establishing-competing-risk-regression-nomogram-model-for-survival

Establishing a Competing Risk Regression Nomogram Model for Survival Data

The Kaplan&#8211;Meier method and Cox proportional hazards regression model are the most common analyses in the survival framework. These are relatively ...

an-r-based-landscape-validation-of-a-competing-risk-model

An R-Based Landscape Validation of a Competing Risk Model

The Cox proportional hazard model is widely applied for survival analyses in clinical settings, but it is not able to cope with multiple survival ...

Zhejiang University School of Medicine

Methionine is one of the essential amino acids. How tumor cells adapt and adjust their signal transduction networks to avoid apoptosis in a methionine-restricted environment is worthy of further exploration. In this study, we investigated the molecular mechanism of glioma response to methionine restriction, providing a theoretical basis for new treatment strategies for glioma.

SYVN1-MTR4-MAT2A Signaling Axis Regulates Methionine Metabolism in Glioma Cells.

 The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC).  Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Finally, we established a risk score model to describe the characteristics of the model and verify its prediction accuracy. The receiver operating characteristic (ROC) curves of 1, 3, and 5 years of overall survival (OS) were depicted with risk score and some clinical features. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in HCC. The nomogram was drawn by screening indicators with high prognostic accuracy. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. After enrichment of related genes, active behaviors and pathways in high-risk groups were identified and lncRNAs related to poor prognosis were validated . Finally, the impact of MIR4435-2HG upon ICB treatment was uncovered.  After screening through multiple steps, four glycolysis-related lncRNAs were obtained. The risk score constructed with the four lncRNAs was found to significantly correlate with prognosis of samples. From the ROC curve of samples with 1, 3, and 5 years of OS, two indicators were identified with high prognostic accuracy and were used to draw a nomogram. Besides, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4,etc.). Gene enrichment analysis indicated that multiple biological behaviors and pathways were active in the high-risk group.  validation results showed that MIR4435-2HG was highly expressed in the two cell lines, which had a significant impact on the OS of samples. Finally, we corroborated that MIR4435-2HG had intimate relationship with ICB therapy in hepatocellular carcinoma.  We elucidated the crucial role of risk signature in immune cell infiltration and immunotherapy, which might contribute to clinical strategies and clinical outcome prediction of HCC.

Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma.

Metabolic reprogramming is a vital factor in the development of many types of cancer, including colon cancer. Serine metabolic reprogramming is a major feature of tumor metabolism. Yes-associated protein (YAP) participates in organ size control and tumorigenesis. However, the relationship between YAP and serine metabolism in colon cancer is unclear. In this study, RNA sequencing and metabolomics analyses indicated significant enrichment of the glycine, serine, and threonine metabolism pathways in serine starvation-resistant cells. Short-term serine deficiency inhibited YAP activation, whereas a prolonged response dephosphorylated YAP and promoted its activity. Mechanistically, USP7 increases YAP stability under increased serine conditions by regulating deubiquitination. Verteporfin (VP) effectively inhibited the proliferation of colon cancer cells and organoids and could even modulate serine metabolism by inhibiting USP7 expression. Clinically, YAP was significantly activated in colon tumor tissues and positively correlated with the expression of phosphoglycerate dehydrogenase (PHGDH) and USP7. Generally, our study uncovered the mechanism by which serine metabolism regulates YAP via USP7 and identified the crucial role of YAP in the regulation of cell proliferation and tumor growth; thus, VP may be a new treatment for colon cancer.

Serine Metabolism Regulates YAP Activity Through USP7 in Colon Cancer.

Several difficulty scoring systems (DSSs) have been proposed for evaluating difficulty of laparoscopic liver resection (LLR) and no study has validated their performance in a hepatocellular carcinoma (HCC)-only cohort at the same time.

External validation of different difficulty scoring systems of laparoscopic liver resection for hepatocellular carcinoma.

More than half of early breast cancer recurrences occur after 5 years from the initial diagnosis. An individualized estimate of the risk of late-period breast cancer-specific death (LP-BCSD) after 5 years of endocrine therapy (ET) can improve decision-making for extended endocrine therapy (EET).

Competing Nomogram for Late-Period Breast Cancer-Specific Death in Patients with Early-Stage Hormone Receptor-Positive Breast Cancer.

The single progesterone receptor (PR)-positive phenotype (estrogen receptor (ER)-/PR + , sPR positive) is an infrequent and independent biological entity. However, the prognosis of patients with sPR-positive and her-2-negative phenotype is still controversial, and it is not always easy to decide treatment strategies for them.

Estrogen receptor-negative/progesterone receptor-positive and her-2-negative breast cancer might no longer be classified as hormone receptor-positive breast cancer.

Tumor drug resistance is a vital obstacle to chemotherapy in lung cancer. Methionine adenosyltransferase 2A has been considered as a potential target for lung cancer treatment because targeting it can disrupt the tumorigenicity of lung tumor-initiating cells. In this study, we primarily observed the role of methionine metabolism in cisplatin-resistant lung cancer cells and the functional mechanism of MAT2A related to cisplatin resistance.

ArticleTotal : 2	Year
Publication title Cited by 4	2020
Publication title Cited by 2	2022

Article	Year
SYVN1-MTR4-MAT2A Signaling Axis Regulates Methionine Metabolism in Glioma Cells. Frontiers in cell and developmental biology\| PubMed ID: 33859984	2021
Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma. Frontiers in molecular biosciences\| PubMed ID: 33968985	2021
Serine Metabolism Regulates YAP Activity Through USP7 in Colon Cancer. Frontiers in cell and developmental biology\| PubMed ID: 34055773	2021
External validation of different difficulty scoring systems of laparoscopic liver resection for hepatocellular carcinoma. Surgical endoscopy\| PubMed ID: 34406470	2022
Competing Nomogram for Late-Period Breast Cancer-Specific Death in Patients with Early-Stage Hormone Receptor-Positive Breast Cancer. Clinical breast cancer\| PubMed ID: 34627728	2022
Estrogen receptor-negative/progesterone receptor-positive and her-2-negative breast cancer might no longer be classified as hormone receptor-positive breast cancer. International journal of clinical oncology\| PubMed ID: 35397755	2022
Inhibition of MAT2A-Related Methionine Metabolism Enhances The Efficacy of Cisplatin on Cisplatin-Resistant Cells in Lung Cancer. Cell journal\| PubMed ID: 35674024	2022

Haiping Lin

Biography

JoVE Journal Publications

Other Publications