TBX5基因在肺癌中的研究进展

T-box转录因子(T-box transcription factor gene,TBX)基因涉及器官的发生,TBX5在人的正常心脏和肺组织中表达水平最高。TBX5的缺乏可能导致胸廓发育畸形和膈肌发育异常,其异位表达和过表达会诱导细胞凋亡和抑制细胞生长。既往研究发现了TBX5在食管腺癌、胃癌、结肠癌和乳腺癌的发生和发展中的潜在作用。我们对TBX2亚家族的基因表达和预后之间的关系进行了综述,同时探究TBX5在调控肺癌发生发展机制中的研究进展。虽然TBX5和肺癌发生之间的关系尚不明确,不过TBX5可以显著抑制人体内肿瘤生长,其表达水平和肺癌的进展呈现负相关。由此,TBX5的基因表达水平和甲基化程度是潜在的表证肺癌增殖和转移的生物标志物,具有作为肺癌治疗靶点的潜力。

The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy

Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogramming.However,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched.Herein,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)databases.All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes.Each subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical outcome.We further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents.Collectively,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors(ICIs)by conducting systematic literature search in electronic databases up to May 31,2021.The main outcomes including overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and durable clinical benefit(DCB)were correlated with tumor genomic features.A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies.The Kirsten rat sarcoma viral oncogene homolog G12C(KRAS^(G12C))mutation combined with tumor protein P53(TP53)mutation revealed the promising efficacy of ICI therapy in these patients.Furthermore,patients with epidermal growth factor receptor(EGFR)classical activating mutations(including EGFRL858Rand EGFRΔ19)exhibited worse outcomes to ICIs in OS(adjusted hazard ratio(HR),1.40;95%confidence interval(CI),1.01-1.95;P=0.0411)and PFS(adjusted HR,1.98;95%CI,1.49-2.63;P<0.0001),while classical activating mutations with EGFR^(T790)Mshowed no difference compared to classical activating mutations without EGFR^(T790)Min OS(adjusted HR,0.96;95%CI,0.48-1.94;P=0.9157)or PFS(adjusted HR,0.72;95%CI,0.39-1.35;P=0.3050).Of note,for patients harboring the Usher syndrome type-2A(USH2A)missense mutation,correspondingly better outcomes were observed in OS(adjusted HR,0.52;95%CI,0.32-0.82;P=0.0077),PFS(adjusted HR,0.51;95%CI,0.38-0.69;P<0.0001),DCB(adjusted odds ratio(OR),4.74;95%CI,2.75-8.17;P<0.0001),and ORR(adjusted OR,3.45;95%CI,1.88-6.33;P<0.0001).Our findings indicated that,USH2A missense mutations and the KRAS^(G12C)mutation combined with TP53 mutation were associated with better efficacy and survival outcomes,but EGFR classical mutations irrespective of combination with EGFR^(T790)Mshowed the opposite role in the ICI therapy among lung cancer patients.Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.