DescriptionAlternative splicing has been suggested to play important roles in cell cycle regulation and cancer, however the underlying echanisms are still lacking. This project examined the effects of PUF60 on the alternative splicing regulatory network in two human lung cancer cell lines: PC9 and A549. Both gene expression and alternative splicing pofiles were generated based on RNA-sequencing datasets from PUF60 knockdown lung cancer cell lines and the corresponding control samples. Our study found that PUF60 regulated the alternative splicing of the genes in lung cancer.
OEP004324
Description
OEP004321
DescriptionA novel personalized tumor-informed technology named PROPHET using deep sequencing of 50 patient-specific variants developed to detect molecular residual disease (MRD) with a limit of detection of 0.004%. We applied PROPHET and state-of-the-art fixed-panel assays to 760 plasma samples from 181 prospectively enrolled early-stage non-small cell lung cancer (NSCLC) patients. PROPHET showed higher sensitivity of 45% at baseline with ctDNA fraction as low as 0.001%. PROPHET outperformed fixed-panel assays in prognostic analysis and demonstrated 299 days lead-time to radiological recurrence. Personalized non-canonical variants accounted for 98.2% and had a prognostic effect similar to canonical variants. The proposed TNMB classification outperformed TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET showed the potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings have profound clinical value and highlight the potential advantages of personalized cancer techniques in MRD detection.
OEP004204
DescriptionKRAS mutations are causally linked to pro-tumor inflammation and identified as driving factors in tumorigenesis. Here, using multi-omics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS mutant iCCA. In KRAS mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant anti-tumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti-PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in KRAS mutant iCCA patients were significantly associated with superior response to anti-PD-1 immunotherapy.
OEP003755
DescriptionIntrahepatic cholangiocarcinoma (iCCA) exhibits extensive intratumoral heterogeneity and extremely high mortality rate. Here, we performed WES, RNA-seq, TCR-seq and multiplexed immunofluorescence on 207 tumor regions from 45 iCCA patients. Over half of iCCA displayed intratumoral heterogeneity of immune infiltration, and iCCA were classified into sparsely, heterogeneously, and highly infiltrated, with distinct immunogenomic characteristics. Sparsely infiltrated tumors showed T cells sequestered at tumor margins and active copy number loss of clonal neoantigens. Heterogeneously infiltrated tumors exhibited different distributions of immune cells and also distinct tumor evolution among regions. Highly infiltrated tumors were characterized by extensive activation of both lymphocytes and myeloid cells, and similar TCR repertoire across tumor regions, but counteracted with T cell exhaustion and pervasive antigen presentation defects. Our work sculpted the dynamic tumor-immune interactions and developed a robust classification system to divide iCCA patients into high and low immune evasion groups with different prognosis.
OEP002560
Description
OEP002770
DescriptionEarly detection of PDAC using cfDNA methylome
OEP003868
DescriptionTranscriptomic profiles of Sphingobium xenophagum strains under different culture conditions were analyzed comparatively.
OEP002610
DescriptionMetagenomic raw data of the bottom water layers and surface sediments of the Changjiang River Estuary and the Eastern China Sea.
OEP001524
DescriptionSingle-cell transcriptomics of human bronchoalveolar lavage fluid from immunosuppression in late sepsis patients and healthy controls
OEP003526