Genetic Impact of HOTAIR, LINC00951, POLR2E and HULC Polymorphisms in Histopathological and Laboratory Prognostic Factors in Esophageal Cancer in the West: A Case-Control Study

Simple Summary Single-Nucleotide-Polymorphisms in long non-coding RNAs are correlated with esophageal carcinogenesis, yet research remains restricted in Asian ethnicities. Herein, FFPE specimens were obtained from surgically treated esophageal cancer patients for genotyping deriving from European ancestry. HULC rs7763881 polymorphism was not associated with cancer predisposition. LINC00951 rs11752942 was underrepresented in Ca19.9 elevated subgroup. HOTAIR rs920778 was more frequent in both worse differentiation grade and positive Signet Ring Cell and Ca19.9 subgroups. POLR2E rs3787016 was identified less frequently in Adenocarcinoma, Signet Ring Cell, and Diffuse histological subtypes, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was found more often in CEA positive subgroup of the whole cancer cohort. Taken together, these lncRNAs polymorphisms are promising not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk and oncological outcomes including survival.Abstract Long non-coding RNAs' HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016, and HULC rs7763881 are progressively reported having a close genetic affinity with esophageal carcinogenesis in the East. Nonetheless, their correlation with variables already endorsed as significant prognostic factors in terms of staging, guiding treatment and predicting recurrence, metastasis, and survival have yet to be explored. Herein, we investigated their prognostic value by correlating them with clinicopathological and laboratory prognostic markers in esophageal cancer in the West. Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated on for esophageal cancer between 2014 and 2018 were compared with 121 healthy community controls. HULC was not detected differently in any of the cancer prognostic subgroups. LINC00951 was underrepresented in Ca19.9 elevated subgroup. HOTAIR was more frequent in both worse differentiation grade and positive Signet-Ring-Cell and Ca19.9 subgroups. POLR2E was identified less frequently in Adenocarcinoma, Signet-Ring-Cell, and Diffuse histologies, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was overrepresented in CEA positive subgroup. These lncRNAs polymorphisms may hold great potential not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk, clinical outcome, and survival. Clinical implications of these findings need to be validated with prospective larger sample-size studies.