TTF-1 and napsin A for lung adenocarcinoma, p40 for squamous lung cancer, GATA3 and mammaglobin for breast cancer, or synaptophysin and chromogranin A for neuroendocrine tumors).
Kaplan-Meier analysis showed that only tumor invasion status (IAD vs AIS/MIA, p = 0.003) could predict 5-year lung cancer-specific overall survival (LCS-OS), and IAD had a worse LCS-OS than AIS and MIA.
These results suggest that TP63rs7631358 G > A and CSF1R rs10079250 A > G may affect the prognosis of NSCLC in never-smoking females, as well as the risk of lung cancer.
Two single nucleotide polymorphisms (SNPs), rs6790167 (g243059A>G) in intron 9 of TP63 and rs1535045 (g6194C>T) in intron 1 of CD40 respectively, may affect the susceptibility of lung cancer.
To improve segregation between ADC and SqCC in small samples, the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm.
Our results, combined with those from previous studies, suggest that genetic variation in TP63 may influence lung cancer susceptibility in the Han population.
Among 16 SNPs, three SNPs (colony-stimulating factor 1 receptor [CSF1R] rs10079250A>G, tumor protein p63 [TP63] rs7631358G>A, and corepressor interacting with RBPJ 1 [CIR1] rs13009079T>C) were found to be significantly associated with lung cancer in the same direction as the discovery set.
Although p63 and its isoforms are overexpressed in a wide variety of human malignancies such as cervical, head and neck, and lung cancer, their role in endometrial carcinoma has not been investigated.
To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore.
The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).
The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).
The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively).
A common set of genes dysregulated in lung cancer was obtained, including BPA1, DUSP6, ASCL1, RNAS1 and S100P. p63 and CK 5/6 p63 are useful for differentiating adenocarcinoma and small cell lung cancer from squamous cell carcinoma.
Here, we tested whether genomic gains in six specific loci, TP63 on 3q28, EGFR on 7p12, MYC on 8q24, 5p15.2, and centromeric regions for chromosomes 3 (CEP3) and 6 (CEP6), may provide further value in the prediction of lung cancer.
Transient expression of p63 transactivated the maspin promoter with remarkable fold changes in cells expressing the TAp63, suggesting that TAp63 might be a novel stimulator of the maspin promoter in lung cancer.
These observations suggest that p63 genomic amplification has an early role in lung tumorigenesis and deserves additional evaluation as a biomarker for lung cancer progression.