Prognostic factors in endometrial cancer

Endometrial cancer (EC) is the most common malignancy of the female reproductive system in Sweden. Patients with EC generally have a good prognosis, though some face recurrence and have a lower survival rate despite treatment. Current prognostic factors for EC are still not able to accurately reflect disease prognosis. Therefore, the overall aim of the present project was to evaluate the impact of different, patient-specific factors on the prognosis of women with EC, with a special focus on the LRIG family of proteins, cadmium, dietary factors, daily routines, and the endometrial microbiome. Identifying these factors could pave the way for better determination of EC prognosis.

Study I analysed the role of LRIG1, LRIG2, and LRIG3 proteins on survival rates in women with EC. The analysis demonstrated that most patients had >50% positive cells for all three LRIG proteins. The LRIG1 protein score was high in most patients (97.3%). The percentage of LRIG3-positive cells was positively associated with better overall survival (P=0.019). There was no LRIG3 cell membrane staining in 30.4% of women who died, compared to 7.7% of EC survivors (P=0.01). Consequently, the results reveal a potential prognostic role of LRIG3, not LRIG1 and LRIG2, in EC. Study II assessed the role of cadmium intake on the survival of 416 women with EC residing in Sweden. Median dietary cadmium intake was 13.1 μg/day. High dietary cadmium intake was associated with lower overall survival (P=0.05), but not with progression-free survival (P=0.348). Accordingly, high dietary cadmium intake seems to be an adverse prognostic factor in EC. Study III evaluated the prognostic role of modifiable factors, such as dietary habits and daily routines, in EC using machine learning models. Among the 186 variables considered, consumption of sugar-sweetened beverages and fried potatoes increased the risk of EC recurrence and death, while physical activity decreased the risk of death. As a consequence, modification of specific dietary habits and daily routines might favourably impact EC prognosis. Study IV investigated the role of endometrial microbiota in women with EC and compared it to the bacterial profile of women with benign conditions of the gynaecological tract (endometrial hyperplasia, EH or endometrial polyp, EP). Most women in the EC and EH/EP groups were postmenopausal and had a BMI above the normal range. The median age in the EC group was 10 years higher than that in the EH/EP group. The preliminary analysis showed that patients with EC have endometrial microbiota distinct from that of patients with EH/EP: Atopobium and Porphyromonas were present in patients with EC, while Lactobacillus was present in those with EH/EP. Thereby, endometrial microbiota might play a role in EC prognosis.

To conclude, this thesis provides additional knowledge on certain molecular and nonmolecular factors that might play a role in EC, including its prognosis. Moreover, it emphasises the importance of continued investigation of other potential prognostic factors in EC.

List of scientific papers

I. RAZUMOVA Z, Oda H, Govorov I, Lundin E, Östensson E, Lindquist D, Mints M. The Prognostic Role of LRIG Proteins in Endometrial Cancer. Cancers (Basel). 2021;13(6):1361.
https://doi.org/10.3390/cancers13061361

II. RAZUMOVA Z, Govorov I, Östensson E, Mints M. Cadmium Intake as a Prognostic Factor in Endometrial Cancer: A Swedish Cohort-Based Study. Nutrition and Cancer. 2022;74(1):175-184.
https://doi.org/10.1080/01635581.2021.1883681

III. Wersäll OC, RAZUMOVA Z, Govorov I, Mints M. Dietary Habits and Daily Routines as Prognostic Factors in Endometrial Cancer: A Machine Learning Approach Nutrition and Cancer. [Submitted]

IV. Govorov I, RAZUMOVA Z, Andersson E, Mints M. Role of Endometrial Microbiota in Endometrial Cancer. [Manuscript]