation in cancer have attracted increasing attention from scientists. Long non-coding RNA (lncRNA) also plays an important role in multiple biology processes linked to OC. This study aimed to identify the histone acetylation-related lncRNAs (HARlncRNAs) with respect to the prognosis in OC. We obtained the transcriptome data from Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA); HARlncRNAs were first identified by co-expression and differential expression analyses, and then univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) were used to construct the HARlncRNAs risk signature. Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analysis (GSEA) in risk groups were conducted to explore the tightly correlated pathways with the risk group. A risk signature with 14 HARlncRNAs in OC was finally established and further validated in the International Cancer Genome Consortium (ICGC) cohort; the 1-, 3-, and 5-year ROC value, nomogram, and calibration results confirmed the good prediction power of this model. The patients were grouped into high- and low-risk subgroups according to the risk score by the median value. The low-risk group patients exhibited a higher homologous recombination deficiency (HRD) score, LOH_frac_altered, and mutLoad_nonsilent. Furthermore, consensus clustering analysis was employed to divide OC patients into three clusters based on the expression of the 14 HARlncRNAs, which presented different survival probabilities. Principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) were also performed to evaluate the three clusters. In conclusion, the risk signature composed of 14 HARlncRNAs might function as biomarkers and prognostic indicators with respect to predicting the response to the anti-cancer drugs in OC.

Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules.

Background: Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis. Methods: SMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients' need to undergo whole-body PET/CT and brain MRI examination. Results: A total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted. Conclusion: For SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.

T Lymphocyte Infiltration in Association with IDO1 Expression in Resected Lung Adenocarcinoma and Normal Adjacent Lung Tissues.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step of tryptophan catabolism in the kynurenine (Kyn) pathway. IDO1 downregulates natural killer cell receptors, and by mechanism, tumor cells escape immune surveillance. METHODS: IDO1 protein and mRNA were assessed by immunohistochemistry, immunoblotting, and PCR in the 68 resected lung adenocarcinomas at stages I-III as well as adjacent normal lung tissues. Infiltration of CD3, CD8, and CD4 lymphocytes in the tumor and adjacent normal lung tissues was assessed by immunohistochemical staining. RESULTS: IDO1 protein and mRNA were detected in various stages of lung adenocarcinoma with highest expression at stage III. In contrast, biomarkers of T cell subset, CD3, CD4, and CD8, were highly expressed in the normal lung tissues and stage I adenocarcinoma tissues but significantly reduced in the stage II and III tumor tissues. CONCLUSIONS: The current study demonstrated that the higher level of IDO1 expression in the lung adenocarcinoma was, the less infiltration of T lymphocytes was found in the tumors. Findings of this study indicated that IDO1 may contribute to the reduction of T lymphocyte infiltration into the lung adenocarcinoma.

Debt-relief programs and money left on the table: Evidence from Canada's response to COVID-19.

This paper analyzes the effectiveness of debt-relief programs targeting short-run household liquidity constraints implemented in Canada in response to the COVID-19 pandemic. These programs allowed individuals to push off mortgage and credit card payments and cut in half interest rates on credit card debt. Using credit bureau data, we document that, despite potential savings above $4 billion, enrolment was limited: 24% for mortgages and 7% for credit cards. By exploiting the richness of our data set, we provide evidence that close to 80% of individuals were unaware of the credit card relief program while others faced important fixed non-monetary costs preventing uptake.

Nous analysons l'efficacité de mesures d'allégement financier aux emprunteurs mises en place par les institutions financières canadiennes durant la pandémie de COVID­19. Ces mesures offraient aux ménages l'occasion de repousser leurs paiements hypothècaires ou de cartes de crédit. À l'aide de données sur les comptes de crédit individuels, nous documentons que malgré le fait que ces programmes offraient des économies potentielles de plus de 4 milliards de dollars, les taux de recours ont été faibles: 24 % pour les prêts hypothécaires et 7 % pour les cartes de crédit. Nous montrons également que près de 80 % des individus n'étaient pas au courant du programme d'allègement pour les cartes de crédit alors que d'autres n'ont pas déposé de demande en raison de la présence de coûts non monétaires fixes.

Neuroimaging diagnosis of intraventricular Central neurocytoma.

OBJECTIVE: To study the CT and MRI imaging manifestations of central and intraventricular central neurocytoma in the ventricle. METHODS: In this paper, 39 patients with central nervous cell tumour treated in our hospital from August 2015 to June 2018 were selected. All patients were performed plain CT scans using GE Highspeed CT; GE signa Twin speed 1.5 T superconducting magnet Resonance scanners were used to perform MRI plain scans on all patients. Observe the specific location, size, and morphology of tumours in the supra- and sub-ventricular ventricles of 39 central nervous cell tumour patients, and compare the performance of CT examination with the performance of MRI examination. RESULTS: Of the 39 patients with central neurocytoma, 13 were in the right lateral ventricle, 9 were in the left lateral ventricle, 11 patients had tumours in both lateral ventricles, and 6 patients had bilateral ventricles and bilateral ventricles. There were tumours in the third ventricle; 39 patients had an average tumour size of 52 mm; 36 patients had irregular lobes, and 3 patients had blurred tumour boundaries; some tumours had different degrees of calcification. CONCLUSIONS: The location and characteristics of the imaging manifestations of central nervous cell tumours are typical. Both CT scans and MRI scans can effectively detect central neuroblastomas, and MRI imaging examinations can effectively improve the diagnosis accuracy of tumour is better than that of CT.