The goal of this observational study is to investigate the predictive value of exosome characteristics in patients with advanced non-small cell lung cancer (NSCLC) and malignant pleural effusion (MPE). The main question it aims to answer is:

Can the long RNA profile of exosomes derived from plasma and malignant pleural effusion predict treatment response in patients with advanced NSCLC and MPE? Participants who are scheduled to receive standard systemic therapy (including immunotherapy, chemotherapy, or targeted therapy) as part of their regular medical care will be enrolled. Researchers will collect paired samples of peripheral blood and malignant pleural effusion at baseline and key time points during treatment to analyze the exosomal long RNA profiles and correlate them with treatment efficacy and survival outcomes.

Inclusion Criteria:

- Confirmed advanced-NSCLC Aged 18-75 years. ECOG performance status of 0-1. At least one measurable lesion as per RECIST 1.1. Adequate bone marrow, liver, and renal function. Willing and able to provide written informed consent.

Exclusion Criteria:

- Mixed small cell lung cancer histology. Symptomatic or untreated brain metastases. Uncontrolled cardiovascular diseases or severe comorbidities. Active hepatitis B/C or HIV infection.

The study will enroll approximately 100-120 patients with histologically or cytologically confirmed stage IV NSCLC who present with MPE and are scheduled to receive standard systemic therapy (including but not limited to immunotherapy, chemotherapy, or targeted therapy).