Published online Oct 10, 2014. doi: 10.5306/wjco.v5.i4.621
Revised: June 4, 2014
Accepted: June 14, 2014
Published online: October 10, 2014
Processing time: 209 Days and 15.1 Hours
The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uPAR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasive carcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.
Core tip: C4.4A is a new biomarker with potential prognostic value in pulmonary adenocarcinoma. High levels of protein expression correlate with poor patient survival and a histological growth pattern of the solid type. Recent data suggest that C4.4A is negatively regulated by the tumor suppressor liver kinase B1 (LKB1), which is inactivated in a fraction of adenocarcinomas of the lung. Such an inverse association between C4.4A and LKB1 could possibly render C4.4A a candidate predictive biomarker for therapeutic intervention targeting components of the LKB1 pathway, such as mammalian target of rapamycin.