Transcriptomic Architecture of the Adjacent Airway Field Cancerization in Non–Small Cell Lung Cancer

Abstract

The adjacent airway FC comprises both site-independent profiles as well as gradient and localized airway expression patterns. Profiling of the airway FC may provide new insights into NSCLC oncogenesis and molecular tools for detection of the disease.

Early Events in the Molecular Pathogenesis of Lung Cancer

“…Various studies have suggested that adjacent normal-appearing airway epithelia exhibit molecular alterations that are characteristic of the nearby lung tumor, an effect referred to by our group and others as the molecular and adjacent airway field of cancerization (14,96,97). As mentioned before, detailed analysis of histologically normal, premalignant, and malignant epithelia from LUSC patients revealed that multiple, sequentially occurring allelic imbalance events such as LOH commence in clonally independent foci early in the multistage pathogenesis of LUSC (22,61).…”

“…These findings suggest that the airway field of injury exhibits temporal molecular changes that may be associated with lung cancer recurrence in surgically treated early stage patients (96). In another study by the same group, paired NSCLCs, uninvolved normal lung tissues and multiple normal-appearing airways in the adjacent field of cancerization were analyzed by whole-transcriptome profiling (97). Importantly, the study demonstrated that gene expression patterns in the adjacent airway field of cancerization were enriched with a signature that can distinguish smokers with lung cancer from smokers with benign disease (97).…”

“…In another study by the same group, paired NSCLCs, uninvolved normal lung tissues and multiple normal-appearing airways in the adjacent field of cancerization were analyzed by whole-transcriptome profiling (97). Importantly, the study demonstrated that gene expression patterns in the adjacent airway field of cancerization were enriched with a signature that can distinguish smokers with lung cancer from smokers with benign disease (97). This study also identified notable spatial properties in the airway field of cancerization in which gene profiles of adjacent but not distant airway cells closely embodied expression patterns of the nearby NSCLC (97).…”

Molecular alterations in the carcinogenesis and progression of hepatocellular carcinoma: Tumor factors and background liver factors

“…Previous studies have also investigated the background tissues of numerous other malignancies (120)(121)(122). Yoshida et al (120) examined the methylation status of CpG islands in the promoter regions of six genes and two repetitive DNA elements in the gastric mucosae, and revealed that the methylation levels were consistently increased in a stepwise manner with activity of gastric inflammation, among patients who were H. pylori-negative, or had low-or high-titers (120), and concluded that evaluating DNA methylation levels in the gastric mucosae may predict the risk of gastric cancer.…”

“…Lee et al (121) evaluated promoter region methylation of the cadherin 1 (CDH1) gene in the non-neoplastic mucosae of diffuse gastric cancer and revealed there was a significantly higher methylation ratio, compared with normal non-cancerous gastric mucosae. Kadara et al (122) compared the gene expression profiles in non-small cell lung cancer airway tissues at various distances from the tumor tissues and normal lung tissues (122); significantly higher levels of lysosomal protein transmembrane 4β (LAPTM4B) mRNA transcripts were identified in the airway tissues near tumors. These attempts to clarify the molecular changes in non-cancerous tissues in several kinds of cancers are similar in concept to the evaluation of molecules in background liver of HCC.…”