LKB1 Expression and Clinical Outcomes in Non-Small Cell Lung Cancer: A Retrospective Cohort Study

NCT07710599 | Active Not Recruiting

• 2 other identifiers: IRB-2026-735(IIT)IRB-2026-735
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to investigate whether LKB1 alterations can serve as a clinically meaningful biomarker for predicting therapeutic response and survival outcomes in patients with non-small cell lung cancer (NSCLC), and to determine how LKB1 mutation status together with co-occurring genomic alterations influences treatment sensitivity across different therapeutic strategies. This study will include adult patients diagnosed with NSCLC who underwent surgical resection or tumor biopsy, genomic profiling, PD-L1 immunohistochemical evaluation, and clinical follow-up. Tumor samples from approximately 300 patients will be analyzed for genomic alterations involving LKB1 (STK11), KRAS, KEAP1, TP53, and other cancer-related genes. Clinical characteristics, including age, sex, smoking history, TNM stage, treatment modalities (chemotherapy, targeted therapy, immunotherapy), and survival outcomes will be collected and integrated for comprehensive analysis. The main questions this study aims to answer are:

1. 1.Does LKB1 mutation status independently predict clinical outcomes, including overall survival and progression-free survival, in patients with NSCLC?
2. 2.Does LKB1 alteration modify the predictive value of PD-L1 expression and determine differential responses to immunotherapy, chemotherapy, and targeted therapy?
3. 3.Do distinct genomic backgrounds defined by LKB1, KRAS, KEAP1, and TP53 co-mutation patterns represent biologically and clinically meaningful subgroups with different therapeutic vulnerabilities?
4. 4.Can an LKB1-centered genomic classification model improve patient stratification and provide a more accurate framework for personalized treatment selection in NSCLC?

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) of first-line systemic therapy stratified by STK11/LKB1 mutation status

  Progression-free survival (PFS), measured in months, is defined as the time from initiation of first-line systemic therapy to the first documented disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by retrospective review of radiologic imaging reports and medical records, using RECIST v1.1 criteria when available or treating physician-documented progression in routine clinical practice. LKB1 expression status will be assessed by immunohistochemistry (IHC) using archived tumor tissue and categorized as LKB1-low/loss versus LKB1-preserved/high expression according to the study-defined cutoff. PFS will be summarized according to LKB1 expression status and first-line treatment category.

  1 year

Secondary Outcomes (3)

• Overall Survival (OS) stratified by STK11/LKB1 mutation and co-mutation profiles

  1year

• PD-L1 TPS distribution in STK11/LKB1-mutant and wild-type molecular subgroups

  3months

• Correlation between STK11/LKB1 mutation status and clinicopathological features of NSCLC

  3months

Other Outcomes (1)

• Correlation of co-mutation profiles with TNM stage and treatment prognostic interaction

  3months

Study Arms (1)

All Non-Small Cell Lung Cancer Patients

Retrospectively enrolled 300 patients diagnosed with non-small cell lung cancer, archived frozen tumor tissues were collected to detect LKB1 protein expression via immunohistochemistry. Subgroup analysis of LKB1 positive/negative status will be performed statistically after data collection, no prospective intervention or treatment manipulation for subjects.

Eligibility Criteria

• Age: 45 Years - 94 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This retrospective study enrolls 300 patients with pathologically confirmed non-small cell lung cancer with archived frozen tumor samples. All eligible participants received routine clinical pathological examination, targeted gene panel sequencing covering STK11, KRAS, KEAP1, TP53and PD-L1 IHC testing. We collect real-world clinical data, treatment regimens and long-term follow-up data to analyze the predictive value of STK11 mutation combined with co-mutation profiles on chemotherapy, targeted therapy and immune checkpoint inhibitor efficacy.

You may qualify if:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Patients who received first-line systemic therapy, including chemotherapy, targeted therapy, immune checkpoint inhibitor therapy, or combined treatment.
• Available clinicopathologic data, including TNM stage, treatment information, and follow-up records.
• Available tumor tissue samples or clinically validated molecular testing results for assessment of STK11/LKB1 status and co-mutation profiles, including KRAS, KEAP1, and TP53.
• Available PD-L1 immunohistochemistry (IHC) results or sufficient tumor tissue for PD-L1 TPS assessment, when applicable.

You may not qualify if:

• Pathological diagnosis of small cell lung cancer or mixed small cell/non-small cell lung cancer tumors.
• Insufficient tumor tissue or unavailable testing results that prevent assessment of STK11/LKB1 status, co-mutation profiles, or PD-L1 expression.
• Missing key clinical information, treatment records, or follow-up data required for survival analysis.
• Patients who did not receive first-line systemic therapy.

Sponsors & Collaborators

• Ling Zhiqiang: lead

Study Sites (1)

Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022

Hangzhou, Zhejiang, 310022, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

The 300 cases of non-small cell lung cancer frozen tissue specimens are stored long-term in a -80°C refrigerator of the pathology biobank. The retained tissue samples contain intact genomic DNA, which can be used for DNA extraction if needed in subsequent related research. All specimen use strictly follows the approved ethical protocols.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof., M.D., PhD,

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 17, 2026
• Study Start: January 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 17, 2026

Record last verified: 2026-07

Locations

CN (1)