Co-existing squamous cell carcinoma and chronic myelomonocytic leukemia with ASXL1 and EZH2 gene mutations: A case report.

BACKGROUND: Chronic myelomonocytic leukemia (CMML), a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms, has a generally poor prognosis, and easily progresses to acute myeloid leukemia. The simultaneous incidence of hematologic malignancies and solid tumors is extremely low, and CMML coinciding with lung malignancies is even rarer. Here, we report a case of CMML, with ASXL1 and EZH2 gene mutations, combined with non-small cell lung cancer (lung squamous cell carcinoma). CASE SUMMARY: A 63-year-old male, suffering from toothache accompanied by coughing, sputum, and bloody sputum for three months, was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital. Based on morphological results, the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung. After receiving azacitidine, programmed cell death protein 1, and platinum-based chemotherapy drugs, the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea. CONCLUSION: During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.

Prognostic biomarkers correlated with immune infiltration in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related mortality in men and women globally. Non-small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85-90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and metastasis rates of NSCLC are as high as 30-40% with the 5-year overall survival rate being less than 15%. Therefore, it is necessary to explore the pathogenesis of NSCLC at the genetic level and identify prognostic biomarkers and novel therapeutic targets. Here, we aimed to identify mutated genes with high frequencies in Chinese NSCLC patients using next-generation sequencing and to investigate their relationships with the tumor mutation burden (TMB) and tumor immune microenvironment. A total of 110 NSCLC patients were enrolled to profile the genetic variations. Mutations in EGFR (62.37%), TP53 (61.29%), LRP1B (13.98%), FAT1 (12.90%), KMT2D (11.83%), CREBBP (10.75%), and RB1 (9.68%) were most prevalent. TP53, LRP1B, KMT2D, and CREBBP mutations were all significantly associated with high TMB (P < 0.05 or P < 0.01). The infiltrating levels of immune cells and immune molecules were enriched significantly in the LRP1B mutation group. LRP1B mutations significantly correlated with stimulating and inhibitory immunoregulators. Gene set enrichment analysis revealed that cell cycle, the Notch signaling pathway, the insulin signaling pathway, and the mTOR signaling pathway are related to LRP1B mutations in the immune system. LRP1B mutations may be of clinical importance in enhancing the anti-tumor immune response and may be a promising biomarker for predicting immunotherapy responsiveness.

Construction of a protein-protein interaction network for chronic myelocytic leukemia and pathway prediction of molecular complexes.

BACKGROUND: Chronic myelocytic leukemia is a disease that threatens both adults and children. Great progress has been achieved in treatment but protein-protein interaction networks underlining chronic myelocytic leukemia are less known. OBJECTIVE: To develop a protein-protein interaction network for chronic myelocytic leukemia based on gene expression and to predict biological pathways underlying molecular complexes in the network. MATERIALS AND METHODS: Genes involved in chronic myelocytic leukemia were selected from OMIM database. Literature mining was performed by Agilent Literature Search plugin and a protein-protein interaction network of chronic myelocytic leukemia was established by Cytoscape. The molecular complexes in the network were detected by Clusterviz plugin and pathway enrichment of molecular complexes were performed by DAVID online. RESULTS AND DISCUSSION: There are seventy-nine chronic myelocytic leukemia genes in the Mendelian Inheritance In Man Database. The protein-protein interaction network of chronic myelocytic leukemia contained 638 nodes, 1830 edges and perhaps 5 molecular complexes. Among them, complex 1 is involved in pathways that are related to cytokine secretion, cytokine-receptor binding, cytokine receptor signaling, while complex 3 is related to biological behavior of tumors which can provide the bioinformatic foundation for further understanding the mechanisms of chronic myelocytic leukemia.