C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

Figure 1 Structure and expression of the protein C4. 4A. A: Schematic outline of the gene cluster encompassing multidomain members of the LU protein family, highlighting the gene encoding C4.4A (LYPD3) and its exon composition. Modified from Kriegbaum et al^[20,24], 2011 and Jacobsen et al^[20,24]; B: Cartoon of the structure of C4.4A. The insert represents the three-finger fold characteristic of LU domains (made in PyMOL, DeLano Scientific, using PDB coordinates 1NEA). Modified from Hansen et al^[19]; C and D: C4.4A expression in suprabasal layers of squamous epithelium, exemplified by tissue-engineered human epidermis (C) and the transition between the glandular and non-glandular portions of the rodent stomach (D). C4.4A is detected by a polyclonal C4.4A antibody and visualized by NovaRED chromogen. D is reproduced with permission from BestPractice Onkologi, Denmark^[89].

Figure 2 C4. 4A in pulmonary squamous cell carcinoma. Panels A-E: C4.4A expression as detected by immunohistochemistry with a polyclonal antibody in normal bronchial epithelium (A), hyperplasia (B), metaplasia (C), dysplasia (D) and invasive squamous cell carcinoma (SCC) (E). A, B, D and C, E are reproduced with permission from Jacobsen et al^[34], 2012 and BestPractice Onkologi, Denmark^[89], respectively. Panel F: Kaplan-Meier curves for the survival of SCC patients, which is independent of C4.4A scores, here stratified by tertiles (red: Lowest level of C4.4A; blue: Intermediate level of C4.4A; green: Highest level of C4.4A). Modified from Jacobsen et al^[33], 2013.

Figure 3 C4. 4A in pulmonary adenocarcinoma. Panels A-E: C4.4A expression as detected by immunohistochemistry with a polyclonal antibody in normal alveoli (A; reproduced with permission from Jacobsen et al[34], 2012), atypical adenomatous hyperplasia (B), invasive AC with predominant mucinous lepidic (C), non-mucinous lepidic (D), acinar (E), papillary (F) and solid (G) pattern. Panel H: Kaplan-Meier estimates for the survival of AC patients, which is correlated with C4.4A scores, here stratified by tertiles (red: Lowest level of C4.4A; blue: Intermediate level of C4.4A; green: Highest level of C4.4A). Modified from Jacobsen et al^[33], 2013.