Initial evidence for Sec62 as a prognostic marker in advanced head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with an increasing incidence. To aid with the selection of the most appropriate therapy, biomarkers have become a specific research focus. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer. In addition, Sec62 may be a promising candidate in HNSCC. Pretreatment biopsies of 35 patients with locally advanced HNSCC, who were treated with definitive chemoradiation therapy without prior surgery, were examined for the expression of Sec62 protein, as well as the expression of epidermal growth factor receptor (EGFR), p16 and survivin proteins. Immunohistological results were correlated with patient overall survival (OS) and progression-free survival (PFS) times. In the present patient cohort, 12/35 cases (34%) demonstrated strong and 8/35 cases (23%) moderate Sec62 staining intensity. Additionally, in 11/35 cases (31%), weak staining was observed, and only 4/35 cases (11%) were Sec62-negative. Notably, a high Sec62 protein level was associated with a significantly poorer OS and PFS (P=0.020 and P=0.028, respectively). Furthermore, higher nuclear survivin expression showed a weak trend for poorer OS rate (P=0.079), whilst neither cytoplasmic survivin, EGFR nor p16 influenced OS or PFS significantly. The present study indicated that Sec62 is a promising prognostic marker for HNSCC. Increased Sec62 protein expression may indicate a poorer prognosis in advanced HNSCC. As the present study was focused on patients treated by chemoradiation therapy, further studies with larger patient cohorts and alternative treatment approaches are required in order to define the prognostic value of Sec62 in HNSCC.

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas

“…These data were strongly consistent with previous studies focused on the expression of SEC62 [27] and SOX2 [30, 35] in healthy and cancerous tissue of the head and neck region and consistently showed an overexpression of both genes in HNSCC tissue.…”

“…For SEC62 , these data confirmed our previously reported findings for a smaller cohort of HNSCC patients, in which we analyzed SEC62 expression in tissue specimens of the primary tumor [27]. For SOX2 , some studies were consistent with our results and reported a better outcome of HNSCC patients with high SOX2 expression levels in the primary tumor [42, 48, 49].…”

Selective Autophagy of the Protein Homeostasis Machinery: Ribophagy, Proteaphagy and ER-Phagy

“…Other protein substrates, including ERAD proteins, are degraded independently of SEC62 function. Moreover, SEC62 has been found to be upregulated in several types of cancer, where it is associated with increased metastatic and invasive potential, as well as higher ER stress tolerance (Greiner et al, 2011a,b;Wemmert et al, 2016). Whether SEC62's role in re-establishing basic ER physiology via degradation of UPR proteins is related to its role in tumorigenesis remains an area for further investigation.…”

ER-phagy at a glance

“…By contrast, it has a tumor-suppressive function in colon and breast cancer that is well established (Islam et al, 2017;Tang et al, 2007). SEC62 is also amplified in several cancers with a yet undefined molecular role (Hagerstrand et al, 2013;Wemmert et al, 2016). Because a well-established function of SEC62 is to resolve ER stress, it is important to emphasize that the UPR has a dual impact on tumors: it can support cancer cell growth, providing a machinery to deal with stress, but, on the other hand, it can have a cytotoxic effect and induce cell death via apoptosis.…”