Abstract Liver metastasis is one of the most common complications of advanced lung cancer and an important factor influencing patient prognosis and survival. Currently, there are limited effective treatment options for lung cancer patients with liver metastasis, leading to short survival and poor prognosis. In-depth studies of the related molecular mechanisms are crucial for advancing clinical translation and optimizing therapeutic strategies. In recent years, more and more studies of the mechanisms of liver metastasis in lung cancer have performed, particularly in areas such as the roles of different proteins, cell-cell interactions, and changes in the tumor microenvironment. This review summarizes the current understanding of the basic process of lung cancer liver metastasis, regulatory proteins, signaling pathways, tumor microenvironment changes, and clinical treatment progress. Emerging evidence highlights the critical involvement of TGF-β/smad signaling pathway and integrin family proteins in promoting lung cancer liver metastasis. In the tumor microenvironment, various cell types including mononuclear phagocytes, fibroblasts, and hepatocytes contribute to this metastatic process. Clinically, the combination of immunotherapy with chemotherapy, radiotherapy, and antiangiogenic therapy has shown potential to improve treatment outcomes. Furthermore, targeted therapy against specific pathways, proteins, and cells within the tumor microenvironment, as well as the integration of multiple treatment modalities, holds promise for becoming effective strategies in the future clinical management of lung cancer liver metastasis.

Objective : To explore the correlation between the clinical, pathological, genetic features, prognosis, and tumor lymph node metastasis in patients with stage ⅠA-Ⅲ B lung invasive non-mucinous adenocarcinoma(INMA). Methods: A retrospective analysis was conducted on 67 eligible patients with INMA. Clinical data, histopathological assessments, and genetic testing were collected. Disease progression-free survival(PFS) was the primary endpoint through follow-up. The chi-square test or Fisher's exact test was used to analyse the correlation between tumour lymph node metastasis and clinicopathological and genetic characteristics. The Cox proportional hazards regression model and Kaplan-Meier method were used to analyse the impact of tumour lymph node metastasis on prognosis. Results: A total of 67 patients were included, aged 46-77 years, with a median age of 61 years. Age, gender, and smoking history were not significantly associated with tumor lymph node metastasis. Larger tumor diameter, tumor progression, and receiving postoperative adjuvant treatment were associated with tumour lymph node metastasis(P<0.05). Poorer differentiated tumors according to International Association for the Study of Lung Cancer(IASLC) grading system was more likely to have lymph node metastasis(P=0.043). There was no significant difference in the types of driver gene mutations and lymph node metastasis. However,EGFRmutations were more common in patients without lymph node metastasis, while co-mutations were more common in patients with lymph node metastasis. Lymph node metastasis was significantly associated with PFS. Patients without lymph node metastasis had a significantly better PFS compared to those with lymph node metastasis(P=0.002). Under different treatment conditions, patients without lymph node metastasis exhibited a significant advantage in PFS when untreated. While treatment showed a trend toward improved PFS, the difference did not reach statistical significance. Additionally, no significant differences in PFS were observed between patients with or without lymph node metastasis following chemotherapy or targeted therapy. Conclusion Lymph node metastasis in INMA patients is related to tumor size, progression status, and gene co-mutations, and is a key prognostic indicator affecting PFS.

Objective: To investigate the correlations among clinicopathological features, histopathological growth patterns and prognosis of extrapulmonary multiple metastatic(stage ⅣB) pulmonary adenocarcinoma with epidermal growth factor receptor(EGFR) mutations. Methods : A total of 488 eligible patients with adenocarcinoma of stage ⅣB. Clinicopathological data,EGFRgene mutation subtypes, metastatic sites, histopathological growth patterns and survival information were collected. The chi-square test(χ2test) and Fisher's exact probability method were used to detect the correlation between the metastasis status and various clinical characteristics; the Kaplan-Meier method was used to conduct survival analysis on the median Progression-Free Survival(PFS) under different clinical characteristics. Cox univariate and multivariate regression analyses were conducted to evaluate the impact of various clinical characteristics on prognosis. Results : The metastatic patterns of stage ⅣB pulmonary adenocarcinoma withEGFRmutations was correlated with histopathological growth patterns(P<0.05). In the group with multiple metastases in a single organ, the proportion of micropapillary type in the group with multiple metastases in a single organ was higher than that in the group with multiple-organ metastases(51.1%vs41.1%), while the proportion of solid type in the group with multiple-organ metastases was higher than that in the group with multiple metastases in a single organ(23.8%vs14.2%). Multiple brain or multiple bone metastases were correlated with histopathological growth patterns and tumor differentiation degree. Compared with the multiple bone metastases group, the proportion of acinar type decreases in the multiple brain metastasis group, while the proportion of micropapillary type increased. Moreover, the proportion of poorly differentiated tumors increased significantly(P<0.05). Compared with multiple bone metastases, the proportion of poorly differentiated tumors significantly increases in the group with multiple brain metastases. The median progression-free survival(PFS) of patients with a predominant solid growth pattern was shorter than that of patients with other growth patterns(12.7 monthsvs17.8 months,P<0.05). The PFS of patients in the poorly differentiated group was worse than that in the moderately differentiated group(15.6 monthsvs17.8 months,P<0.05). There were significant differences in PFS among patients with common sensitive mutations and rare mutationsEGFR(17.3 monthsvs10.2 months,P<0.01). Cox proportional hazards regression model suggested that solid growth pattern, poor differentiation and rare single gene mutation were adverse prognostic factors. Conclusion In stage ⅣB pulmonary adenocarcinoma patients withEGFRmutations, both the metastatic patterns and metastatic sites are significantly correlated with the histopathological growth patterns of tumors. Moreover, theEGFRmutation subtypes as well as the histopathological growth patterns and differentiation degree of tumors significantly affect the prognosis of patients.

Objective: To explore the high expression level of serum heat shock protein 90α(HSP90α) and gene HSP90 AA1 in cancer tissue, and to discover the prognosis of lung cancer. Methods: A total of 109 cases of lung cancer were collected as the experimental group; 38 lung inflammation groups as the reference group; and 30 healthy controls. The serum HSP90α levels between the three groups were compared; the correlation between HSP90α and clinical parameters were analyzed. The TCGA data were used to analyze the correlation between the expression level of HSP90 AA1 and various pathological features, as well as its influence on the prognosis of lung cancers. Results: The serum HSP90α concentrations in the experimental group were higher than those of the reference group and the control group(P<0.05). The ROC curve area of HSP90α in the diagnosis of lung cancer was 0.898(P<0.05); the expression of HSP90α in the lung squamous cell carcinoma group(LUSC) and the small cell lung cancer group(SCLC) were higher than those in lung adenocarcinoma group(LUAD)(P<0.05); the level of HSP90α decreased when condition alleviated, while increased significantly when disease progressed(P<0.05); Further TCGA database showed that the expression of HSP90 AA1 in cancer tissues was higher than that of adjacent cancer tissues(P<0.05),meanwhile, remarkably increased in LUSC compared with in LUAD(P<0.05). The expression of HSP90 AA1 has no significant correlation with the age, gender, clinical stage, and tumor residue of lung cancer patients. Survival analysis and Cox regression analysis showed that high expression of HSP90 AA1 reduced the overall survival(OS) of lung cancer patients; HSP90 AA1 was an independent prognostic factor for lung cancer patients. Conclusion Serum HSP90α and HSPAA1 in cancer tissues are elevated in patients with lung cancer, which should be used as an auxiliary diagnosis method for lung cancer. Meanwhile they should be used for therapeutic effect observation and survival status prediction.

Purpose To assess the expression of DLL4 in non-small cell lung cancer ( NSCLC) patients and to determine its associa-tion with clinicopathological parameters and prognosis. Methods DLL4 expression was evaluated in NSCLC tissues and adjacent non-cancerous normal lung tissues from 89 patients undergoing surgical treatment by immunohistochemistry. Results DLL4 had high ex-pression in 52 of 89 cases of NSCLC (58. 4%), which was significantly higher than that in adjacent non-cancerous lung tissues (P<0. 05). Moreover, DLL4 overexpression was significantly correlated with TNM stage (P=0. 010 78). Kaplan-Meier survival analysis showed that the overall survival times in patients expressing DLL4 in NSCLC were shorter. Conclusion High level of DLL4 expression is significantly correlated with NSCLC progression and unfavorable prognosis. Thus, DLL4 expression may be used as a clinical param-eter for predictive prognostication of NSCLC patients.