Clinical Value of Human Endogenous Retrovirus-H Long Terminal Repeat Associating 2 (HHLA2) in Small Cell Lung Cancer.

Objective: Human endogenous retrovirus-H long terminal repeat associating 2 (HHLA2) is a new immune checkpoint in the B7 family, and the value of HHLA2 in small cell lung cancer (SCLC) is unknown. Methods: We retrospectively detected HHLA2 expression by immunohistochemistry in SCLC patients. Moreover, plasma biomarkers of SCLC were detected retrospectively. Results: Seventy-four percent of SCLC patients exhibited HHLA2 expression. HHLA2 staining was localised within the nucleus of SCLC cells, while no staining was detected in normal lung tissue specimens. The correlation between HHLA2 expression and clinical factors was also analysed. Limited stage (LS) SCLC was more common than extensive stage (ES) SCLC among patients with HHLA2 staining. SCLC patients without metastasis had higher HHLA2 expression than SCLC patients with metastasis. HHLA2 expression was more frequently detected in the group with a tumour size greater than 5 cm than in the group with a tumour size less than 5 cm. The proportion of patients with HHLA2-positive staining was greater in the stage III and IV SCLC groups than in the stage I and II SCLC groups. A high proportion of SCLC patients with HHLA2-positive staining had a survival time <2 years. Neuron-specific enolase (NSE), CEA and Ki-67 levels were measured. The NSE level in the HHLA2-positive group was significantly greater than that in the HHLA2-negative group. The CEA and Ki-67 levels did not significantly differ between the HHLA2-positive and HHLA2-negative patients, nor were age, sex, smoking status, nodal metastasis status, Karnofsky Performance Scale (KPS) score, or Ki-67 expression score. HHLA2-positive SCLC patients had higher tumour stages and shorter 2-year survival times than HHLA2-negative patients did. Conclusion: The new immune molecule HHLA2 may be an ideal clinical biomarker for predicting SCLC progression and could serve as a new immunotherapy target in SCLC.

Berberine inhibits non-small cell lung cancer cell growth through repressing DNA repair and replication rather than through apoptosis.

At present, there are still many problems in the treatment of lung cancer, such as high cost, side effects and low quality of life. The advantages of traditional Chinese medicine (TCM) in the treatment of lung cancer are reflected. Berberine has been increasingly popular in colorectal cancer treatment, but little is known about its bioactivity against non-small cell lung cancer (NSCLC). Cell proliferation, cell apoptosis, cDNA microarray, gene and protein expression, and NSCLC transplanted tumour growth were performed. Berberine suppressed NSCLC cell proliferation and colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously transplanted tumour lung tumour models, leading to prolonged survival of tumour-bearing mice. However, berberine did not induce the cleavage of Caspase 3 and PARP1, and could not induce apoptosis in all NSCLC cells. Moreover, 646 genes were differentially expressed upon berberine administration, which were involved in seven signal pathways, such as DNA replication. In cDNA microarray, berberine downregulated the expression of RRM1, RRM2, LIG1, POLE2 that involving DNA repair and replication. Our findings demonstrate that berberine inhibits NSCLC cells growth through repressing DNA repair and replication rather than through apoptosis. Berberine could be used as a promising therapeutic candidate for NSCLC patients.

Transcriptome and single-cell analysis reveal the contribution of immunosuppressive microenvironment for promoting glioblastoma progression.

Background and objectives: GBM patients frequently exhibit severe local and systemic immunosuppression, limiting the possible efficacy of immunotherapy strategies. The mechanism through which immunosuppression is established in GBM tumors is the key to successful personalized immunotherapies. Methods: We divided GBM patients into subtypes according to the expression characteristics of the TME typing-related signature matrix. WGCNA analysis was used to get co-expressed gene modules. The expression activity of hub genes retrieved from co-expressed modules was validated in two single-cell datasets. Then, cell-cell interaction was calculated. Results: Four subtypes were identified in the TCGA and CGGA RNA-seq datasets simultaneously, one of which was an immunosuppressive subtype rich in immunosuppressive factors with low lymphocyte infiltration and an IDH1 mutation. Three co-expressed gene modules related to the immunosuppressive subtype were identified. These three modules are associated with the inflammatory response, angiogenesis, hypoxia, and carbon metabolism, respectively. The genes of the inflammatory response were mainly related to myeloid cells, especially TAM, angiogenesis was related to blood vessels; hypoxia and glucose metabolism were related to tumors, TAM, and blood vessels. Moreover, there was enhanced interaction between tumor cells and TAM. Discussion: This research successfully found the immunosuppressive subtype and the major cell types, signal pathways, and molecules involved in the formation of the immunosuppressive subtype and will provide new clues for the improvement of GBM personalized immunotherapy in the future.