Multi Omics Molecular Characteristics and Immunophenotyping of Lung Signet Ring Cell Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Week 8 Objective Response Rate (ORR) by RECIST v1.1 in ALK Fusion-Positive LSRCC Patients with Hybrid TIME Subtype
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Histologically confirmed, previously untreated LSRCC;
- •Adequate FFPE tumor tissue and paired adjacent non-tumor tissue available;
- •Expected survival ≥ 12 weeks;
- •Patients (or their legal guardians) willing and able to provide written informed consent; 5.Availability of complete pathology and imaging data.
排除标准
- •1. Prior systemic anticancer therapy;
- •Secondary LSRCC (i.e., metastatic signet ring cell carcinoma originating from a non-lung primary site);
- •Concurrent other malignancies;
- •Incomplete pathology results, missing imaging data, or unreliable follow-up information;
- •Pregnancy or lactation
研究组 & 干预措施
Chinese LSRCC Multi-omics Cohort
This cohort comprises 39 treatment-naïve patients with histopathologically confirmed lung signet ring cell carcinoma (LSRCC) enrolled across multiple medical centers in China. Key molecular features include frequent mutations in core genes, distinct copy number variations (CNVs), and transcriptional up- and down-regulation of novel biomarkers. Tumor immune microenvironment (TIME) profiling classified patients into three subtypes: I, II, and III.
干预措施: 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 (Drug)
结局指标
主要结局
Week 8 Objective Response Rate (ORR) by RECIST v1.1 in ALK Fusion-Positive LSRCC Patients with Hybrid TIME Subtype
时间窗: 8 weeks
Objective Response Rate (ORR), defined as the proportion of patients achieving Complete Response (CR) or Partial Response (PR) per RECIST v1.1 criteria, assessed via contrast-enhanced CT at Week 8 following initiation of TKI therapy.
次要结局
- Progression-Free Survival (PFS)(From baseline until disease progression or death (assessed up to 24 months).)
- Overall Survival (OS)(From baseline until death from any cause (assessed up to 36 months).)
- Duration of Response (DoR)(From first response until progression or death (assessed up to 24 months).)
- Disease Control Rate (DCR) at Week 8(8 weeks)
- Safety and Tolerability of TKI Therapy(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(From baseline until disease progression or death (assessed up to 24 months).)