Expression of INHBA in colorectal cancer and its relationship with microsatellite status and clinicopathological features / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the expression of INHBA in colorectal cancer and its relationship with microsatellite status and clinicopathological features.Methods:Bioinformatics analysis was conducted based on Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interaction Analysis (GEPIA) database, and the differentially expressed prognosis-related target genes in colorectal cancer were selected. Wax mass tissues of 107 patients with colorectal cancer who underwent surgery from January 2016 to June 2022 in the Third Affiliated Hospital of Jinzhou Medical University were collected, and the tissue microarrays were prepared. The clinicopathological microsatellite status [positive expressions of the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2 were mismatch repair proficient (pMMR), which represented low microsatellite instability or microsatellite stabilization; if any of these indexes was negative, it was judged to be mismatch repair deficient (dMMR), which represented high microsatellite instability] and INHBA expression in colorectal cancer tissues were detected by immunohistochemistry, data of the patients were retrospectively analyzed. The relationship between INHBA and microsatellite status as well as clinicopathological features was analyzed.Results:Three data sets of colorectal cancer were selected from GEO database: GSE110223 (13 cancer tissues, 13 paracancerous tissues), GSE110224 (17 cancer tissues, 17 paracancerous tissues), GSE113513 (14 cancer tissues, 14 paracancerous tissues), and the top 50 genes that were differentially up-regulated and down-regulated between cancer tissues and paracancerous tissues were screened. Intersection genes of 3 data sets were analyzed by Venn diagram, and 12 up-regulated genes and 17 down-regulated genes were screened out. According to GEPIA database, AQP8, ZG16 and INHBA genes among the up-regulated and down-regulated differential genes were associated with the prognosis of colorectal cancer. INHBA was higher expressed in colorectal cancer tissues than in paracancerous tissues (≥5 cm from the tumor margin) ( P < 0.05), and INHBA gene was selected for analysis. Immunohistochemical detection of collected colorectal cancer wax samples showed that the proportion of patients with high INHBA expression in colorectal cancer tissues was higher than that in paracancerous tissues [85.05% (91/107) vs. 67.29% (72/107), P < 0.05]. The high expression of INHBA in cancer tissues was related to the lesion site [right colon vs. left colon: 94.00% (47/50) vs. 77.19% (44/57)], maximum tumor diameter [>5 cm vs. ≤5 cm: 92.73% (51/55) vs. 76.92% (40/52)] and the depth of invasion [stage T 3-4 vs. stage T 1-2: 96.43% (54/56) vs. 72.55% (37/51)], differentiation degree [low and medium differentiation vs. high differentiation: 91.04% (61/67) vs. 75.00% (30/40)], lymph node metastasis [yes vs. no: 93.02% (40/43) vs. 78.13% (50/64)] (all P < 0.05), but had no correlation with age, sex, thrombus and nerve invasion (all P > 0.05). The proportion of patients with high expression of INHBA in colorectal cancer tissues in pMMR group was higher than that in dMMR group [93.22% (55/59) vs. 75.00% (36/48), χ2 = 6.91, P = 0.008]. Conclusions:INHBA is highly expressed in colorectal cancer tissues, and the highly expressed INHBA is closely related to clinicopathological features and microsatellite status of colorectal cancer. INBHA may be a new target for diagnosis, treatment and prognosis of colorectal cancer.