Saleem Saira, Aleem Iffat, Atiq Aribah, Tariq Sahrish, Babar Amna, Bakar Muhammad Abu, Syed Madiha, Maruf Maheen, Mahmood Mohammad Tariq, Zeshan Muhammad, Tahseen Muhammad, Hussain Raza, Loya Asif, Sutton Chris
Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7-A Block R-3, Johar Town, Lahore, 54000, Pakistan.
Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7-A Block R-3, Johar Town, Lahore, 54000, Pakistan.
Ecancermedicalscience. 2021 Mar 4;15:1197. doi: 10.3332/ecancer.2021.1197. eCollection 2021.
The aim of the study is to identify cornulin (CRNN) protein expression associated with advancement of tongue squamous cell carcinoma (TSCC). A comparison of addictive (containing potential carcinogens) versus non-addiction causative agents was expected to allow detection of differences in CRNN expression associated with TSCC. Bespoke tissue microarrays (TMAs) were prepared and immunohistochemistry (IHC) performed to determine the changes in CRNN expression in epithelial cells of node-negative (pN-), node-positive (pN+) TSCC and non-cancer patients' oral tissues. TMAs were validated by performing IHC on whole diagnostic tissues. Chi-square test or Fisher's-exact tests were used to establish significant expression differences. Analogous analyses were performed for biomarkers previously associated with TSCC, namely collagen I alpha 2 (COL1A2) and decorin (DCN) to compare the significance of CRNN. Keratinisation and its level (low, extensive) were studied in relation to CRNN so that the extent of squamous differentiation could better be assessed. IHC immunoreactive score (IRS) clustered the patients based on weak/moderate (Low (IRS ≤ +3)) or strong (High (IRS ≥ +4)) expression groups. A low expression was observed in a larger number of patients in control proteins COL1A2 (77.3%), DCN (87.5%) and target protein CRNN (52.3%), respectively. Low CRNN expression was observed in TSCC where nodes were involved (pN+: mean 1.4 ± 2.1) ( = 0.248). Keratinisation (%) was low (0% ≤ 50%) in 42.2% and extensive (1% ≥ 50.0%) in 57.8% patients. In conclusion, our study suggested that Low CRNN expression was associated with grade and lymph node metastasis in TSCC. CRNN expression is independent of addiction, however potentially carcinogenic addictive substances might be aiding in the disease progression.
本研究的目的是确定与舌鳞状细胞癌(TSCC)进展相关的cornulin(CRNN)蛋白表达。预计通过比较成瘾性(含潜在致癌物)与非成瘾性致病因素,能够检测出与TSCC相关的CRNN表达差异。制备了定制的组织微阵列(TMA)并进行免疫组织化学(IHC),以确定在淋巴结阴性(pN-)、淋巴结阳性(pN+)TSCC以及非癌症患者口腔组织的上皮细胞中CRNN表达的变化。通过对整个诊断组织进行IHC来验证TMA。使用卡方检验或Fisher精确检验来确定显著的表达差异。对先前与TSCC相关的生物标志物,即胶原蛋白Iα2(COL1A2)和核心蛋白聚糖(DCN)进行了类似分析,以比较CRNN的显著性。研究了与CRNN相关的角化及其程度(低、广泛),以便更好地评估鳞状分化程度。IHC免疫反应评分(IRS)根据弱/中度(低(IRS≤+3))或强(高(IRS≥+4))表达组对患者进行聚类。在对照蛋白COL1A2(77.3%)、DCN(87.5%)和靶蛋白CRNN(52.3%)中,分别观察到大量患者表达较低。在有淋巴结转移的TSCC中观察到CRNN低表达(pN+:平均值1.4±2.1)(P = 0.248)。42.2%的患者角化率(%)较低(0%≤50%),57.8%的患者角化广泛(1%≥50.0%)。总之,我们的研究表明,CRNN低表达与TSCC的分级和淋巴结转移相关。CRNN表达与成瘾无关,然而潜在致癌的成瘾物质可能在疾病进展中起作用。