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Transcriptomics Reveals Tissue-Agnostic Features in Adenocarcinomas, Squamous Cell Carcinomas

NEW YORK (GenomeWeb) – A University of Pennsylvania-led team has uncovered common transcriptomic features in adenocarcinomas and in squamous cell carcinomas that appear to be independent of the tumors' tissues of origin.

As they reported in PLOS Genetics, the researchers combined gene expression, non-coding RNA expression, methylation, and other data from nearly 1,500 adenocarcinoma or squamous cell carcinoma tumors considered for the Cancer Genome Atlas (TCGA) effort, including samples from individuals with esophageal, lung, or cervical cancer.

When the team searched for transcriptomic and methylation differences between adenocarcinomas and squamous cell carcinomas from the same parts of the body, it uncovered expression, methylation, and microRNA features that seemed to distinguish adenocarcinomas from squamous cell carcinomas. And based on the genes and pathways involved, the group got a glimpse at some of the potential drivers behind each histological type, along with information on patient outcomes.

"[U]tilizing pathway and survival analysis, we highlight common markers of [adenocarcinomas] that not only have prognostic value but may also have functional roles in tumorigenesis, thus serving as potential targets for broad therapeutic intervention," corresponding author and UPenn researcher Anil Rustgi and his co-authors wrote.

As tumors arising at a given body site may belong to different subtypes, the team suspected that transcriptomics-based comparisons across histologically distinct tumors from multiple tissue types might provide a clearer view of the molecular features marking adenocarcinomas and squamous cell carcinomas.

With that in mind, the researchers sought out representative tumor samples from body sites that are prone to developing tumors from both histological groups, compiling TCGA data for 80 esophageal adenocarcinomas, 81 esophageal squamous cell carcinomas, 533 adenocarcinomas of the lung, 502 lung squamous cell carcinomas, 44 cervical adenocarcinomas, and 254 squamous cell carcinomas occurring in the cervix.

"By focusing on organs in which both these subtypes arise, namely the esophagus, lung, and uterine cervix, we aimed to determine whether tissue of origin or another property, such as histology, contributes more significantly to observed variation in molecular signatures among tumors," the authors explained.

Through a series of comparisons using the lung and esophageal cancer samples, for example, the team found that expression-based clustering tended to bring together tumors from the same histological type. Meanwhile, the group's differential expression analyses led to expression shifts that were shared between adenocarcinomas at both body sites or across squamous cell carcinomas from both tissues.

The researchers noted that the 1,700 or so genes expressed at different levels in the adenocarcinomas and squamous cell carcinomas included genes with known ties to tumor development in each histological subtype. Likewise, the analysis unearthed methylation and miRNA shifts that were shared between histologically similar tumors from distinct tissues.

Along with experiments aimed at validating these findings in adenocarcinoma and squamous cell carcinoma samples from individuals with cervical cancer, the team went on to search for potential prognostic indicators in adenocarcinoma in particular. There, it narrowed in on 32 genes with expression patterns that coincided with survival time in lung and esophageal adenocarcinoma groups.

"Our analysis revealed an entire catalog of gene candidates for further study," the authors noted, "including those that correlate with survival outcomes, though an association with survival is not a prerequisite for being an effective target."