Nuzhat Sial,1 Saba Saeed,2 Mukhtiar Ahmad,3 Yasir Hameed,3 Abdul Rehman,4 Mustansar Abbas,5 Rizwan Asif,6 Hamad Ahmed,5 Muhammad Safdar Hussain,3 Jalil Ur Rehman,7 Muhammad Atif,7 Muhammad Rashid Khan8 1Department of Zoology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Zoology, University of the Punjab, Lahore, Pakistan; 3Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 4Department of Eastern Medicine, Qarshi University, Lahore, Pakistan; 5Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan; 6Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 7University College of Conventional Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 8University College of Eastern Medicine, The Islamia University of Bahawalpur, Bahawalpur, PakistanCorrespondence: Yasir HameedDepartment of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, 63100, PakistanEmail Yasirhameed2011@gmail.comIntroduction: Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered.Methods: In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan–Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD.Results: In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level.Conclusion: In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.Keywords: TMED2, cancer, expression variations, biomarker