Table 3. Overview of the 9 genes showing consistent association with both PFS and OS (n = 51 patients with nsNSCLC).
| Gene | Known relationshipto ADC | Function (literature information) |
| Chromosome 16 openreading frame 89 (C16orf89) | Yes | Protein predominantly expressed in human thyroid tissue with specificity intermediate between TTFs and proteins involved in thyroid hormone synthesis [17] |
| Shows the same expression pattern as NKX2-1 [17] | ||
| Napsin A (NAPSA) | Yes | Gene for an aspartic peptidase, is considered as potential new biomarker for primary lung adenocarcinoma (more specific and sensitive than NKX2-1) [18]; clinical and pathological characteristics of napsin A-positive lung adenocarcinomas are similar to and overlap with those of NKX2-1 positive adenocarcinomas [19] |
| Surfactant protein B (SFTPB) | Yes | Hydrophobic protein, important for surfactant function and homeostasis [20] |
| SP-B mRNA detected in 53% of pulmonary adenocarcinomas with acinar, papillary, bronchioloalveolar, and solid growth patterns. SCLC, LSCLC, and non-pulmonary adenocarcinomas did not contain SP-B mRNA [20] | ||
| NKX2-1 is crucial for branching morphogenesis during normal lung development and transactivates the expression of the surfactant proteins such as SP-A, -B, and -C [21] | ||
| Aquaporin 4 (AQP4) | Yes | Potentially involved in lung cancer tumor cell extravasation and spread [22] |
| AQP4 expressed constitutively in 40% of all NSCLC carcinomas [23] | ||
| Higher transcript/protein levels of AQP4 in well-differentiated lung adenocarcinomas [23] suggesting association with favorable prognosis | ||
| Microarray summary data published which correlates with the SFTPB, NAPSA, and NKX2-1 genes [23] | ||
| TRAF2- and Nck-interactingkinase (TNIK) | No | Member of the germinal center kinase family; involved in cytoskeleton organization [24] |
| Emerging evidence indicating that TNIK is essential in activation of WNT pathway [25] | ||
| Lysophosphatidylcholine acyltransferase 1 (LPCAT1) | No | Expressed ubiquitously in almost all types of tissues, but is particularly high in surfactant-producing lung type II epithelial cells [26] |
| Interleukin 1 receptor,type II (IL1R2) | No | Unknown association with NSCLC |
| Acts as a negative and thus antiinflammatory regulator for IL-1, inhibits the activity of its ligands, no signaling [27] | ||
| Binds IL-1alpha, IL-1beta [28] | ||
| NK2 homeobox 1 (NKX2-1) | Yes | Gene for tissue-specific TTF-1, expressed mainly in the epithelial cells of the lungs and thyroid [29] |
| Implicated as contributing to lung cancer development [30] | ||
| Commonly used as marker for the diagnosis of primary and metastatic lung adenocarcinoma [29], [31] | ||
| Potential prognostic marker to explain the histotype-associated pemetrexed activity [32] | ||
| ABO glycosyl-transferase | No | Unknown association with NSCLC |
| Gene for ABO glycosyltransferase, catalyzes the transfer of carbohydrates to the H antigen, forming the antigenic structure of the ABO blood groups [33] |
Abbreviations: ADC, adenocarcinoma; IL, interleukin, LSCLC, large-cell lung cancer; mRNA, messenger ribonucleic acid; nsNSCLC, non-squamous non-small cell lung cancer; SCLC, small-cell lung cancer; SP-A/B/C, surfactant protein A/B/C; TTF-1, transcription factor 1.