Sialic acids in gynecological cancer development and progression: Impact on diagnosis and treatment

Abstract

Gynecological cancers are in the top 10 of most common cancers in women. Survival and outcome are strongly related to the stage at diagnosis. Therefore, early diagnosis is essential in reducing morbidity and mortality. The high mortality rate of gynecological cancers can mainly be attributed to ovarian cancer (OC). OC is commonly diagnosed at an advanced stage due to a lack of proper screening tools allowing early detection. Endometrial cancer (EC) on the contrary, is mostly diagnosed at an early stage and has, in general, better outcomes. The incidence of nonendometrioid EC has increased in the last decade, displaying a shared tumor biology with OC and consequently significantly worse outcome. New approaches allowing detection of gynecological cancers in an early stage are therefore desired. Recent studies on cancer biology have shown the relevance of altered glycosylation in the occurrence and progression of cancer. The aberrant expression of sialic acid, a specific carbohydrate terminating glycoproteins and glycolipids on the cell‐surface, is frequently correlated with malignancy. We aimed to determine the current understanding of sialic acid function in different gynecological cancers to identify the gaps in knowledge and its potential use for new diagnostic and therapeutic avenues. Therefore we performed a review on current literature focusing on studies where sialylation was linked to gynecological cancers. The identified studies showed elevated levels of sialic acid in serum, tissue and sialylated antigens in most patients with gynecological cancers, underlining its potential for diagnosis.

The Prognostic Value of Serum Sialic Acid in Patients with Nasopharyngeal Carcinoma: A Propensity Score Matching Study

“…22 It participates in the reprogrammed metabolisms of cancer cells, thus affecting cell adhesion, intercellular communication, and contact inhibition. 14,21 Under normal circumstances, the serum SA level remains stable. However, when cells undergo malignant transformation, SA is shed from the cell surface and circulates in the bloodstream as serum 23 In malignant tumor cells, there is an increase in SA synthesis metabolism, known as hypersialylation, which promotes tumor progression.…”

“…Our study showed that the high SA group had a lower LRRFS, DMFS, PFS, and OS, indicating that increased SA is a poor prognostic factor for tumors, correlating with the clinical activity of the disease, similar to conclusions from studies conducted on many cancer types. [13][14][15]25,26 Research has also shown that SA levels were higher in the group of patients with metastatic breast cancer compared to those with non-metastatic breast cancer. 27 Currently, chemoradiotherapy is the preferred treatment modality for NPC.…”

“… 13 In gynecological malignancies, including ovarian, endometrial, and cervical cancers, increased SA expression has been associated with more advanced disease stages and poorer prognosis. 14 Furthermore, higher serum SA levels have been linked to poorer survival in G3 gastric neuroendocrine neoplasms. 15 Currently, there is no existing research investigating the relationship between SA prior to treatment and the prognosis of NPC.…”

Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers

“…Targeting OC is of particular importance since patients with OC are reported to have significantly enhanced level of the total sialylation (α2,3-/ α2,6-linked Sia). The bi-and trisialylated highly branched glycans exhibit low expression in healthy individual, whereas they are reported to be overexpressed in patients with OC (14)(15)(16). The interaction between Siglec-7 and its ligands has been reported to play a role in the inhibition of NK-mediated antitumor toxicity (7).…”

Clinical value of quantitative analysis of contrast-enhanced ultrasonography in the differential diagnosis of benign and malignant pelvic tumors

“…Among pelvic tumors, cervical cancer, endometrial cancer, and ovarian cancer are among the top 10 most common cancers in women ( 1 ). Among these, ovarian cancer is considered to be a “silent killer”, as most patients present with few symptoms or are diagnosed at the advanced stages (III and IV) ( 2 , 3 ).…”