Unraveling Immune Heterogeneity across Pan-Cancer and Deep Insights in Lung Adenocarcinoma based on Alternative Splicing.

Alternative splicing (AS) participates in tumor development and tumor microenvironment formation. However, the landscape of immune infiltrating AS events (IIASE) in pan-cancer and mechanisms of AS in lung adenocarcinoma (LUAD) have not been comprehensively characterized. We systematically profiled the IIASE landscape of pan-cancer using data from The Cancer Genome Atlas (TCGA), analyzing both commonalities and specific characteristics among different cancer types.

Up-regulated SPP1 increases the risk from IPF to lung cancer via activating the pro-tumor macrophages.

The incidence of lung cancer (LC) in Idiopathic Pulmonary Fibrosis (IPF) patients is more than twice that in non-IPF. This study aims to investigate IPF-to-LC pathogenesis and to develop a predictor for detecting IPF predisposing patients to LC. We conducted unsupervised clustering to detect high-risk subtypes from IPF to LC.

Mutant RB1 enhances therapeutic efficacy of PARPis in lung adenocarcinoma by triggering the cGAS/STING pathway.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved for cancer therapy according to their synthetic lethal interactions, and clinical trials have been applied in non-small cell lung cancer. However, the therapeutic efficacy of PARPis in lung adenocarcinoma (LUAD) is still unknown. We explored the effect of a mutated retinoblastoma gene (RB1) on PARPi sensitivity in LUAD.

Synthetic viability induces resistance to immune checkpoint inhibitors in cancer cells.

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment for multiple cancers. However, most of patients encounter resistance. Synthetic viability (SV) between genes could induce resistance.

A genetic map of the chromatin regulators to drug response in cancer cells.

Background: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging.

Methods: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets.

Results: Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected.

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade.

Background: Mutations in BRCA1 or BRCA2 (BRCA1/2) cause homologous recombination deficiency (HRD). Ovarian cancer (OvCa) patients harbouring HRD beyond BRCA1/2 mutation result in a state referred to as "BRCAness". OvCa with BRCAness could benefit from PARP inhibitors.

Pan-cancer multi-omics analyses reveal crosstalk between the Hippo and immune signaling pathways in the tumor microenvironment.

The Hippo signaling pathway is critical for carcinogenesis. However, the roles of the Hippo signaling pathway in the tumor immune microenvironment have been rarely investigated. This study systematically analyzed the relationship between the Hippo signaling pathway and immune cell infiltration across 32 cancer types.

A transcriptional signature detects homologous recombination deficiency in pancreatic cancer at the individual level.

Pancreatic cancer (PC) with homologous recombination deficiency (HRD) has been reported to benefit from poly ADP-ribose polymerase (PARP) inhibitors. However, accurate identification of HRD status for PC patients from the transcriptional level is still a great challenge. Here, based on a relative expression ordering (REO)-based algorithm, we developed an HRD signature including 24 gene pairs (24-GPS) using PC transcriptional profiles from The Cancer Genome Atlas (TCGA).

Discovering a qualitative transcriptional signature of homologous recombination defectiveness for prostate cancer.

The discovery of homologous recombination deficiency (HRD) biomarkers in prostate cancer is important for patients who will benefit from poly ADP-ribose polymerase inhibitor (PARPi). Here, we developed a transcriptional homologous recombination defectiveness (HRDness) signature, comprising 16 gene pairs (16-GPS), for prostate cancer by a relative expression ordering (REO)-based discovery procedure. Subsequently, two newly subtypes classified by 16-GPS showed a higher significance level in various clinicopathological and HRD features than subtypes obtained by other methods, such as HRDetect.

Revealing biomarkers associated with PARP inhibitors based on genetic interactions in cancer genome.

Poly (ADPribose) polymerase inhibitors (PARPis) are clinically approved drugs designed according to the concept of synthetic lethality (SL) interaction. It is crucial to expand the scale of patients who can benefit from PARPis, and overcome drug resistance associated with it. Genetic interactions (GIs) include SL and synthetic viability (SV) that participate in drug response in cancer cells.