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| ID | Type | Description | Link |
|---|---|---|---|
| IRB-2026-735 | Other Identifier | Ethics Committee of Zhejiang Cancer Hospital |
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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:
The primary outcome measures will include overall survival (OS) and progression-free survival (PFS). Secondary outcome measures will include objective response rate (ORR), disease control rate (DCR), treatment-specific clinical benefit, and the association between genomic alterations, PD-L1 expression, and therapeutic outcomes.
The goal of this observational study is to investigate the clinical and biological significance of LKB1 (STK11) alterations in patients with non-small cell lung cancer (NSCLC) and to determine whether LKB1 mutation status, together with co-occurring genomic alterations, can predict therapeutic response and survival outcomes across different treatment strategies.
The main question this study aims to answer is whether LKB1-driven molecular subgroups can define distinct clinical behaviors, immune phenotypes, and treatment vulnerabilities in NSCLC patients.
Participants included in this study are adult patients diagnosed with NSCLC who have available tumor tissue samples, genomic sequencing data, PD-L1 immunohistochemical evaluation, and clinical follow-up information. Approximately 300 patients with NSCLC will be retrospectively enrolled. Clinical characteristics, including age, sex, smoking history, pathological subtype, TNM stage, treatment history, and survival outcomes, will be collected from medical records.
Tumor tissue samples will be analyzed using targeted next-generation sequencing to identify genomic alterations involving LKB1 (STK11), KRAS, KEAP1, TP53, and other cancer-related genes. Immunohistochemistry will be performed to evaluate LKB1 protein expression and PD-L1 expression levels. Genomic profiles will be integrated with clinical characteristics and treatment information, including chemotherapy, targeted therapy, immune checkpoint inhibitor therapy, and combination treatment regimens.
The study will classify patients according to biologically relevant genomic backgrounds, with LKB1 mutation as the primary molecular factor and KRAS, KEAP1, and TP53 alterations considered as important co-molecular modifiers. Different genomic subgroups will be compared to determine their associations with PD-L1 expression patterns, treatment responses, and long-term clinical outcomes.
The study will evaluate whether LKB1 alteration contributes to therapeutic heterogeneity by influencing immune checkpoint inhibitor efficacy and modifying the prognostic impact of PD-L1 expression. In addition, this study will explore whether specific LKB1-associated genomic subtypes represent distinct patient populations with different responses to immunotherapy, chemotherapy, or targeted treatment approaches.
Participants will not receive any experimental intervention as part of this study. All clinical treatments will have been administered according to routine medical practice. The study will analyze previously collected clinical and molecular data, together with long-term follow-up information, to establish an LKB1-centered genomic classification framework for personalized treatment stratification in NSCLC.
The primary outcomes of this study are overall survival (OS) and progression-free survival (PFS). Secondary outcomes include objective response rate (ORR), disease control rate (DCR), treatment-specific clinical benefit, and the relationship between genomic alterations, PD-L1 expression, and therapeutic outcomes.
This study aims to improve the understanding of how LKB1 loss influences tumor immune biology and treatment response in NSCLC and may provide a clinically applicable strategy for identifying patients who are more likely to benefit from specific therapeutic approaches.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) stratified by STK11/LKB1 mutation and co-mutation profiles | Overall survival (OS), measured in months, is defined as the time from initiation of first-line systemic therapy to death from any cause. Patients who are alive at the last follow-up will be censored at the date of last known survival status. Survival status and date of death will be collected by retrospective review of medical records, follow-up records, and/or death registry data when available. STK11/LKB1 mutation status and co-mutation profiles, including KRAS, KEAP1, and TP53, will be assessed using next-generation sequencing or other clinically validated molecular testing methods. OS will be summarized according to STK11/LKB1 mutation status and co-mutation profiles. |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of co-mutation profiles with TNM stage and treatment prognostic interaction | TNM stage, measured as a categorical clinical stage variable, will be collected from medical records and pathology reports according to the American Joint Committee on Cancer (AJCC) TNM staging system. Stage will be recorded as stage I, II, III, or IV, based on the documented stage at initial diagnosis or before initiation of first-line systemic therapy. STK11/LKB1 mutation status and co-mutation profiles, including KRAS, KEAP1, and TP53, will be assessed using next-generation sequencing or other clinically validated molecular testing methods. TNM stage distribution will be summarized according to STK11/LKB1 mutation status and co-mutation profiles. |
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022 | Hangzhou | Zhejiang | 310022 | China |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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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.
| 1year |
| PD-L1 TPS distribution in STK11/LKB1-mutant and wild-type molecular subgroups | PD-L1 tumor proportion score (TPS), measured as the percentage of viable tumor cells showing partial or complete membranous PD-L1 staining, will be assessed by immunohistochemistry (IHC) using available tumor tissue samples. TPS will be recorded as a continuous percentage from 0% to 100% and may also be categorized according to clinically used cutoffs, such as <1%, 1%-49%, and >=50%, when applicable. STK11/LKB1 mutation status and co-mutation profiles, including KRAS, KEAP1, and TP53, will be assessed using targeted next-generation sequencing or other clinically validated molecular testing methods. PD-L1 TPS will be summarized according to STK11/LKB1 mutation status and co-mutation profiles. | 3months |
| Correlation between STK11/LKB1 mutation status and clinicopathological features of NSCLC | Collect clinical data including tumor stage, pathological subtype, differentiation, smoking status, age, gender, ECOG status. Analyze the distribution of STK11/LKB1-mutant and wild-type patients in different clinicopathological subgroups. | 3months |
| 3months |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |