The purpose of this study is to understand the correlation of symptom distresses and coping strategies of patients with lung cancer. Seventy-three patients with non-small cell lung cancer from the cancer center or ward in the two medical centers located in northern Taiwan participated. The instruments used in this study were the Symptom Distress Scale and Coping Strategies Scale. The results of the study showed that the degree of symptom distress during the therapeutic period was mild to moderate. When patients were confronted with symptom distress, they combined problem- and emotion-focused coping strategies. Participants with higher physical symptom distress had higher psychological distress and emotion-focused coping strategy frequency. It was also found that the distress of tension-anxiety and age explained 39.4% of variance in physical symptom distresses. The physical symptom distresses and the frequency of emotion-focused coping strategy frequency explained 48.8% of variance in the psychologic symptom distresses. Finally, it is recommend that a support group be established to enable sharing of experiences and emotional support among patients.

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

Rationale: Lung adenocarcinoma (LUAD) is an aggressive disease with high propensity of metastasis. Among patients with early-stage disease, more than 30% of them may relapse or develop metastasis. There is an unmet medical need to stratify patients with early-stage LUAD according to their risk of relapse/metastasis to guide preventive or therapeutic approaches. In this study, we identified 4 genes that can serve both therapeutic and diagnostic (theranostic) purposes. Methods: Three independent datasets (GEO, TCGA, and KMPlotter) were used to evaluate gene expression profile of patients with LUAD by unbiased screening approach. Upon significant genes uncovered, functional enrichment analysis was carried out. The predictive power of their expression on patient prognosis were evaluated. Once confirmed their theranostic roles by integrated bioinformatics, we further conducted in vitro and in vivo validation. Results: We found that four genes ( ADAM9 , MTHFD2 , RRM2, and SLC2A1) were associated with poor patient outcomes with an increased hazard ratio in LUAD. Knockdown of them, both separately and simultaneously, suppressed lung cancer cell proliferation and migration ability in vitro and prolonged survival time in metastatic tumor mouse models. Moreover, these four biomarkers were found to be overexpressed in tumor tissues from LUAD patients, and the total immunohistochemical staining scores correlated with poor prognosis. Conclusions: These results suggest that these four identified genes could be theranostic biomarkers for stratifying high-risk patients who develop relapse/metastasis in early-stage LUAD. Developing therapeutic approaches for the four biomarkers may benefit early-stage LUAD patients after surgery.

No abstract

Rationale: Brain metastasis in patients with lung cancer is life-threatening. However, the molecular mechanism for this catastrophic disease remains elusive, and few druggable targets are available. Therefore, this study aimed to identify and characterize proteins that could be used as therapeutic targets. Methods: Proteomic analyses were conducted to identify differentially expressed membrane proteins between brain metastatic lung cancer cells and primary lung cancer cells. A neuronal growth-associated protein, brain acid soluble protein 1 (BASP1), was chosen for further investigation. The clinical relevance of BASP1 in lung adenocarcinoma was first assessed. Tyrosine kinase activity assays and in vitro and in vivo functional assays were conducted to explore the oncogenic mechanisms of BASP1. Results: The protein levels of BASP1 were positively associated with tumor progression and poor prognosis in patients with lung adenocarcinoma. Membrane-bound BASP1 increased EGFR signaling and stabilized EGFR proteins by facilitating their escape from the ubiquitin-proteasome pathway. Reciprocally, activation of EGFR recruited more BASP1 to the plasma membrane, generating a positive feedback loop between BASP1 and EGFR. Moreover, the synergistic therapeutic effects of EGFR tyrosine kinase inhibitor and arsenic trioxide led to a reduction in the level of BASP1 protein observed in lung cancer cells with acquired resistance to EGFR inhibitors. Conclusions: The reciprocal interaction between BASP1 and EGFR facilitates EGFR signaling in brain metastatic lung cancer. Targeting the newly identified BASP1-EGFR interaction could open new venues for lung cancer treatment.