SIP1蛋白表达或有助指示咽部鳞状细胞癌患者预后

  近日，来自东芬兰大学的研究人员通过研究指出，咽部鳞状细胞癌肿瘤中SIP1蛋白的表达或可帮助指示恶性肿瘤的发病阶段、癌症复发的风险及预后不良；基于研究结果，研究者表示，SIP1蛋白或许是一种有望在临床使用的新型预后因子，其可以帮助筛选出那些恶性肿瘤急需进行干预治疗的癌症患者。
  尽管咽部鳞状细胞癌（PSCC）是一种非常罕见的疾病，但其发生率在近30年里一直在上升，如今全世界大约有13万PSCC癌症患者，而且8万名患者已经死亡；最近有研究显示，人乳头瘤病毒（HPV）或许参与了口咽鳞状细胞癌的发生及预后，目前很多医院都会进行HPV的常规筛查，但是对于PSCC的生物标志物却一直没有建立。
  上皮间质转化（EMT）是一种复杂的细胞过程，其不仅对于胚胎发育至关重要，而且其在肿瘤进展过程中也处于激活状态，可以促进肿瘤细胞扩散，许多转录因子比如SNAI1， TWIST， SIP1， SLUG， 和ZEB1都是调节EMT过程的根本。
  本研究首次评估了EMT相关的转录因子在PSCC中扮演的角色，研究人员分析了肿瘤细胞、间质细胞及内皮细胞的细胞核中SNAI1， TWIST， SIP1， SLUG， 和ZEB1这5种转录因子的免疫组化表达，同时也对PSCC样本的细胞质中这5种转录因子进行了分析，目的在于评估临床病理学变量的表达和患者预后之间的关联。
  研究人员发现，上皮细胞SIP1免疫染色阳性的肿瘤具有更高的恶性程度，而且其更加容易向淋巴结转移，SIP1的表达和患者较差的5年生存期直接相关，而且SIP1是一种独立的预后因子。上皮细胞中SNAI1的表达可以预测患者生存率的下降及肿瘤尺寸的增加，然而间质细胞中TWIST的表达却和癌症的高复发率直接相关。最后研究者表示，本文研究对于揭示SIP1作为指示咽部鳞状细胞癌的预后非常重要，当然这或许也可以帮助开发治疗咽部鳞状细胞癌的新型疗法。（转化医学网360zhyx.com）
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Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression
BMC Cancer doi:10.1186/1471-2407-11-350
Anna Jouppila-Mättö123*, Mervi Närkiö-Mäkelä12, Ylermi Soini345, Matti Pukkila12, Reijo Sironen345, Hanna Tuhkanen345, Arto Mannermaa345 and Veli-Matti Kosma345
Background
Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT.
Methods
Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.
Results
Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).
Conclusion
TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.

SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma.
Histol Histopathol http://www.ncbi.nlm.nih.gov/pubmed/25412653
Jouppila-Mättö A1, Mannermaa A2, Sironen R2, Kosma VM2, Soini Y2, Pukkila M3.
Objectives: The epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis that enables tumor cells to invade and metastasize. The transcription factors SIP1, SLUG, ZEB1, SNAI1, and TWIST are fundamental in regulating EMT. We investigated the relationships between several clinicopathological variables, prognosis, and SIP1, SLUG, or ZEB1 in a retrospective pharyngeal squamous cell carcinoma (PSCC) cohort. Study Design: Immunohistochemistry was used to evaluate the expression of SIP1, SLUG, and ZEB1 in 108 tumor samples from a retrospective cohort of patients with PSCC. Results: Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p=0.02) and had more lymph node metastases (p=0.04) than SIP1-negative tumors. Tumors with positive stromal staining of SIP1 relapsed more often than SIP1-negative tumors (p=0.007). Negative SIP1 immunoreactivity correlated significantly with better disease-specific survival (DSS) and better overall survival (OS) (p=0.012 and p=0.003 for epithelial reactivity, p=0.018 and p=0.003 for stromal reactivity, respectively). Lack of epithelial SIP1 expression remained an independent and favorable prognostic factor in a Cox proportional hazards model (p=0.046), together with high Karnofsky performance status score and low T class (p<0.001 for both). Co-expression of SNAI1, TWIST, and SIP1 in tumor epithelium predicted even shorter DSS than SIP1 expression alone (p<0.001) in the present study cohort. Conclusions: SIP1 is related to cancer progression and appears to be an independent prognostic factor in PSCC.