Galectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer

Abstract

Approximately 30–40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profiling in a retrospective study using frozen and paraffin embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confined to galectin-1, -3, -4, -7, -8, and -9. Next to stage, univariable Cox regression analysis identified galectin-1, galectin-9FL and galectin-9Δ5 as possible prognostic markers. Kaplan-Meier survival estimates revealed that overall survival was significantly shorter in patients that express galectin-1 above median levels, i.e., 23.0 (2.9–43.1) vs. 59.9 (47.7–72.1) months (p = 0.020) as well as in patients that express galectin-9Δ5 or galectin-9FL below the median, resp. 59.9 (41.9–75.9) vs. 32.8 (8.7–56.9) months (p = 0.014) or 23.2 (−0.4–46.8) vs. 58.9 (42.9–74.9) months (p = 0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most significant prognostic model included stage, age, gal-1 and gal-9Δ5 while the model for DFS included stage, age and gal-9Δ5. In conclusion, the current study confirms the prognostic value of galectin-1 and identifies galectin-9Δ5 as novel potential prognostic markers in early stage NSCLC. These findings could help to identify early stage NSCLC patients that might benefit most from adjuvant chemotherapy.

Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer

“…The involvement of galectins in different processes of tumor progression is supported by reports that altered galectin expression has diagnostic or prognostic value in different cancer types including ovarian, prostate, breast, head and neck and non-small cell lung cancer [17–26]. In squamous cervical cancer patients who received radiation therapy, a recent study reported that expression of galectin-1 by the tumor was an independent predictor for local recurrence and poor survival [27].…”

A key role for galectin‐1 in sprouting angiogenesis revealed by novel rationally designed antibodies

“…Obviously, such valuable information is not obtained by analysis of gene expression at the mRNA level. On the other hand, single nucleotide polymorphisms as well as alternative splice variants of specific galectins have also been associated with prognosis . Such variations are not always detected by the currently available antibodies, an observation that indicates the relevance of combining both genomic and proteomic information.…”

“…Moreover, deregulated expression or function of galectin‐1 is frequently associated with disease, most notably with inflammatory disorders and cancer . Regarding the latter, we and others have shown that increased galectin‐1 expression is associated with poor survival in many cancer types . This has been attributed to the capacity of galectin‐1 to suppress the anti‐tumor immune response, to induce tumor angiogenesis, and to promote tumor metastasis .…”

“…Quantitative PCR (qPCR) was performed as described previously on a CFX96 Real‐time PCR detection system (Bio‐Rad). Threshold cycle (Ct) values were normalized to three reference genes and relative expression is expressed as 2 −δCt …”

“…10,11 Regarding the latter, we and others have shown that increased galectin-1 expression is associated with poor survival in many cancer types. [11][12][13] This has been attributed to the capacity of galectin-1 to suppress the anti-tumor immune response, 14,15 to induce tumor angiogenesis, 16,17 and to promote tumor metastasis. 18,19 Given these tumor-promoting activities, galectin-1 is considered a potential target for cancer therapy.…”