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We present a novel sequencing chemistry implemented as part of the AVITI system. Relying on the proximal DNA binding sites created through DNA amplification on a solid support, avidity sequencing uses multivalent nucleotide ligands on dye-labeled cores to simultaneously form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides by 100x and yield a negligible dissociation rate. We demonstrate the use of avidites within a novel sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing.

Background: Fanconi anemia (FA) group D2 (FANCD2) is a ferroptosis-related gene crucial for DNA damage repair and negatively regulates ferroptosis. Our study aimed to evaluate its prognostic value as well as its association with ferroptosis and immune infiltration in lung adenocarcinoma (LUAD). Methods: Transcriptome sequencing data and clinical information, three independent cohorts, as well as immunohistochemistry, were collected from the TCGA, GEO, and HPA databases, respectively. Univariate and multivariate analyses were used to assess the correlations between FANCD2 expression and overall survival or clinicopathological parameters. cBioPortal was utilized to investigate the FANCD2 alteration status. Gene and protein networks based on FANCD2 interactions were generated using GeneMANIA and STRING, respectively. Based on the CancerSEA database, the function of FANCD2 was explored at the single-cell level. The relationships between FANCD2 expression levels and tumor-infiltrating immune cells and their equivalent gene signatures were analyzed by TIMER, GEPIA, TISIDB, and ssGSEA databases. CIBERSORT was used to analyze the relevance of the infiltration of 24 types of immune cells. Results: The results revealed that FANCD2 expression was significantly upregulated in LUAD and lung squamous cell carcinoma (LUSC) tissues than in normal tissues. Further, the overexpression of FANCD2 was closely associated with poor survival for LUAD patients but not for LUSC patients. FANCD2 expression levels were related to tumor-infiltrating immune cells and their matching gene signatures, including CD8+ T cells, NK cells, DC cells, and Th2 cells in cases of LUAD. Conclusion: FANCD2 was identified as a crucial molecule underlying the synergistic effects of ferroptosis and immunotherapy for LUAD patients.

The gene encoding beta2-adrenergic receptor (β2-AR), adrenoceptor beta 2 (ADRB2), has been reported to closely associated with various cancers. However, its role in lung adenocarcinoma (LUAD) remains controversial. This research shed light on the prognostic value of ADRB2 in LUAD and further explored its association with immune cell infiltration. ADRB2 was significantly decreased in LUAD. ADRB2 expression in LUAD was significantly correlated with gender, smoking status, T classification, lymph node metastasis, and pathologic stage. Patients in the low ADRB2 expression group presented with significantly poorer overall survival (OS) and disease-specific survival (DSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results showed that ADRB2 participates in immune response. The expression of ADRB2 was positively correlated with the infiltration level of most immune cells. Notably, ADRB2 is involved in LUAD progression partly by regulating the immune microenvironment, which may potentially serve as a significant prognostic biomarker as well as a potential drug target.

Background: We aimed to investigate the prognostic value of Four and a half LIM domain protein 1 (FHL1) and its correlation with FHL1 and tumor-infiltration immune cells (TIICs) in lung adenocarcinoma (LUAD). Methods: FHL1 expression status and its influence on clinical characteristics in LUAD and Lung squamous cell carcinoma (LUSC) were collected based on GEPIA, TCGA, GEO, CPTAC, the HPA database, and the GTEx Portal. The ROC curve and Kaplan-Meier plots were used to assess the value of FHL1 expression levels in the diagnosis and prognosis of LUAD and LUSC. The interaction network revealed the related genes and proteins of FHL1 by GeneMANIA and STRING. The functional enrichment analysis based on FHL1 and FHL1-related differentially expression genes (DEGs) was conducted by the “clusterProfile” package and Metascape, respectively. The correlation analysis between FHL1 expression and tumor immunity was performed using TISIH, TIMER, and TISIDB. cBioPortal was used to investigate the mutation status between FHL1 and representative immune checkpoints. Results: The results showed that FHL1 expression was significantly lower in tumors relative to adjacent standard samples, and downregulated FHL1 predicted a worse prognosis for LUAD than that for LUSC. Additionally, FHL1 participated in the interleukin 15 mediated signaling pathway, response to interleukin-9, and neutrophil-mediated cytotoxicity. It was also positively correlated with TIICs (B cells, CD8+T, CD4+T cells, macrophages, neutrophils, and DC), immune checkpoints (CD80, CD48, VTCN, and PVR), and chemokines (CCL5, CCL17, CCL20 and CXCL8). Conclusion: FHL1 is a powerful prognostic biomarker of immune infiltration.

Background: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing’s syndrome (CS). This study aimed to explore molecular basis and treatment strategy in a patient with PPNAD.Methods: Whole-exome sequencing (WES) was used to reveal the mutation of PRKAR1A gene, with immunohistochemistry (IHC) to observe the expression of mutant PRKAR1A. Low-dose Mitotane followed by unilateral adrenalectomy were performed to control hypercortisolism. Results: A case of 45-year-old female present with classical hypercortisolism as excessive weight gain, central obesity, and intractable hypertension. She experienced adrenal adenoma surgery 10 years ago with no improvement. Low dosage of Mitotane was used for 7 months to control the severe hypercortisolism. Then laparoscopic unilateral adrenalectomy was performed and pathological features supporting PPNAD. The germline mutation (c.1A>G) in the start codon of PRKAR1A (Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha) gene was identified. Notably, the body weight and hypertension were improved obviously one year later even if she discontinued with the Mitotane treatment.Conclusion: Low-dose Mitotane followed by unilateral adrenalectomy showed satisfied treatment effect in this patient, which may be an alternative treatment for PPNAD patient instead of bilateral adrenalectomy.