Multi Omics Molecular Characteristics and Immunophenotyping of Lung Signet Ring Cell Carcinoma

Overview

This study aims to reveal the molecular characteristics and immune microenvironmental profile of signet ring cell carcinoma of the lung (LSRCC) in the Chinese population through integrated multi-omics analyses. The project plans to enroll formalin-fixed paraffin-embedded (FFPE) tissue samples and paired adjacent tissues from 39 patients with previously untreated LSRCC to establish a Chinese LSRCC molecular database. Whole-exome sequencing (WES) will be used to analyze gene mutations, such as single nucleotide variants (SNVs), copy number variants (CNVs), and fusion events. RNA-seq will be used to screen for differentially expressed genes (DEGs) and perform immunophenotyping, while multiplex immunohistochemistry will be employed to quantify the tumor immune microenvironment (TIME). The successful implementation of this project is expected to identify novel molecular biomarkers specific to the Chinese LSRCC population, enhance understanding of the unique immune phenotypes within this group, and-combined with clinical follow-up-establish correlations between molecular/immune signatures and therapeutic efficacy assessments, thereby providing evidence-based medical support for subsequent personalized precision diagnosis and treatment of LSRCC in this population.

Detailed description

This study aims to reveal the molecular characteristics and immune microenvironmental profile of signet ring cell carcinoma of the lung (LSRCC) in the Chinese population through integrated multi-omics analyses. The project plans to enroll formalin-fixed paraffin-embedded (FFPE) tissue samples and paired adjacent tissues from 39 patients with previously untreated LSRCC to establish a Chinese LSRCC molecular database. Whole-exome sequencing (WES) will be used to analyze gene mutations, including single nucleotide variants (SNVs), copy number variants (CNVs), and fusion events. RNA-seq will be utilized to screen for differentially expressed genes (DEGs) and conduct immunophenotyping, while multiplex immunohistochemistry will be applied to quantify the tumor immune microenvironment (TIME). The successful implementation of this project is expected to identify novel molecular biomarkers specific to the Chinese LSRCC population, enhance understanding of the unique immune phenotypes within this group, and-combined with clinical follow-up-establish correlations between molecular/immune signatures and therapeutic efficacy assessments, thereby providing evidence-based medical support for subsequent personalized precision diagnosis and treatment of LSRCC in this population.

Interventions

• Drug Patients with specific TIME subtype and ALK fusion mutations (confirmed via RNA-seq and OncoKB annotation) will receive tyrosine kinase inhibitors (TKIs, e.g., alectinib or crizotinib) as first-line
  Patients with specific TIME subtype and ALK fusion mutations (confirmed via RNA-seq and OncoKB annotation) will receive tyrosine kinase inhibitors (TKIs, e.g., alectinib or crizotinib) as first-line therapy. Clinical response will be assessed via RECIST v1.1 criteria using serial CT imaging (baseline, 8 weeks, and every 12 weeks thereafter). Correlative analyses will evaluate TKI efficacy in relation to TIME subtype, ALK fusion variant, and multi-omic signatures.

Primary outcome measures

• Week 8 Objective Response Rate (ORR) by RECIST v1.1 in ALK Fusion-Positive LSRCC Patients with Hybrid TIME Subtype [Time frame: 8 weeks]

Secondary outcome measures (6)

• Progression-Free Survival (PFS) [Time frame: From baseline until disease progression or death (assessed up to 24 months).]
• Overall Survival (OS) [Time frame: From baseline until death from any cause (assessed up to 36 months).]
• Duration of Response (DoR) [Time frame: From first response until progression or death (assessed up to 24 months).]
• Disease Control Rate (DCR) at Week 8 [Time frame: 8 weeks]
• Safety and Tolerability of TKI Therapy [Time frame: From initiation of TKI therapy until 30 days after the last dose (assessed up to 24 months).]
• Concordance Between Baseline mIHC-Defined TIME Subtypes and Treatment Outcomes [Time frame: From baseline until disease progression or death (assessed up to 24 months).]

Eligibility criteria

Inclusion criteria

1.Histologically confirmed, previously untreated LSRCC; 2. Adequate FFPE tumor tissue and paired adjacent non-tumor tissue available; 3. Expected survival ≥ 12 weeks; 4. Patients (or their legal guardians) willing and able to provide written informed consent; 5.Availability of complete pathology and imaging data.

Exclusion criteria

1\. Prior systemic anticancer therapy; 2. Secondary LSRCC (i.e., metastatic signet ring cell carcinoma originating from a non-lung primary site); 3. Concurrent other malignancies; 4. Incomplete pathology results, missing imaging data, or unreliable follow-up information; 5. Pregnancy or lactation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Centre of Translational Medicine, Affiliated Hangzhou First People's Hospital, Westlake Un — Hangzhou

Identifiers

NCT: NCT07207278 · 2025ZN214-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗