FHOD1 and FMNL1 formin proteins in intestinal gastric cancer: correlation with tumor-infiltrating T lymphocytes and molecular subtypes

Abstract

Background Gastric cancer (GC) is the third most common cause of cancer death. Intestinal type GC is a molecularly diverse disease. Formins control cytoskeletal processes and have been implicated in the progression of many cancers. Their clinical significance in GC remains unclear. Here, we characterize the expression of formin proteins FHOD1 and FMNL1 in intestinal GC tissue samples and investigate their association with clinical parameters, GC molecular subtypes and intratumoral T lymphocytes. Methods The prognostic significance of FHOD1 and FMNL1 mRNA expression was studied with Kaplan–Meier analyses in an online database. The expression of FHOD1 and FMNL1 proteins was characterized in GC cells, and in non-neoplastic and malignant tissues utilizing tumor microarrays of intestinal GC representing different molecular subtypes. FHOD1 and FMNL1 expression was correlated with clinical parameters, molecular features and T lymphocyte infiltration. Immunohistochemical expression of neither formin correlated with survival. Results Kaplan–Meier analysis associated high FHOD1 and FMNL1 mRNA expression with reduced overall survival (OS). Characterization of FHOD1 and FMNL1 in GC cells showed cytoplasmic expression along the actin filaments. Similar pattern was recapitulated in GC tissue samples. Elevated FMNL1 was associated with larger tumor size and higher disease stage. Downregulation of FHOD1 associated with TP53-mutated GC tumors. Tumor cell FHOD1 expression strongly correlated with high numbers of tumor-infiltrating CD8 + lymphocytes. Conclusions FHOD1 and FMNL1 proteins are expressed in the tumor cells of intestinal GC and significantly associate with clinical parameters without direct prognostic significance. FHOD1 correlates with high intratumoral CD8 + T lymphocyte infiltration in this cohort.

Pan‐cancer analysis revealing DAAM1 as a novel predictive biomarker for PD‐1/PD‐L1 blockade in clear cell renal cell carcinoma

“…An interesting research revealed that formin homology 2 domain containing 1 (FHOD1) and formin-like 1 (FMNL1), family members of Formin, are correlated with tumor-infiltrating lymphocytes in gastric cancer, which first linked Formin proteins with anti-tumor immunity. 10 However, molecular mechanisms underly Formin-mediated anti-tumor immunity have not been investigated, which is also a major shortcoming in the current research. However, the current research provides DAAM1 as a novel biomarker for PD-1/PD-L1 blockade in KIRC.…”