Molecular evolution of intestinal-type early gastric cancer according to Correa cascade.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages.

Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy.

Background: A minority of patients with extensive-stage small cell lung cancer (ES-SCLC) exhibit prolonged survival following first-line chemoimmunotherapy, which warrants the use of reliable biomarkers. Here, we investigated the disparities in genomics and immune cell spatial distribution between long- and short-term survival of patients with ES-SCLC.

Methods: We retrospectively recruited 11 long-term (>2 years) and 13 short-term (<9 months) ES-SCLC survivors receiving first-line chemoimmunotherapy.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness.

Multidimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer.

Colorectal cancer is frequently diagnosed in advanced stages, highlighting the need for developing approaches for early detection. Liquid biopsy using cell-free DNA (cfDNA) fragmentomics is a promising approach, but the clinical application is hindered by complexity and cost. This study aimed to develop an integrated model using cfDNA fragmentomics for accurate, cost-effective early-stage colorectal cancer detection.

Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma.

Background: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.

Methods: We conducted a single-center, open-label, single-arm, phase II study.

Molecular characteristics of early-onset compared with late-onset colorectal cancer: a case controlled study.

Background: Early-onset colorectal cancer (EOCRC) is associated with a poorer prognosis relative to late-onset colorectal cancer (LOCRC), and its incidence has witnessed a gradual escalation in recent years. This necessitates a comprehensive examination of the underlying pathogenesis and the identification of therapeutic targets specific to EOCRC patients. The present study aimed to delineate the distinct molecular landscape of EOCRC by juxtaposing it with that of LOCRC.

Mutations and High Prevalence of dMMR-associated Mutational Signatures as Prognostic Indicators in Metastatic Colorectal Cancer.

The conventional treatment strategies for patients with metastatic colorectal cancer (mCRC) are predominantly guided by the status of RAS and BRAF mutations. Although patients may exhibit analogous pathological characteristics and undergo similar treatment regimens, notable disparities in their prognostic outcomes can be observed. Therefore, tissue and plasma samples from 40 mCRC patients underwent next-generation sequencing targeting 425 cancer-relevant genes.

Case Report: Cancer spectrum and genetic characteristics of a germline p.L606M variant-induced polyposis syndrome.

Germline variations in the DNA polymerase genes, and , can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In this report, we present the case of a 22-year-old female patient who had been diagnosed with gastrointestinal polyposis, breast fibroadenoma, multiple primary colorectal cancers, and glioblastoma (grade IV) within a span of 4 years.

RB1 aberrations predict outcomes of immune checkpoint inhibitor combination therapy in NSCLC.

Introduction: Immune checkpoint inhibitors (ICI) have changed the treatment of non-small cell lung cancer (NSCLC). Furthermore, compared with monotherapy, ICI combination therapy had better efficacy and partly different mechanism. Therefore, we aim to investigate and improve biomarkers specialized for ICI combination therapy.

Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution.

Background: Lung cancer is the deadliest and most diagnosed type of cancer worldwide. The 5-year survival rate of lung adenocarcinoma (LUAD) dropped significantly when tumor stages advanced. Patients who received surgically resecting at the pre-invasive stage had a 5-year survival rate of nearly 100%.

Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial.

Background: The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China.

Methods: This was an open-label, single-arm, phase 2 trial.

Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

Background: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies.

Spectrum and tissue distribution of RB1 pathogenic alleles in mosaic retinoblastoma patients.

To characterize the spectrum of mosaic RB1 pathogenic alleles and map the distribution of mutant cells in available tissues from mosaic patients. Next-generation sequencing was performed on blood samples from 263 retinoblastoma families to identify mosaic RB1 variant alleles. A variety of available tissues were sampled to determine tissue distribution and fraction of mutant cells in five mosaic patients who consented to participate in mosaic pathogenic allele research.

Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer.

Background: Neoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients' genomic characteristics.

Methods: We prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery.

Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma.

Background: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histological subtype with unique clinical and pathological features. Despite previous genomic studies on lung IMA, the genetic characteristics and the prognosis-related biomarkers in Chinese surgically resected lung IMA remain unclear.

Methods: We collected 76 surgically resected primary tumors of invasive lung adenocarcinoma, including 51 IMA and 25 non-mucinous adenocarcinomas (non-IMA).

Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors.

EGFR exon 20 insertions (EGFR e20ins) account for up to 10% of EGFR mutations in lung cancer; however, tumors with EGFR e20ins had poor response rates to EGFR tyrosine kinase inhibitors (TKIs) including gefitinib, erlotinib, afatinib, and osimertinib, and the heterogeneity of EGFR e20ins further complicates the clinical studies. Here, we retrospectively screened next-generation sequencing (NGS) data from 24 468 lung cancer patients, and a total of 85 unique EGFR e20ins variants were identified in 547 cases (2.24%), with p.

Comprehensive Genomic Profiling Identifies Novel Genetic Predictors of Response to Anti-PD-(L)1 Therapies in Non-Small Cell Lung Cancer.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized cancer management. However, molecular determinants of response to ICIs remain incompletely understood.

Experimental Design: We performed genomic profiling of 78 patients with non-small cell lung cancer (NSCLC) who underwent anti-PD-(L)1 therapies by both whole-exome and targeted next-generation sequencing (a 422-cancer-gene panel) to explore the predictive biomarkers of ICI response.