It has been revealed in The Lost Experience that these six numbers are the core values of the Valenzetti Equation, a mathematical formula designed to predict the end of humanity. The numbers in actuality are said to represent human and environmental factors in the equation (given numerical form), though their precise meaning is uncertain.
When the Man in Black takes Sawyer to the Numbers Cave, he shows him names and numbers written all over the walls and ceiling. He explains that Jacob wrote these names and numbers -- that they represent people he brought to the island, as candidates to replace him. Each candidate's name is paired with a number.