Cytoplasmic Collagen Xi?i As A Prognostic Biomarker In Esophageal Squamous Cell Carcinoma

ESCC is broadly pervaded in east Asia and serves as the most common variant of esophageal cancer in China.Regardless of highly evolutive therapies comprising endoscopic resection and ablation,surgery and neoadjuvant chemoradiotherapy,ESCC remains a devastating 5-year survival rate.Advanced stage at initial diagnosis due to dormant clinical manifestation is the primary cause in contribution to the grim outcome.Besides,dysregulation of oncogenes and tumor suppressor genes reinforces lethality of ESCC.Digging of somatic genomic alternations and underlying mechanisms is urgently required.Collagens,a family of 28 members,is the main structural protein of the extracellular matrix consisting of three subtypes,namely fibrillar collagens,non-fibril forming collagens,and fibril-associated collagens.Collagen XI,a minor fibrillar collagen found in many tissues,is mostly detected in cartilage.It is a heterotrimeric protein composed of three ?chains.Both ?I and ?II are genetically diverse,and ?III is a hyperglycosylated version of collagen II?I.Stromal/cytoplasmic collagenXI?I(COL11A1)has been highlighted in the process of neoplastic transformation,including epithelial mesenchymal transition(EMT),metastasis and invasiveness.Whereas the biological role and clinical significance of COL11A1 in ESCC remain sealed.We investigated COL11A1 expression in 16 pairs of ESCC and adjacent normal tissues by RT-PCR and western blotting analysis.Correlations of COL11A1 expression with clinicopathologic parameters and survival status were then determined by immunohistochemistry in 116 ESCC and 50 normal specimens.Furthermore,bioinformatics was used for mechanisms exploration.And in vitro knockdown experiments were also performed.We found that COL11A1 expression was significantly higher in ESCC than in paired normal tissues at both mRNA and protein level.Immunohistochemistry showed that COL11A1 was predominantly localized to the cytoplasm rather than tumor stroma,patients with high COL11A1 expression had a poorer overall survival rate than those with low COL11A1 expression.Besides,increased COL11A1 expression was dramatically correlated with advanced clinical stage,invasion depth and lymph node metastases and served as an independent prognostic marker for ESCC.Likewise,COL11A1 dependent nomogram predicted a more precise survival outcome than traditional staging system.Moreover,COL11A1 silencing resulted in impaired cell proliferation and EMT,and subdued EMT inhibited cells aggressiveness.These biological processes might bemodulated by COL11A1 via the intracellular AKT/ERK/c-Myc cascades.