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

N/ARecruitingNCT07207278

First People's Hospital of Hangzhou39 enrolled

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.

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.

Study Type

OBSERVATIONAL

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Week 8 Objective Response Rate (ORR) by RECIST v1.1 in ALK Fusion-Positive LSRCC Patients with Hybrid TIME Subtype

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.

Time frame: 8 weeks

Secondary Outcomes

Progression-Free Survival (PFS)

Time from initiation of TKI therapy to the first documented radiologic disease progression (as per RECIST v1.1) or death from any cause, whichever occurs first.

Time frame: From baseline until disease progression or death (assessed up to 24 months).

Overall Survival (OS)

Time from initiation of TKI therapy to death from any cause.

Time frame: From baseline until death from any cause (assessed up to 36 months).

Duration of Response (DoR)

Among patients who achieve an objective response (CR or PR), the time from the first documented response to disease progression or death from any cause.

Time frame: From first response until progression or death (assessed up to 24 months).

Disease Control Rate (DCR) at Week 8

Proportion of patients achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1 at Week 8.

Time frame: 8 weeks

Safety and Tolerability of TKI Therapy

Incidence and severity of adverse events, laboratory abnormalities, and dose modifications, graded according to NCI-CTCAE version 5.0.

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

Agreement between baseline multiplex immunohistochemistry (mIHC)-defined TIME subtypes (I, II, III) and real-world treatment outcomes (ORR and PFS) across the full cohort.