| Abstract: |
Proteins overexpressed in early-stage cancers may serve as early diagnosis and prognosis markers as well as targets for cancer therapies. In this study, we examined the expression of an essential amino acid carrier SLC7A5 (LAT1, CD98, or 4F2 light chain) in cancer tissue from two well-annotated cohorts of 575 cases of early-stage and 106 cases of late-stage colorectal cancer patients. Immunohistochemistry showed SLC7A5 overexpression in 72.0% of early-stage and 56.6% of late-stage cases. SLC7A5 expression was not influenced by patient gender, age, location, or mismatch repair status, although it appeared to be slightly less prevalent in tumors of mucinous differentiation or with lymphovascular invasion. Statistical analyses revealed a positive correlation between SLC7A5 overexpression and both overall survival and disease-free survival in early-stage but not late-stage cancers. Co-expression analyses of the TCGA and CPTAC colorectal cancer cohorts identified a network of gene transcripts positively related to SLC7A5, with its heterodimer partner SLC3A2 having the highest co-expression score. Network analysis uncovered the SLC7A network to be significantly associated with ncRNA such as tRNA processing and the mitotic cell cycle. Since SLC7A5 is also a marker of activated lymphocytes such as NK, T, and B lymphocytes, SLC7A5 overexpression in early colorectal cancers might trigger a strong anti-tumor immune response which could results in better clinical outcome. Overall, our study provides clear evidence of differential SLC7A5 expression and its prognostic value for early-stage colorectal cancer, although the understanding of its functions in colorectal tumorigenesis and cancer immunity is currently rather limited and awaits further characterization. © 2024 Ogawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: |
immunohistochemistry; cancer survival; controlled study; human tissue; protein expression; aged; aged, 80 and over; disease-free survival; middle aged; gene mutation; major clinical study; overall survival; sequence analysis; somatic mutation; genetics; disease free survival; cancer staging; neoplasm staging; colorectal cancer; cell proliferation; mitosis; tumor associated leukocyte; metabolism; gene; gene overexpression; gene expression; tumor differentiation; genetic transcription; pathology; tumor marker; histology; carcinogenesis; colorectal neoplasms; gene expression regulation; gene expression regulation, neoplastic; protein synthesis; colorectal tumor; mismatch repair; microsatellite instability; membrane protein; tumor immunity; tissue microarray; tumor growth; pik3ca gene; perineural invasion; braf gene; data visualization; diagnostic test accuracy study; clinical outcome; kras gene; cancer prognosis; rectum mucosa; very elderly; humans; prognosis; human; male; female; article; amino acid transporter; biomarkers, tumor; gene network analysis; fusion regulatory protein 1, heavy chain; large neutral amino acid-transporter 1; excitatory amino acid transporter; cd98 antigen; slc3a2 protein, human; slc7a5 protein, human; slc7a5 gene; weighted gene co expression network analysis
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