Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

Abstract

Background Squamous cell carcinomas of the lung are an extremely common and deadly form of non-small cell lung cancers. Clinical management of the disease is dependent on staging and metastatic status. Metastasis to the lymph node is especially crucial to diagnose as it occurs at an earlier stage. However, lymphadenectomies are invasive and tumor cells may be overlooked during evaluation.There are limited approved biomarkers for predicting lymph node metastasis with squamous cell carcinomas of the lung (LSCC). Methods Genome data of 60 tumor-adjacent samples were downloaded from Genome Expression Omnibus. We identified over-expressed HUB genes using Cytoscape as key prognostic markers. The selected markers were further evaluated based on gene ontology and overall expression levels compared to normal tissue using The Cancer Genome Atlas. We further validated these results using clinical biopsy tissue taken from squamous cell carcinoma patients. Results Analysis of the genome expression data resulted in 13 relevant hub genes that were differentially expressed in cancerous samples. All of these genes are associated with collagen biosynthesis within the tumor microenvironment. We chose Collagen Type 1 Alpha 1 (COL1A1) as the most relevant prognostic marker due to its high number of pathway connections and over expression in the tumor microenvironment compared to the other 12 genes. Additionally, based on analysis of The Cancer Genome Atlas, tumors with higher levels of COL1A1 expression are associated with poorer overall survival. Finally, evaluation of clinical biopsy samples suggests that overexpression of COL1A1 in the LSCC microenvironment highly correlates with lymph node metastasis. These results suggest COL1A1 is a clinically relevant marker that should be used to justify lymphadenectomies.

Deregulated glutamate to pro-collagen conversion is associated with adverse outcome in lung cancer and may be targeted by renin-angiotensin-aldosterone system (RAS) inhibition

“…Recently, a gene expression dataset analysis study highlighted the importance of collagen type 1 alpha 1 (COL1A1) in squamous cell lung cancer as COL1A1 was identified as a key marker of the squamous cell lung cancer microenvironment. Moreover increased COL1A1 expression was linked to shortened OS in the TCGA dataset [12]. An exploratory analysis of serum samples found increased levels Type XIX collagen in lung cancer patients compared to patients without pre-existing malignancies [13].…”

LncRNA LINC00511 promotes COL1A1-mediated proliferation and metastasis by sponging miR-126-5p/miR-218-5p in lung adenocarcinoma

“…Collagen type I alpha 1 chain (COL1A1) is confirmed to be an extracellular matrix protein that is overexpressed in many types of malignant tumors, including lung, breast, and colorectal tumors [ 18 – 20 ]. In addition, differential expression of COL1A1 predicts poor clinical outcomes (e.g., lymph node metastasis) in lung squamous cell carcinoma patients [ 21 ]. Thus, COL1A1 is considered a prognostic marker for lung tumors and a potential therapeutic target.…”

Tumor Nonimmune-Microenvironment-Related Gene Expression Signature Predicts Brain Metastasis in Lung Adenocarcinoma Patients after Surgery: A Machine Learning Approach Using Gene Expression Profiling

“…Bao et al reported that SPARC was a key mediator of the TGF-β signaling pathway and promoted invasion and metastasis of renal cell carcinoma [76]. In lung squamous cell carcinoma, COL1A1 overexpression in the microenvironment is highly correlated with lymph node metastasis [77]. SRPX2 promotes cell proliferation and metastasis in ESCC cells [78].…”