LCNEC is an aggressive tumor[29].It has unique biological and molecular features. Patients diagnosed with LCNEC have dismal prognosis. Since this tumor is extremely rare, it is very difficult to be clinically diagnosed. It is classified differently due to pathological features[30] [31]. LCNEC has similar features with small cell lung cancer, including aggressiveness, relations with smoking, extremely high rates of progression, certain gene expressions. Standard treatments of LCNEC and are still not well established. Since current treatment results are not satisfactory. There’s emerging need for better clarification of the underlying features of LCNEC and discovery of new options for treatments.
In our study, we used bioinformatics method to reveal key genes and pathways involved in pathogenesis of LCNEC. Results showed that CDC20(Cell Division Cycle 20), KIF11(Kinesin Family Member 11), CDC7(Cell Division Cycle 7), KNTC1 (Kinetochore Associated 1), CCT4(Chaperonin Containing TCP1 Subunit 4), UHRF1(Ubiquitin Like With PHD And Ring Finger Domains 1), RANBP1(Ran-specific binding protein 1), RPS6(Ribosomal protein S6), LMO7(LIM Domain 7), HLA-DMB(HLA class II histocompatibility antigen, DM beta chain) were hub genes involved. Pathways enriched were regulations of mitotic cell cycle, mitotic cell cycle checkpoint, HTLV-1 infection, adaptive immune system. we validated data using sample tissues dissected from LCNEC patients. Further we got three significant important genes: CCT4, CDC20 and KNTC1. They are all protein coding genes. CCT4 (Chaperonin Containing TCP1 Subunit 4) is related to pathways including cooperation of prefoldin and TriC/CCT in actin and tubulin folding ,and cargo trafficking to the periciliary membrane. Gene ontology annotations related to this gene include unfolded protein binding. CDC20 (Cell Division Cycle 20) is related to pathways like CDK-mediated phosphorylation and removal of Cdc6, as well as mitotic roles of polo like kinases. Gene ontology annotations related to this gene include enzyme binding and protein C-terminus binding. KNTC1’s (Kinetochore Associated 1) related pathways are cell cycle, mitotic and mitotic prometaphase.
However, there are limitations to our study. Since LCNEC is an extremely rare disease, the collection of large data set is very difficult. For further studies, we would like to collaborate with other hospitals to gather more data on LCNEC.