Comprehensive Analysis of Disulfidptosis-Related LncRNAs in Molecular Classification, Immune Microenvironment Characterization and Prognosis of Gastric Cancer.

BACKGROUND: Disulfidptosis is a novel form of programmed cell death that unveils promising avenues for the exploration of tumor treatment modalities. Gastric cancer (GC) is a malignant tumor characterized by high incidence and mortality rate. However, there has been no systematic study of disulfidptosis-related long noncoding RNAs (DRLs) signature in GC patients. METHODS: The lncRNA expression profiles containing 412 GC samples were acquired from the Cancer Genome Atlas (TCGA) database. Differential expression analysis was performed alongside Pearson correlation analysis to identify DRLs. Prognostically significant DRLs were further screened using univariate COX regression analysis. Subsequently, LASSO regression and multifactorial COX regression analyses were employed to establish a risk signature composed of DRLs that exhibit independent prognostic significance. The predictive value of this risk signature was further validated in a test cohort. The ESTIMATE, CIBERSORT and ssGSEA methodologies were utilized to investigate the tumor immune microenvironment of GC populations with different DRLs profiles. Finally, the correlation between DRLs and various GC drug responses was explored. RESULTS: We established a prognostic signature comprising 12 disulfidptosis-related lncRNAs (AC110491.1, AL355574.1, RHPN1-AS1, AOAH-IT1, AP001065.3, MEF2C-AS1, AC016394.2, LINC00705, LINC01952, PART1, TNFRSF10A-AS1, LINC01537). The Kaplan-Meier survival analysis revealed that patients in the high-risk group exhibited a poor prognosis. Both univariate and multivariate COX regression models demonstrated that the DRLs signature was an independent prognostic indicator in GC patients. Furthermore, the signature exhibited accurate predictions of survival at 1-, 3- and 5- years with the area under the curve (AUC) values of 0.708, 0.689 and 0.854, respectively. In addition, we also observed significant associations between the DRLs signature and various clinical variables, distinct immune landscape and drug sensitivity profiles in GC patients. The low-risk group patients may be more likely to benefit from immunotherapy and chemotherapy. CONCLUSIONS: Our study investigated the role and potential clinical implications of DRLs in GC. The risk model constructed by DRLs demonstrated high accuracy in predicting the survival outcomes of GC and improving the treatment efficacy for GC patients.

Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe.

BACKGROUND: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. METHODS: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. RESULTS: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. CONCLUSIONS: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

AP4M1 as a prognostic biomarker associated with cell proliferation, migration and immune regulation in hepatocellular carcinoma.

BACKGROUND: AP4M1 is a protein-coding gene that plays a crucial role in transporter activity, recognition, and hereditary-associated diseases, but it's largely unknown in cancers. METHODS: The expression level of AP4M1 in cancers was investigated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the correlation between AP4M1 and hepatocellular carcinoma (HCC) clinicopathological parameters were analyzed. Univariate and multifactorial COX regression analyses were performed to clarify the prognostic value of AP4M1 in HCC. The correlation between AP4M1 and immune cell infiltration was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Besides, we verified the biological function of AP4M1 by applying Cell Counting Kit-8 (CCK8), colony formation, and transwell assays. RESULTS: The expression of AP4M1 was significantly elevated in HCC and was correlated with patients' pathological grades, AFP, and BMI. Kaplan-Meier survival curves indicated that patients with AP4M1 overexpression had worse overall survival. Univariate and multivariate COX regression analyses showed that AP4M1 was an independent risk factor affecting the prognosis of HCC. In addition, we observed that AP4M1 positively correlated with most immune checkpoint suppressor genes in HCC. Moreover, in vitro experiments further confirmed that AP4M1 could promote the proliferation and invasion of HCC. CONCLUSIONS: AP4M1 is highly expressed and associated with poor prognosis in HCC. AP4M1 is closely related to cancer-immune regulation and could be a novel target for HCC, and guiding new strategies for the diagnosis and treatment of HCC patients.

SMC1A facilitates gastric cancer cell proliferation, migration, and invasion via promoting SNAIL activated EMT.

BACKGROUND: Structural maintenance of chromosomes protein 1 A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participates in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC). MATERIALS AND METHODS: RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed. Furthermore,the mechanism of SMC1A action was investigated. RESULTS: SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS cells remarkably promoted cell proliferation in vitro and in vivo, migration and invasion, Conversely, knockdown of SMC1A in HGC27 cells inhibited cell proliferation, migration and invasion. Moreover, it's observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAIL. CONCLUSION: Our study revealed that SMC1A promotes EMT process by upregulating SNAIL, which contributes to gastric cancer cell proliferation, migration and invasion. Therefore, targeting SMC1A may be a potential strategy to improve GC therapy.

Integrative Analysis of the Predictive Value of Perilipin Family on Clinical Significance, Prognosis and Immunotherapy of Glioma.

Gliomas are common tumors of the central nervous system. The PLINs family is widely involved in the regulation of lipid metabolism and has been associated with the development and invasive metastasis of various malignancies. However, the biological role of the PLINs family in gliomas is still unclear. TIMER and UALCAN were used to assess PLINs mRNA expression in gliomas. "Survminer" and "Survival" were used to evaluate the connection between PLINs expression and glioma patients' survival. cBioPortal was applied to assess PLINs' genetic alterations in glioblastoma multiforme (GBM) and low-grade glioma (LGG). The correlation of PLINs expression with tumor immune cells was analyzed by TIMER. The expressions of PLIN1, PLIN4, and PLIN5 were decreased in GBM compared to normal tissues. However, PLIN2 and PLIN3 were significantly increased in GBM. Prognostic analysis showed that LGG patients with high PLIN1 expression had better overall survival (OS), and high expression of PLIN2/3/4/5 was associated with unfavorable OS. We further determined that the expression of PLINs members in gliomas was strongly related to tumor immune cells and immune checkpoint-associated genes. PLINS may be potential biomarkers for regulating the tumor microenvironment and predicting the efficacy of immunotherapy. In addition, we determined that PLIN1 may affect glioma patients' therapeutic sensitivity to temozolomide. Our results demonstrated the biological significance and clinical values of PLINs in gliomas and provide a basis for future in-depth exploration of the specific mechanisms of each member of PLINs in gliomas.

Comprehensive analysis of the expression profile and clinical implications of regulator of chromosome condensation 2 in pan-cancers.

The Regulator of Chromosome Condensation 2 (RCC2) is an important gene that regulates mitosis and cytoplasmic division in the cell cycle. Although there have been reported in several individual tumors, an integrative analysis of RCC2 and its clinical significance across diverse cancer types is poorly elucidated. In this study, we performed integrative bioinformatics analyses to profile the expression landscape and assess the prognostic value of RCC2 in pan-cancers. Correlations between RCC2 expression and tumor-infiltrating immune cells, tumor mutation burden (TMB), microsatellite instability (MSI), chemokine and their receptors were analyzed using TCGA, ESTIMATE algorithm, and TISIDB database. We also explored the potential molecular functions of RCC2 through functional enrichment analysis and protein interaction networks. We discovered that RCC2 was highly expressed in various tumor tissues and was closely associated with cancer prognosis. Different RCC2-associated immune infiltration patterns were exhibited in different tumor-infiltrating immune cells. In addition, the RCC2 had a potential role in regulating the tumor immune microenvironment and the formation of cancer-associated fibroblasts (CAFs). Meanwhile, RCC2 showed a significant correlation with TMB, MSI, chemokines and their receptors in different tumor types. The role of RCC2 as a clinical therapeutic target was further revealed from the perspective of the immune microenvironment. In conclusion, RCC2 is closely associated with tumorigenesis and cancer-immune infiltration, and could be a promising prognostic and therapeutic biomarker in diverse cancers.