Comprehensive Analysis on Prognostic Signature Based on T Cell-Mediated Tumor Killing Related Genes in Gastric Cancer.

Although immunotherapy is a valuable treatment for gastric cancer (GC), identifying the patients who would benefit most from this approach presents a challenge. In this study, GC patients were divided into two subtypes by consensus clustering according to T cell-mediated tumor killing related genes (TTKRGs), and there were significant differences in tumor-infiltrating immune cells, signaling pathways, and gene expression of immunomodulators and inhibitory immune checkpoints between the two subtypes. Then, we developed an individualized signature based on TTKRGs, and its clinical and predictive value in GC patients for chemotherapeutic and immunotherapeutic responses was assessed. We confirmed the expression levels of signature genes in GC tumor tissue using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, to improve the accuracy of GC prognosis predictions, we established a nomogram. We further identified some compounds as sensitive drugs targeting GC risk groups. The signature showed significant predictive ability across RNA-seq, microarray, and qRT-PCR cohorts, which could assist in predicting survival, immunotherapeutic and chemotherapeutic outcomes in GC patients.

Recent molecular design strategies for efficient photodynamic therapy and its synergistic therapy based on AIE photosensitizers.

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer.

Purpose: Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal EPHA5 methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the EPHA5 methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis. Methods: A total of 366 GC cases and 374 controls were selected as the subjects of this study to collect their environmental factors, and the EPHA5 methylation status was detected through the methylation-sensitive high-resolution melting method. Logistic regression analysis was utilized to evaluate the associations among EPHA5 methylation, environmental factors and GC risk. Meanwhile, the propensity score (PS) was used to adjust the imbalance of some independent variables. Results: After PS adjustment, EPHA5 Pm (positive methylation) was more likely to increase the GC risk than EPHA5 Nm (negative methylation) (ORb = 1.827, 95% CI [1.202-2.777], P = 0.005). EPHA5 Pm had a more significant association with GC risk in the elderly (ORa = 2.785, 95% CI [1.563-4.961], P = 0.001) and H. pylori-negative groups (ORa = 2.758, 95% CI [1.369-5.555], P = 0.005). Moreover, the combined effects of EPHA5 Pm and H. pylori infection (ORc a = 3.543, 95% CI [2.233-5.621], P < 0.001), consumption of alcohol (ORc a = 2.893, 95% CI [1.844-4.539], P < 0.001), and salty food intake (ORc a = 4.018, 95% CI [2.538-6.362], P < 0.001) on increasing the GC risk were observed. In addition, no convincing association was found between EPHA5 Pm and the GC prognosis. Conclusions: EPHA5 methylation in PBLs and its combined effects with environmental risk factors are related to the GC risk.

Risk and Prognosis of Second Primary Cancers among Ovarian Cancer Patients, Based on SEER Database.

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004-2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding.

Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer.

Background: Tumor microenvironment (TME) has been reported to have a strong association with tumor progression and therapeutic outcome, and epigenetic modifications such as DNA methylation can affect TMB and play an indispensable role in tumorigenesis. However, the potential mechanisms of TME and DNA methylation remain unclear in cervical cancer (CC). Methods: The immune and stromal scores of TME were generated by the ESTIMATE algorithm for CC patients in The Cancer Genome Atlas (TCGA) database. The TME and DNA methylation-related genes were identified by the integrative analysis of DNA promoter methylation and gene expression. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed 1,000 times to further identify a nine-gene TME and DNA methylation-related prognostic signature. The signature was further validated in Gene Expression Omnibus (GEO) dataset. Then, the identified signature was integrated with the Federation International of Gynecology and Obstetrics (FIGO) stage to establish a composite prognostic nomogram. Results: CC patients with high immunity levels have better survival than those with low immunity levels. Both in the training and validation datasets, the risk score of the signature was an independent prognosis factor. The composite nomogram showed higher accuracy of prognosis and greater net benefits than the FIGO stage and the signature. The high-risk group had a significantly higher fraction of genome altered than the low-risk group. Eleven genes were significantly different in mutation frequencies between the high- and low-risk groups. Interestingly, patients with mutant TTN had better overall survival (OS) than those with wild type. Patients in the low-risk group had significantly higher tumor mutational burden (TMB) than those in the high-risk group. Taken together, the results of TMB, immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) score suggested that patients in the low-risk group may have greater immunotherapy benefits. Finally, four drugs (panobinostat, lenvatinib, everolimus, and temsirolimus) were found to have potential therapeutic implications for patients with a high-risk score. Conclusions: Our findings highlight that the TME and DNA methylation-related prognostic signature can accurately predict the prognosis of CC and may be important for stratified management of patients and precision targeted therapy.

Comprehensive Analysis of an Individualized Immune-Related lncRNA Pair Signature in Gastric Cancer.

Long noncoding RNAs (lncRNAs) have diverse functions, including immune regulation. Increasing studies have reported immune-related lncRNAs in the prognosis of multiple cancers. In this study, we developed an individualized signature containing 13 immune-related lncRNA pairs (IRLPs) which could predict the overall survival, disease-free survival, progression-free survival, and disease-specific survival of gastric cancer (GC) patients in The Cancer Genome Atlas (TCGA) cohort, and internal and external validations, signature comparisons, and subgroup analyses further confirmed its superiority, stability, and generalizability. Notably, this signature also showed good applicability in discriminating the prognosis of pan-cancer patients. Then, we constructed and validated a nomogram for overall survival based on the signature and clinical factors, which allowed more accurate predictions of GC prognosis. In addition, we revealed that the low survival rate of patients with high-risk scores may be due to their aggressive clinical features, enriched cancer-related signaling pathways, the infiltration of specific immunosuppressive cells, and low tumor mutation burden. We further predicted obviously worse immunotherapeutic responses in the high-risk groups and identified some candidate compounds targeting GC risk group differentiation. This signature based on the IRLPs may be promising for predicting the survival outcomes and immunotherapeutic responses of GC patients in clinical practice.