Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer

Sharia Hernandez, Prajnan Das, Emma B. Holliday, Li Shen, Wei Lu, Benny Johnson, Craig A. Messick, Cullen M. Taniguchi, John Skibber, Ethan B. Ludmir, Y. Nancy You, Grace Li Smith, Brian Bednarski, Larisa Kostousov, Eugene J. Koay, Bruce D. Minsky, Matthew Tillman, Shaelynn Portier, Cathy Eng, Albert C. KoongGeorge J. Chang, Wai Chin Foo, Jing Wang, Luisa Solis Soto, Van K. Morris

Research output: Contribution to journalArticlepeer-review


The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA.

Original languageEnglish (US)
Article number1701
Issue number6
StatePublished - Mar 10 2023


  • chemoradiation
  • digital spatial profiling
  • protein profiling
  • recurrence
  • squamous anal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer'. Together they form a unique fingerprint.

Cite this