Person:

Gandhi, Leena

Background Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer. This study’s purpose was to determine the protein expression of collagen XXIII in tumor tissues from a variety of cancers and to assess collagen XXIII’s utility as a biomarker for non small-cell lung cancer (NSCLC).

Methods A multi-cancer tissue microarray (TMA) was used for immunohistochemical examination of collagen XXIII protein expression in a variety of cancers. Subsequently, collagen XXIII expression was analyzed in three separate cohorts using TMAs with representative tumor and control lung tissues from NSCLC patients. In addition, NSCLC patient urine samples were analyzed for the presence of collagen XXIII via Western blot.

Results Collagen XXIII was present in tissue samples from a variety of cancers. Within lung cancer tissues, collagen XXIII staining was enriched in NSCLC subtypes. Collagen XXIII was present in 294 of 333 (88%) lung adenocarcinomas and 97 of 133 (73%) squamous cell carcinomas (SqCC). In urine, collagen XXIII was present in 23 of 29 (79%) NSCLC patient samples but only in 15 of 54 (28%) control samples. High collagen XXIII staining intensity correlated with shorter recurrence-free survival in NSCLC patients.

Conclusions We demonstrate the capability of collagen XXIII as a tissue and urinary biomarker for NSCLC, where positivity in tissue or urine significantly correlates with presence of NSCLC and high staining intensity is a significant recurrence predictor.

Impact Inclusion of collagen XXIII in a tissue or urine-based cancer biomarker panel could inform NSCLC patient treatment decisions.

Non–small cell lung cancer (NSCLC) has a poor prognosis, with substantial mortality rates even among patients diagnosed with early-stage disease. There are few effective measures to block the development or progression of NSCLC. Antiangiogenic drugs represent a new class of agents targeting multiple aspects of tumor progression, including cell proliferation, invasion, migration, and outgrowth of metastatic deposits. We tested the multitargeted angiogenesis inhibitor sunitinib in a novel endogenous mouse model of NSCLC, which expresses a conditional activating mutation in Kras with or without conditional deletion of Lkb1; both alterations are frequent in human NSCLC. We showed that daily treatment with sunitinib reduced tumor size, caused tumor necrosis, blocked tumor progression, and prolonged median survival in both the metastatic (Lkb1/Kras) and nonmetastatic (Kras) mouse models; median survival was not reached in the nonmetastatic model after 1 year. However, the incidence of local and distant metastases was similar in sunitinib-treated and untreated Lkb1/Kras mice, suggesting that prolonged survival with sunitinib in these mice was due to direct effects on primary tumor growth rather than to inhibition of metastatic progression. These collective results suggest that the use of angiogenesis inhibitors in early-stage disease for prevention of tumor development and growth may have major survival benefits in the setting of NSCLC.