Related Experiment Video

Updated: Jun 17, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.2K

PPIC-labeled CAFs: Key players in neoadjuvant chemotherapy resistance for gastric cancer

Honghao Yin1, Lili Sun2, Yuan Yuan1

  • 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, The First Hospital of China Medical University, Shenyang, China.

Translational Oncology
|August 8, 2024
PubMed
Abstract

Insights

Specific cancer-associated fibroblast (CAF) subgroups, identified by PPIC expression, are linked to neoadjuvant chemotherapy (NCT) resistance in gastric cancer (GC). This finding offers potential new targets for overcoming drug resistance in GC patients.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Gastric cancer (GC) is a leading cause of cancer mortality, with advanced stages showing poor survival.
  • Neoadjuvant chemotherapy (NCT) is crucial for GC treatment but is often hindered by drug resistance.
  • Cancer-associated fibroblasts (CAFs) contribute to GC drug resistance, yet specific CAF subpopulations involved remain unclear.

Purpose of the Study:

  • To identify specific cancer-associated fibroblast (CAF) subpopulations that contribute to neoadjuvant chemotherapy (NCT) resistance in gastric cancer (GC).
  • To investigate the role of the PPIC gene and its encoded protein, cyclophilin C (CypC), in GC chemoresistance.

Main Methods:

  • Differential gene expression analysis (GEO2R) to compare chemosensitive and resistant GC patients.
  • Single-cell RNA sequencing (scRNA-seq) to identify CAF-related genes.
  • Immunohistochemistry to validate key gene expression (CypC) in GC tissues and correlate with treatment response and clinical features.

Main Results:

  • The gene PPIC, highly expressed in CAFs, was significantly associated with NCT resistance in GC.
  • Cyclophilin C (CypC) expression was higher in resistant GC tissues compared to sensitive ones (69.7% vs. 43.6%).
  • High CAF CypC expression correlated with larger tumor size, advanced T and TNM stages, and vascular invasion, but not overall survival (OS).

Conclusions:

  • PPIC-labeled CAF subgroups are implicated in GC chemoresistance and poorer prognosis.
  • These CAF subgroups may induce drug resistance via pathways like glucose metabolism and extracellular matrix remodeling.
  • Further research is needed to elucidate the precise mechanisms of PPIC-labeled CAFs in GC drug resistance.
Keywords:
CAFChemoresistanceCypCGastric cancerImmune microenvironmentPPIC

More Related Videos

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

652
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT10:28

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT

Published on: January 22, 2018

11.1K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.5K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
156